The Current Status, Hotspots, and Development Trends of Nanoemulsions: A Comprehensive Bibliometric Review

Introduction

Nanoemulsions are two immiscible liquids with droplet diameters between 20 nm and 500 nm that are mixed and stabilized via suitable emulsifiers to create a two-phase dispersion system, including two-phase systems such as O/W and W/O nanoemulsions, as well as multiple nanoemulsions such as W/O/W.¹ Surfactants reduce the droplet size of the nanoemulsions by reducing the interfacial tension γ between the oil phase and the water phase. The dosage of surfactants required to produce the minimum droplet size depends on its activity concentration in bulk.² The extremely small size of nanoemulsions results in different characteristics from those of conventional emulsions,³ allowing for them to maintain kinetic stability for a long time, in addition to their high specific surface area, transparent appearance, and adjustable rheology. Owing to their unique properties, nanoemulsions have been widely used in various fields⁴ such as drug delivery,⁵ food,⁶ cosmetics⁷ and pesticides.⁸

In the pharmaceutical industry, owing to the hydrophobic structure inside the nanoemulsions, it can be used as a carrier for poorly soluble drugs, improving their solubility and bioavailability,⁹ reducing the first-pass effect of the liver, promoting the lymphatic transport and absorption of drugs, and facilitating better anti-inflammatory and antioxidant capabilities.¹⁰ Currently, it has been developed for oral administration,¹¹ dermal administration,¹² ocular administration,¹³ pulmonary administration,¹⁴ intranasal administration,¹⁵ and drugs such as cyclosporine¹⁶ and saquinavir¹⁷ have been approved for marketing in the form of nanoemulsions. In recent years, nanoemulsions have been widely studied in the areas of cancer treatment,¹⁸ RNA therapy,¹⁹ photodynamic therapy,²⁰ gene therapy,²¹ immunotherapy²² and vaccine adjuvants.²³ Shukla et al showed good efficacy in treating breast cancer bone metastasis by crystallizing self-assembled nanoemulsions into porous crystals of alendronate sodium and oleanolic acid, which prolonged the drug’s action time in the body and prevented bone loss while treating cancer.²⁴ Borrajo et al developed an ionizable nanoemulsions for RNA delivery. Compared with lipid nanoparticles, nanoemulsions can better overcome the blood‒brain barrier, exhibit good cell viability and transfection efficiency, and have greater diffusion properties.²⁵ Nanoemulsions can also be used in medical imaging treatments, such as the encapsulation of photosensitizer PSs in photodynamic therapy, which can reduce the tendency of PSs self-aggregation, increase permeability and retention, and improve the efficiency of photodynamic therapy.²⁶ Given the surface tunability of nanoemulsions, while drugs are encapsulated internally, they can also be modified with targeted fragments on the surface to achieve targeting.²⁷ Li et al modified paclitaxel and docosahexaenoic acid lipid nanoemulsions with folic acid, and the experimental results revealed increased cellular uptake rates, indicating synergistic effects in the treatment of breast cancer.²⁸ Nanoemulsions promote penetration and can be used as liquid droplets or sprays.²⁹ When used for topical administration to the skin, nanoemulsions easily penetrate the stratum corneum of the skin, promote the absorption of active ingredients, and have good compliance. Currently, people are more likely to make drugs into nanoemulsions-based hydrogel transdermal patches. Rai et al prepared nanoemulsions and polyvinyl alcohol hydrogel films from carbamazepine, which reduced the moisture content and moisture absorption rate and promoted skin permeability.³⁰

In the food industry, nanoemulsions are usually used to encapsulate and deliver nutrients such as fat-soluble vitamins,³¹ plant sterols,³² beta-carotene,³³ flavonoids,³⁴ and cinnamaldehyde³⁵ in food, which can increase their digestibility, encapsulation efficiency and bioavailability.³⁶ In addition, nanoemulsions can also be used for the preparation of biodegradable coatings, edible films,³⁷ and antibacterial coatings.³⁸ An essential oil nanoemulsions is a common preparation form. Essential oils are natural hydrophobic volatile ingredients with excellent antioxidant, anti-inflammatory, antibacterial, and insecticidal properties and are recognized as safe and effective.³⁹ Compared with conventional essential oils, essential oil nanoemulsions have better antioxidant properties⁴⁰ and antibacterial properties⁴¹ and are especially suitable for controlling microbial growth with essential oils. They can be used to deliver various natural substances with antimicrobial activity,⁴² extending their shelf-life. Researchers have made many natural products, such as carvacrol,⁴³ thyme oil,⁴⁴ peppermint oil and cinnamon oil⁴⁵ into essential oil antibacterial nanoemulsions, all of which show good antimicrobial activity. The nanoemulsions form can also mask the irritating taste and aroma of conventional essential oils⁴⁶ while reducing their impact on human health.⁴⁷ Essential oil nanoemulsions can also be used as natural food preservatives.⁴⁸ Yang et al prepared a sodium alginate/tea tree essential oil nanoemulsions containing TiO₂ nanoparticles, which showed good effects on postharvest quality assurance and prevention of anthracnose in banana fruit.⁴⁹

In the environmental protection industry, such as the manufacture and use of pesticides such as insecticides, the superior performance of nanoemulsions has gradually been revealed. Due to their high efficiency, safety and environmental protection characteristics, the number of studies on nanoemulsions in the environmental field is increasing. Researchers have made nanoemulsions insecticides from sulfoxaflor,⁵⁰ pyraclostrobin,⁵¹ cyhalothrin,⁵² and fennel essential oils⁵³ that are promising pesticides. Nasser et al prepared a new nanoemulsions insecticide using ginger essential oil and basil essential oil as raw materials to prevent white ant activity in Taiwan and proposed a sustainable and environmentally friendly natural plant-derived insecticide.⁵⁴ Gupta et al prepared and characterized a chitosan-encapsulated thyme oil and musk essential oil nanoemulsions and reported that it had control effects on various major mosquito species.⁵⁵ Environmental protection is a major goal that researchers have pursued. The future trend is to make more natural plant essential oils⁵⁶ into nanoemulsions forms for use as pesticides that are safer and more efficient, which can not only reduce costs and application amounts but also protect the environment to a greater extent.

The methods used to prepare nanoemulsions can be divided into two categories according to their energy consumption: high-energy methods and low-energy methods. High-energy preparation methods include high-pressure homogenization,⁵⁷ ultrasonic methods,⁵⁸ and microfluidization,⁵⁹ whereas low-energy preparation methods include the phase transition temperature method⁶⁰ and self-emulsification method.⁶¹ The high-energy method relies on the strong destructive force generated by mechanical devices, such as shear force, turbulence, cavitation, and ultrasonic disruption, to reduce size.⁶² The current method commonly used by researchers involves subjecting coarse emulsions to high-pressure homogenization followed by ultrasonic treatment. Palla et al used high-speed homogenization followed by ultrasonic treatment with a curcumin-loaded monoglyceride gel to prepare a nanoemulsions of gel oil particles, resulting in a nanoemulsions with at least 10 months of stability and high encapsulation efficiency.⁶³ Nonetheless, the high-energy methods for preparing nanoemulsions have high energy consumption and high cost and are not suitable for heat-sensitive products. Low-energy methods depend on the chemical energy stored in the system, such as the characteristics of surfactants, oils, and water systems, and require only slight agitation to achieve nanoemulsification. Alam et al used a low-energy emulsification method to prepare babchi oil nanoemulsions-based hydrogels and explored their therapeutic effects on psoriasis. The results revealed that the nanogel formulation had better drug permeability.⁶⁴ Low-energy emulsification methods are more convenient and energy efficient but require higher surfactant concentrations to stabilize nanodroplets. Moreover, more systematic research is necessary in the optimization of nanoemulsions formulations, such as investigation of the amount of surfactant used, the type of oil phase, and other factors. The degradation mechanism of nanoemulsions depends on its system compositions such as the type of oil phase, the type of surfactants, the relative concentration, the pH value, the ionic strength and the type of solvent, so its kinetic stability can be improved by the addition of stabilizers, such as emulsifiers, texture modifiers, weight enhancers or maturing agents.⁶⁵ At the same, as a model system, nanoemulsions can enhance the colloidal assembly of complex emulsion systems and the understanding of rheology.⁶⁶

The stability of nanoemulsions is also a popular topic among researchers. In addition to common instability mechanisms such as stratification, flocculation, and coalescence, Ostwald ripening is the main instability mechanism of nanoemulsions.^67–69 By increasing the amount of emulsifier or adding long-chain triglycerides, Ostwald ripening can be inhibited, and the stability of nanoemulsions can be enhanced, but this will inevitably affect safety performance, as commonly used emulsifiers such as the surfactants Tween⁷⁰ and Span⁷¹ often face limitations due to potential toxicity risks, which pose a threat to the safety of nanoemulsions products. Currently, researchers are developing new emulsifiers for nanoemulsions, such as plant proteins, whey protein, and soy protein concentrate.⁷² Saponins, such as glycyrrhizic acid,⁷³ camellia saponin,⁷⁴ and Q-Naturale,⁷⁵ are the most important class of natural emulsifiers due to their high surface activity, amphiphilicity, abundant sources, and low cost, which promote their use in commercial production.⁷⁶ There are also other natural polymers, such as gum Arabic,⁷⁷ maltodextrin,⁷⁸ and lecithin,⁷⁹ that can be used as natural emulsifiers. These natural emulsifiers are biocompatible, biodegradable, and environmentally friendly. Using them individually or in combination can achieve satisfactory results. Further exploration of their sources, production, emulsifying capabilities, and performance comparison is urgently needed to determine their future prospects.⁸⁰

At present, research on nanoemulsions has focused mainly on seeking more extensive applications, better stability, lower cost and larger scale preparation methods, and safer and more effective emulsifiers. To date, the literature reviews on nanoemulsions published have described their properties, preparation methods, stability, and applications individually or in one aspect, but there has been no comprehensive bibliometric review of nanoemulsions considering the countries/regions, hotspots, and development trends, now there is only one bibliometric review of the use of nanoemulsions and/or in-situ gels for ocular drug delivery systems during 2011–2021 by Fatimah et al. When researchers or institutions, including pharmaceutical, food, pesticide, and other companies or research institutes, seek a comprehensive overview of the current research hotspots of nanoemulsions, there is often a lack of relevant information, by conducting data mining and visualization analysis on a sufficiently large text dataset through bibliometrics, sorting out and summarizing certain indicators, the development history, research status and research hotspots in the field of nanoemulsions can be clearly revealed, providing reference value and significance for subsequent research. This study aimed to scientifically investigate global research progress in nanoemulsions research from 2013–2023 and analyze the literature considering different analytical standards and perspectives, with the aim of exploring further research hotspots and future development tendencies. Bibliometrics refers to the quantitative and visual analysis of published academic research in a specific field via mathematical and statistical methods. It can reveal subtle differences in the development of a particular field, as well as emerging hotspots in that field.⁸¹ Currently, it has been extensively applied across a wide variety of disciplines and industries, such as medical science,⁸² pharmaceutical sciences,^83–86 economics,⁸⁷ management science,⁸⁸ social sciences,^89–91 environmental sciences,^92,93 and materials science.^94–96 To this end, this study used bibliometric methods to conduct quantitative and visual analyses of the following aspects of nanoemulsions: 1) main contributing countries; 2) major contributing institutions; 3) common research fields; 4) the most productive journal; 5) keyword analysis; 6) the most prolific author; and 7) hot papers and highly cited Essential Science Indicators (ESI) papers. In addition, the research hotspots and future trends in the field of nanoemulsions are discussed.

Method and Data Handling

Data Collection

We selected the Web of Science (WOS) Core Database (version ©2024 Clarivate), which, owing to its rigorous journal selection, was used to discover researchers’ scientific outputs and disciplinary developments. Data were collected on March 18, 2024, through the WOS Database Citation Index Science Citation Index Expended (SCI-E) and Social Science Citation Index (SSCI) databases via the search strategy “nanoemulsions*” or “nano emulsion*” in the ‘subject’ field, with document types limited to ‘Article’ and ‘Review article’. The publication year was set from 2013–2023, resulting in a total of 8561 eligible publications after retrieval.

Data Input and Deduplication

The intact records of all acquired documents were downloaded and input into Derwent Data Analyzer (DDA) for processing and then classified according to the countries, institutions, research fields, journals, keywords, authors, and other field lists. In addition, for each item field set of the list, DDA employs an inherent cleaning tool that automatically removes duplicate data.

Data Partition and Merging

DDA software can perform data cleaning, multiview data mining and visual analysis. After the DDA software automatically processes duplicate items, the items still need to be manually confirmed, split and merged. For example, articles from England, Scotland, Northern Ireland and Wales were all counted as United Kingdom articles, whereas those from Hong Kong, Macao and Taiwan were incorporated into China’s articles. Additionally, articles from different campuses of the same university were grouped under a single article for that university.

Data Analysis and Visualization

After automatic and manual cleaning of the DDA data and matrix analysis, bubble charts, cluster maps and Sankey diagrams were drawn. Cluster maps can show the cooperative relationships between institutions, whereas bubble charts display the development trends in research fields, journals, and keywords, revealing useful information. The main areas of bibliometrics were also analyzed in the form of tables, such as countries/regions, institutions, research fields, journals, authors, highly cited papers and hot papers, while bibliometric indicators such as citations, average annual citations, and h-index, were used to study nanoemulsions from different perspectives. Moreover, some studies published online in advance usually have publication dates one to two years later. For a unified analysis, we set their publication year as that of online publishing.

Results

Number and Type of Publications

The 8561 papers acquired via the above search strategy were mainly research articles (7489; 87.48%) and comprehensive articles (1072; 12.52%). Some publications were not solely classified as research or review articles but also comprise other categories, such as conference proceedings papers (63; 0.74%), papers published online (52; 0.61%), withdrawn publications (15; 0.18%), book chapters (9; 0.10%), and publications expressing concern (1; 0.013%). The vast majority of the articles were published in English (8537; 99.72%), and the rest were published in Portuguese (11; 0.13%), Chinese (4; 0.047%), Japanese (3; 0.035%), Polish (2; 0.025%), German (2; 0.025%), Czech (1; 0.009%) and Serbo-Croatian (1; 0.009%).

The growth trend of the number of publications and citation frequency in the field of nanoemulsions research from 2013–2023 is described (Figure 1), including the proportions of research from China, USA, and India as the top three countries in terms of the number of publications. The number of publications on this topic increased from 285 in 2013 to 1142 in 2023 and is increasing annually. China was in the leading position in terms of the aggregate number of publications for most of the time. USA started research on nanoemulsions earlier, so it published the most articles from 2013–2016. Although research on nanoemulsions began lately in India, its growth momentum has been strong in the past three years, and the growth rate of research from India has exceeded that of USA.

Figure 1 Annual trends in the number of published articles related to nanoemulsions.

Number of Countries and Publications

A review of the 8561 publications related to nanoemulsions research shows that 110 countries have contributed to this field. The top 20 countries/regions in terms of the number of publications and citations are described (Table 1). Asia had the most countries/regions, with a total of eight, Europe had six, America had four, and Africa and Oceania each had one.

Table 1 The Top 20 Most Productive Countries/Regions in the Nanoemulsions Field

The three countries/regions that have made the largest contributions are China, USA and India. Since 2013, these three countries have published 1839, 1268 and 1248 articles, respectively, accounting for 21.5%, 14.8% and 14.6% of the total, far exceeding those of other countries and taking an absolute leading position. Brazil (862), Iran (621), Saudi Arabia (582), Egypt (463), Spain (370), South Korea (332), Italy (296), France (282) and Malaysia (269) are also highly productive countries. With respect to the impact of publications, the USA ranked first, with a total number of citations of 49,170; China ranked second, with 48,358 citations; and India ranked third, with 36,429 citations. The top three countries far outweighed Brazil, which ranked fourth, with 17,237 citations. To reflect the development of individual or collective research clearly, we also introduce the average number of citations per article (ACPP), which is calculated by dividing the total number of citations (TC) by the total number of publications (TP). USA ranked first with 38.78, followed by Italy (34.42) and Australia (32.22). The h-index was initially referred to as a simple quantitative indicator, defined as researchers who have published at least h articles and have been cited h times. To some extent, this reflects the research achievements of researchers.⁹⁷ Later, academic groups or institutions,⁹⁸ journals⁹⁹ and countries¹⁰⁰ also used the h-index to measure their collective research achievements.¹⁰¹ As shown in Table 1, USA ranked first with an h-index of 99 in this field. China and India followed closely behind, with h-indices of 92 and 83, respectively. The top three countries had significantly higher h indices than other countries did. Taking all the parameters into consideration, USA ranked first with an extremely high h-index and ACPP. China and India also had relatively high h-indices but only ranked in the upper middle range of the ACPP. However, given that their publication counts far surpassed those of other countries, publications from the USA, China, and India demonstrated the best average performance.

Country/Region Cooperation

In the DDA software, if an article is coauthored by two or more countries’ institutions, it is defined as an outcome of international collaboration.¹⁰² The existence of affiliations between research institutions with international collaborations was not considered. Among the top 20 productive countries, Pakistan ranked first, with a cooperation rate of 80.71%, followed by the UK (75.62%) and Saudi Arabia (75.08%). In general, European countries have higher rates of international collaboration, whereas Asian countries, with the exceptions of Pakistan and Saudi Arabia, generally have lower rates of collaboration. In addition, although the number and level of publications in China and India are relatively high, their degree of international cooperation is low.

An academic cooperation network diagram of the top 20 contributing countries was constructed via DDA software (Figure 2). DDA software draws network diagrams on the basis of the co-occurrence matrix. The size of a circle is related to the country’s relative contribution, and the lines between circles represent cooperation among countries. The thickness of the lines represents the frequency of cooperation. The results demonstrate that nine of the twenty countries have cooperation with other 18 countries, and seven countries have cooperation with all of the other nineteen countries, while Portugal and Australia have cooperation with only 16 countries, Malaysia with 15 countries, and Mexico with 14 countries (all the cooperation is limited to the top 20 contributing countries, cooperation with countries other than the top 20 is not included), and according to the thickness of the lines, it can be seen that cooperation between China and the United States is the most frequent, and Saudi Arabia has a close frequency of cooperation with other countries.

Figure 2 Collaboration matrix map of the top 20 most productive countries/regions.

Contributions of the Most Productive Institutions

The total number of research institutions that have conducted research on nanoemulsions is 5067, and the top 20 research institutions were defined (Table 2). Among the top 20 institutions, four are from Brazil; three each from Saudi Arabia, Iran and China; two each from Egypt and Portugal; and one each from USA, India and Malaysia. In terms of research volume, the University of Massachusetts ranked first, with 275 publications, far exceeding those of other research institutions. This was followed by King Abdulaziz University (187) and Islamic Azad University (178). Among them, Gorgan Univ Agr Sci & Nat Resource had the best ACPP, with a score of 65.85, followed by the University of Massachusetts (65.25) and Jiangnan University (41.91). The University of Massachusetts in USA was at the top of all institutions with the most publications (275), the highest ACPP (65.25), and the highest h-index (76). It also contributed significantly more than other countries did.

Table 2 The Top 20 Most Productive Institutions in the Nanoemulsions Field From 2013–2023

The collaboration network among the top 15 institutions with the most contributions from 2013–2014 is illustrated (Figure 3). This collaborative network provides an intuitive perspective of cooperation between different institutions, which can help identify more beneficial collaborations. The number of publications is listed near the name of each institution and yellow cross points between institutions indicate cooperation with other research institutions. The yellow dots indicate the outputs and intensity of collaboration among institutions. The node data without intersections represent the number of publications published by the research institution, which may be independent research or collaboration with other institutions except the top 15. That King Abdulaziz Univ has built the largest collaborative network, followed by King Saud Univ and Prince Sattam bin Abdulaziz Univ (Figure 3). In terms of the number of collaborations, University of Massachusetts and King Abdulaziz Univ had the highest collaboration counts, with 59 articles, followed by Islamic Univ and Tehran Med sci Univ, as well as King Saud Univ and Prince Sattam bin Abdulaziz Univ. In addition, research in the field of nanoemulsions by Sao Paulo Univ, Fed Rio Grande do Sul Univ and Fed Rio de Janeiro Univ is relatively independent.

Figure 3 DDA cluster map of the cooperation of the top 15 institutions.

Contributions to Leading Research Fields

The analysis of research fields indicates the application direction of nanoemulsions. Research on nanoemulsions covered 87 different research fields, and the 20 most productive research fields with the highest number of publications are summarized (Table 3). “Chemistry” ranked first with 2885 articles, followed by “Pharmacology and Pharmacy” (2138) and “Food Science and Technology” (1952), which far surpassed other research fields in terms of the number of publications. The top three research fields in the ACPP ranking are “acoustics” (48.81), “nutrition” (39.12), and “food science and technology” (35.13). The literature in the field of acoustic research is related mainly to the preparation of nanoemulsions via ultrasonic emulsification. For example, Ghosh et al used ultrasonic emulsification to prepare basil oil nanoemulsions and characterized their antibacterial activity.¹⁰³

Table 3 Contributions of the Top 20 Research Areas in the Field of Nanoemulsions

A bubble chart of the 20 most productive nanoemulsions research fields is shown (Figure 4). The bubble chart depicts the growth tendency of research fields over time through horizontal changes in bubble size in three dimensions: research field, publication year, and number of publications. The vertical change in bubble size and the number within the bubbles represent the number of publications in various research fields for that particular year. Research achievements in most related fields are growing annually, with the number of research papers in environmental science and ecology increasing from 1 in 2013 to 34 in 2023, a 33-fold increase, indicating that breakthroughs have been made in this field, mainly due to extensive research on nanoemulsions pesticides.¹⁰⁴

Figure 4 Bubble chart of the top 20 nanoemulsions research areas by year.

The differences in research directions between 2013–2023 and 2021–2023 were compared (Table 4). Except for the fact that most research directions have maintained their publication numbers, “Environmental Science and Ecology” has seen a significant increase in its ranking. In addition, “Plant Sciences” and “Entomology” have entered the top 20 research directions over the past three years.

Table 4 Comparison of the Nanoemulsions Research Areas in 2013–2023 and 2021–2023

Main Contributing Journals

Research on the primary contributing journals can help researchers of nanoemulsions more clearly decide which journal is the best choice for submission of their reports. From 2013 to 2023, a total of 1211 journals published 8561 papers related to nanoemulsions, and the total number of papers in the top 20 journals was defined (Table 5). Food Chem. ranked first with 222 papers, followed by Pharmaceutics (221, J). Drug Delivery Sci. and Technol. (213), and Int J. Pharmaceutics (210). With respect to total citations (TCs), Food Hydrocolloids was cited 11,934 times in the past decade in nanoemulsions research, ranking first, followed by Food Chem. (10,650) and Int. J. Pharmaceutics (6696). For the ACPP, Food Hydrocolloids still ranked first at 68.19 times, followed by J Agric. and Food Chem. (52.06) and Food Chem (47.97). A journal’s impact factor is calculated by dividing the total number of citations to all publications in that journal over the previous two years by the number of publications.¹⁰⁵ As shown in Table 5, the ACPP of all journals’ papers on nanoemulsions were greater than their own IF, which fully reflects researchers’ strong interest in the research of nanoemulsions. With respect to the impact factor, Food Hydrocolloids had the highest impact factor of 10.7 in 2022, followed by Food Chem. (8.8) and Int J. of Biol. Macromolecules (8.2), Food Res. Int. (8.1) and Int J. Nanomed. (8.0).

Table 5 Top 20 Journals Publishing Studies in Nanoemulsions

A bubble chart of the top 20 journals publishing papers on nanoemulsions is shown (Figure 5). The bubble chart reveals that Pharmaceutics did not publish any articles before 2017, with only 2 articles published in 2017, but reached 72 articles in 2022, ranking second among all the journals and growing 35-fold. Int. J. Biol. Macromolecules had only 2 articles in 2013 but reached 43 articles in 2023, a 20-fold increase. Drug Delivery reached a peak of 19 articles published in 2016. Most journals reported a peak in articles on nanoemulsions research from 2021–2023.

Figure 5 Bubble chart of the top 20 journals publishing papers on nanoemulsions.

Contributions of Leading Authors

The study of the contributions of leading authors can promote exchanges and collaborations among scholars interested in nanoemulsions research. Within our analysis scope, 29,769 authors contributed to nanoemulsions research, and the 20 most productive authors by number of publications are displayed (Table 6. Among these 20 authors, 6 are from Brazil, 4 each are from Saudi Arabia and Spain, 2 each are from India and the USA, and 1 each is from France, Iran, and Malaysia. Among the 4 authors from Saudi Arabia, 3 are from King Saud University, and 2 each are from Massachusetts Univ (USA), Federal do Rio Grande do Sul Univ (Brazil), Lleida Univ (Spain), Jamia Hamdard Univ (India), Sao Paulo Univ (Brazil), and Federal do Amapa Univ (Brazil).

Table 6 Contributions of the Top 20 Authors in Nanoemulsions Research

McClements, DJ ranked first, with 248 publications, far exceeding those of other scholars, indicating his significant contribution to this research area. Teixeira, HF ranked second with 71 publications, and Shakeel, F ranked third with 54 publications. In terms of the ACPP, Trujillo, Laura Salvia ranked first with 89.56, followed by Jafari, SM (79.98), McClements, DJ (70.86), and Martin-Belloso, O (68.79). With respect to the h-index, McClements, DJ ranked first with a score of 76, far surpassing other scholars, followed by Jafari, SM (35), Xiao, H (29), Ali, J (24), Baboota, Sanjula (24), and Salvia-Trujillo, L (24). There are two limitations in comparing the h-indices of scholars.¹⁰⁶ First, the h-index only increases or remains constant over time, so it cannot indicate whether a scholar is still active in their academic career. Second, older scholars who entered the academic field earlier have an advantage in the h-index compared with younger scholars.

Research Hotspots and Tendencies

To better understand the research hotspots and tendencies of nanoemulsions, the author keywords, hot papers, and highly cited papers from 8561 articles were analyzed. These research topics were sourced from databases such as the SCI-E and SSCI of the Web of Science.¹⁰⁷ ESI hot papers were defined as papers published globally in the last 2 months with high citation frequency. Highly cited papers were defined as research in the same discipline that ranks in the top 1% of citation frequency within the 10-year range included in the ESI.

Author Keyword Analysis

Author keywords can provide valuable information on research-related topics, making them a focus of widespread attention among scholars.¹⁰⁸ A total of 14,310 author keywords were obtained by representing keywords with similar meanings in a unified term. Notably, publications without author keywords were not included in the statistics. Among the 8561 articles, the 30 most common author keywords are displayed in a bubble chart (Figure 6). The top 30 keywords comprise several main categories, including terms representing nanoscale particles: “nanoemulsions”, “nanoparticles”, “solid lipid nanoparticles”, “liposomes”, “nanocarriers”, and “nanomedicine.” In addition, keywords such as “essential oil”, “curcumin”, “chitosan”, and “beta-carotene” indicate common application areas and encapsulating materials of nanoemulsions. Furthermore, research on the properties of nanoemulsions, mainly related to “bioavailability”, “stability”, “antioxidant activity”, “antimicrobial activity”, “cytotoxicity”, and “antibacterial activity”, is also prominent. Common preparation methods for nanoemulsions, such as “ultrasonication”, “high-pressure homogenization”, and “microfluidization”, also have high frequencies. As the third highest-frequency keyword, “essential oil” had fewer publications before 2016, with only 9 articles in 2016. However, in 2017, 23 articles were published, and the trend continued to grow, reaching a peak of 93 articles in 2022. This growth is attributed mainly to the extensive research and application of nanoemulsions containing essential oils in the food industry because of their antimicrobial and antioxidant characteristics. For example, Erfani et al prepared a nanoemulsions containing cinnamon essential oil encapsulated in beta-cyclodextrin and sodium caseinate, resulting in a longer storage time.¹⁰⁹ Restrepo et al prepared nanoemulsions containing lemongrass and rosemary essential oils incorporated into edible films, which were shown to increase the breathability, transparency, and extensibility of the films.¹¹⁰ Many essential oils have been formulated into nanoemulsions, such as lemon oil,¹¹¹ lavender oil,¹¹² marigold oil¹¹³ and patchouli leaf oil,¹¹⁴ which exhibit superior performance.

Figure 6 Bubble chart of the top 30 author keywords by year.

In the pharmaceutical industry, research on nanoemulsions in the drug delivery field has been increasing annually. For example, Abdulaal et al reported the preparation and formulation optimization of sodium alendronate nanoemulsions for in situ injection for the treatment of osteoporosis in 2023. Compared with traditional oral dosage forms, the phase separation injectable sodium alendronate nanoemulsions exhibited sustained and controllable drug release.¹¹⁵ El Makawy et al prepared quinoa oil-alginate nanoemulsions showing anticancer activity against breast cancer, inhibiting the further development of breast cancer.¹¹⁶

According to the keyword “curcumin”, curcumin is commonly encapsulated in nanoemulsions. Curcumin has multiple pharmacological actions, such as anticancer, anti-inflammatory, and antioxidant effects.¹¹⁷ It is also an important natural edible pigment in the food industry that is safe and nontoxic. It has wide applications in many industrial fields, such as medicine,¹¹⁸ textile dyeing,¹¹⁹ and feed.¹²⁰ Nonetheless, owing to its poor water solubility, chemical stability, and oral bioavailability,¹²¹ its application is often limited. Studies have shown that encapsulating curcumin in nanoemulsions can improve its dispersibility and chemical stability due to the extremely small droplet size, providing more possibilities for drug delivery routes, regulating its release, promoting interaction with biological membranes, and improving bioavailability¹²² to promote its application. Ghanimatda et al prepared a curcumin nanoemulsions that showed therapeutic effects on cystic hydatidosis.¹²³ Ganta et al encapsulated paclitaxel and curcumin in a nanoemulsions containing linseed oil to treat ovarian cancer, which effectively enhanced the apoptotic response.¹²⁴ Yu et al prepared a curcumin nanoemulsions using a curcumin organic gel as the oil phase, which resulted in a significant increase in oral bioavailability and achieved the oral delivery of poorly soluble nutrients.¹²⁵

The top five keywords used in each of the 20 countries that have contributed the most to the nanoemulsions field are displayed (Table 7). Unsurprisingly, “nanoemulsions”, “nanoparticles”, “essential oils” and “bioavailability” are the most commonly used keywords in these countries. In addition to the use of nanoemulsions and emulsion as key words, among the top three countries contributing to the ranking, China has primarily studied stability, bioavailability and curcumin; USA has studied nanoparticles, bioavailability and stability; and India has studied bioavailability, nanoparticles, nanogels and essential oils. Additionally, many studies have been conducted on the preparation technology of nanoemulsions in Malaysia, as reflected by the use of “response surface methodology” and “high-pressure homogenization”, such as for the preparation of aspirin nanoemulsions via response surface methodology¹²⁶ and the preparation of polycarboxylate nanoemulsions via high-pressure homogenization.¹²⁷ Germany has conducted more research on lipid nanoparticles, and two of the top five keywords used are related to lipid nanoparticles; comparative studies between nanoemulsions and lipid nanoparticles have also been conducted.¹²⁸ In addition, “inflammation” is also the only keyword that appeared in the top five keywords of Germany among the 20 countries, reflecting the importance attached to it.¹²⁹

Table 7 Top 5 Most Used Author Keywords by the Top 20 Most Productive Countries

The Sankey diagram shows the flow relationships between the top ten institutions and the ten key words related to nanoemulsions (Figure 7). The results show that most of the top ten institutions have some knowledge of these ten key words, and most research has focused on key words related to nanoemulsions such as “drug delivery”, “cytotoxicity”, “curcumin”, “carotene”, “stability” and “antioxidants”. The Univ Sao Paulo, Univ Putra Malaysia and Univ Fed Rio Grande do Sul focused on drug delivery research, Natl Res Ctr and King Saud Univ focused on cytotoxicity research, Jamia Hamdard and King Abdulaziz Univ focused on curcumin research, Jiangnan Univ focused on β-carotene research, Massachusetts Univ focused on stability and β-carotene research, and Islamic Azad Univ focused on antioxidant research.

Figure 7 Sankey chart of the top 10 institutions.

Analysis of Hot Research Papers

The number of citations is an important indicator reflecting the impact of a study. According to our definition of hot papers, six such papers were identified and presented (Table 8). Notably, this article took the top-ranked authoritative institution as a representative and displays corresponding institutions. Among the six articles, four are review articles, and two are research articles. Sneha et al introduced the preparation of nanoemulsions and their progress in food applications.¹³⁰ Zhang et al reviewed the use of lipid carriers for mRNA delivery, including the application of nanoemulsions in mRNA delivery.¹³¹ Karimi-Maleh et al introduced research on Mof pesticides in sustainable agriculture and reduction of environmental hazards.¹³² Nanopesticides overcome the shortcomings of traditional pesticides and have become a promising alternative. Phatale et al researched advanced drug delivery methods to overcome the skin barrier.¹³³ Nanoemulsions constitute a new strategy for effective transdermal drug delivery. Haddadzadegan et al reviewed the oral delivery technology of therapeutic peptides and proteins, such as oil-in-water nanoemulsions, using lipid-based nanocarriers.¹³⁴ Philip et al conducted magnetic nanofluid research in which a nanoemulsions was used as a model system for magnetic nanofluids and reviewed its applications in various aspects.¹³⁵ The above studies focused on the application of nanoemulsions in the drug delivery, food, agriculture and environmental industries. In terms of the scholars’ countries, three are from India, two are from China, and one is from Australia.

Table 8 ESI Hot Citation Studies From 2013–2023

Research Analysis of Highly Cited Papers

The top 20 cited articles from the 8561 nanodispersion articles collected in this study were analyzed, and the specific publication information was collected (Table 9). Among the 20 articles, 11 were review papers and 9 were research papers. USA and India each contributed six papers, significantly surpassing other countries. China contributed three papers, Spain two, and the Netherlands, Australia, and Italy one each. Gupta et al summarized the formation, characteristics and applications of nanoemulsions, and had the highest total number of citations.⁶⁶ The article with the highest average number of citations per year was published in Nature Communications in 2018 by Wan et al, who provided a simple method for preparing thin-film composite nanofiltration membranes with polyamide layers, which is highly important for seawater desalination and sewage treatment.¹³⁶

Table 9 Top 20 Most Highly Cited ESI Publications From 2013–2023

Three of the 20 highly cited articles are related to nanopesticides. Kah et al conducted research on nanopesticides in 2014, mainly exploring formulations of related nanoemulsions.¹⁴⁵ In 2017, Prasad et al reported that nanotechnology can improve food quality and safety, such as the application of nanoemulsions to ice cream to improve its texture and uniformity and the ability to control the amount of pesticide sprayed and reduce the loss of nutrients during fertilization in agricultural fields.¹⁴⁶ Kumar, S. reported in 2019 that the nanoencapsulation of pesticides can result in controlled release characteristics, which can effectively improve the permeability, stability, and solubility of pesticides, and looked forward to the development of nanoemulsions pesticides.¹⁴⁷

In terms of medical applications, in 2016, Song et al reported the good biocompatibility and high oxygen solubility of perfluorocarbons (PFCs), such as PFC nanoemulsions, as ultrasound-triggered tumor-specific oxygen delivery oxygen shuttles to regulate the hypoxic microenvironment of tumors.¹⁴⁸ Anselmo et al synthesized PEG hydrogel nanoparticles with adjustable elasticity via nanoemulsions technology in 2015 and determined the effects of the elasticity of the nanoparticles on their blood circulation, phagocytosis, endocytosis, and targeting.¹⁴⁹ Lu et al studied the use of polymeric micelles and alternative nanocarriers to solubilize poorly soluble drugs in 2013. For example, nanoemulsions can be administered in various ways, such as oral, ocular, sublingual, or intranasal, and are characterized by high drug loading and high bioavailability. The disadvantage of these methods is that they often lack stability and are prone to flocculation and coalescence.¹⁵⁰

With respect to food applications, Salvia-Trujillo et al reported in 2013 the effects of the particle size of emulsions and nanoemulsions on lipid digestion and the accessibility of β-carotene, providing valuable knowledge for the development of carotenoid-based delivery for food and pharmaceutical applications.¹⁵¹ Acevedo-Fani et al prepared nanoemulsions with thyme, lemongrass or sage oils as the dispersed phase and sodium alginate solution as the continuous phase by microfluidization to prepare edible films. The physicochemical and antibacterial properties were also characterized.¹⁵²

The 20 highly cited articles not being mentioned are cited in Table 9.^137–144

Discussion

The main goals of this bibliometric research were to determine the trends in the literature on nanoemulsions research; identify countries/regions, institutions, authors, author keywords, hot papers, and highly cited papers; and summarize the current status, hotspots, and changing tendencies of the nanoemulsions field. Nanoemulsions, as biphasic dispersed systems with droplet sizes at the nanoscale, provide a platform for dissolving poorly soluble drugs and various hydrophobic compounds, enabling the delivery of a variety of substances. They have found widespread applications in many industries and fields and have become among the more advanced carrier delivery systems in pharmaceutical, food, cosmetic, and agricultural products. On the basis of an extensive bibliometric analysis, this study aimed to provide more fertile ground for new topics in the technology and application of nanoemulsions.

Pharmaceutical Science

As an effective drug delivery system, extensive research has shown that, compared with other drug administration systems, nanoemulsions have better patient compliance and greater health benefits, effectively protecting the delivery of hydrophobic drugs and improving bioavailability. According to the keyword analysis, nanoemulsions are widely used as drug delivery systems for hydrophobic drugs, and research on their properties is the most prevalent, with a particular focus on studies of bioavailability, pharmacokinetics, and cytotoxicity when used as nanopharmaceuticals. Nanoemulsions can significantly improve drug release profiles and bioavailability when administered through different routes. The mechanism of their ability to increase bioavailability is due primarily to their lipid-based delivery system, which can increase the solubility and stability of lipophilic drugs. Their small size can also increase drug penetration and retention, especially when used as a transdermal drug delivery system.¹⁵³ For use of quercetin as an oral drug, Mahadev et al prepared a quercetin nanoemulsions via an ultrasound method, and the results revealed that the bioavailability and therapeutic effect on diabetes in diabetic rats were greatly improved.¹⁵⁴ In addition, researchers have prepared oral nanoemulsions forms of 5-fluorouracil,¹⁵⁵ piperine,¹⁵⁶ β-carotene,¹⁵⁷ and rutin.¹⁵⁸ Their successful development has improved the bioavailability of drugs. For use as a nasal drug delivery carrier, Diedrich et al prepared a chitosan-coated nanoemulsions containing luteolin for nasal administration to treat neuroblastoma. The results revealed that its permeability increased by a factor of 6, the pharmacokinetic evaluation half-life increased by a factor of 10, the biodistribution increased by a factor of 4.4, and the bioavailability increased.¹⁵⁹ Researchers commonly evaluate the pharmacokinetics and pharmacodynamics of drugs encapsulated in nanoemulsions. The main research topics include the in vivo half-life, biological distribution, area under the blood concentration-time curve and maximum drug concentration.¹⁶⁰ To explore the degree of improvement in bioavailability of nanoemulsions, these studies are indispensable. Extensive studies have shown that making drugs into nanoemulsions can reduce their cytotoxicity^161–163 because nanoemulsions are not only mild in formulation but also have slow release characteristics, a small droplet size and a high dispersion coefficient, which can reduce drug accumulation, thus alleviating the toxic side effects of drugs.

Given the impact of the novel coronavirus, the prevalence and mortality of the COVID-19 pandemic have increased significantly.^164,165 Owing to the increasing prevalence of bacteria resistant to natural or synthetic antibiotics,¹⁶⁶ infections caused by multidrug-resistant bacteria have become a serious public health problem. Antibiotic resistance has become a health issue of global concern. To some extent, conventional antibiotic treatment has been unable to meet people’s antibacterial needs. Improving the delivery system of antibacterial drugs is an effective means to solve this problem. In recent years, interest in the antibacterial properties of nanoemulsions has increased. Whether it is a nanoemulsions encapsulating essential oils with antibacterial activity, the surfactant used in the preparation process, or the inherent antibacterial properties of the nanoemulsions, the main manifestation is the destruction of the lipid membrane of pathogens,¹⁶⁷ resulting in synergistic antibacterial effects and good therapeutic effects. The small spherical size of nanoemulsions droplets can prolong their retention at the lesion site and improve the antibacterial effect of drugs, and nanoemulsions antimicrobial therapy has good biocompatibility and spectral activity,¹⁶⁸ making it a promising carrier for COVID-19 treatment.^169–171 Moreover, the structure and function of nanoemulsions are adjustable and multifunctional, which makes them broadly applicable, such as for use as vaccine adjuvants¹⁷² and for the development of new drug delivery methods. The surface adjustability, high loading capacity, safety, and slow-release characteristics of nanoemulsions particles¹⁷³ can be utilized to encapsulate antiviral drugs such as COVID-19 vaccines¹⁷⁴ and antibacterial drugs, which have great application prospects. Emulsions have been used as safe delivery platforms for vaccines.¹⁷⁵ Targeting viruses through epitopes or targeted fragments displayed on the surface of nanoemulsions droplet particles or modifying phospholipids with polyethylene glycol can effectively prevent the phagocytosis of macrophages, allowing for drugs to achieve long-term circulation effects in the body,¹⁷⁶ resulting in improved therapeutic effects. In terms of structural modification, the preparation of multiphase emulsions can make them more complex and result in a potentially a wider range of applications. The multiple internalized phases of multiphase nanoemulsions can achieve various chemical zones to control the release of active ingredients and complex particle templates.¹⁷⁷ The chitosan-modified multiphase nanoemulsions prepared by Malik et al enhanced the permeability of the stratum corneum when applied to the skin, significantly improving the permeability and retention of drugs and enhancing the efficacy of skin infection treatment.¹⁷⁸ The complex structure of multiphase nanoemulsions also leads to harsh preparation conditions and limitations in large-scale production. In addition, the limitations of encapsulation efficiency and the preparation of multiple nanoemulsions inevitably lead to an increase in droplet size. Maintaining a small droplet size while maximizing the encapsulation efficiency of the contents is an area of great expectation and concern. As a drug delivery carrier, further characterization of the physicochemical properties of the prepared nanoemulsions are necessary, and many basic studies are needed to conduct pharmacological and toxicological evaluations as well as in vivo tests to minimize their toxic side effects.

Food Science

According to keyword list 6, the antibacterial and antioxidant capabilities of nanoemulsions are of greatest concern to food experts. There are five related words in the top 30 keywords, indicating their importance. As the demand for healthy, safe, green and natural products is increasing daily, consumers are increasingly inclined to choose foods that contain no or few synthetic additives.¹⁷⁹ In addition, there is also a growing demand for food products with better microbial safety and freshness. Therefore, developing new types of food preservatives to inhibit the growth of bacteria and microorganisms is an area of current research interest among researchers.¹⁸⁰ Nanoemulsions have shown great potential in preserving basic foods such as meat or vegetables. As natural antimicrobial and antioxidant agents, they can replace synthetic additives while ensuring the biological activity of ingredients and lengthening the shelf-life of food. Essential oil nanoemulsions and chitosan nanoemulsions¹⁸¹ have shown great application prospects in food preservation, especially in extending the shelf-life of muscle foods and the storage period of grains. Nonetheless, there is still much room for improvement in properly addressing the impact of essential oil additives or essential oil coatings¹⁸² on food flavor and sensory perception and exploring the mechanism of chitosan more clearly. There is also room for improvement in proposing valuable research results for the scientific community. Additional in vitro experiments and more powerful technical support are needed to develop nanoemulsions as food additives with daily maximum intake and recommended intake levels. More in vivo studies should be conducted to clarify their interactions with biological systems in the human body and their digestion and absorption mechanisms in the gastrointestinal tract.¹⁸³ Therefore, it is necessary to explore the bioaccumulation of compounds and the storage and excretion of metabolites and establish consumer confidence¹⁸⁴ to promote and expand the benefits and potential of nanoemulsions in food applications.

Essential oil nanoemulsions have great applications in the food industry, as essential oil nanoemulsions not only possess the powerful antibacterial,¹⁸⁵ antiviral and antifungal¹⁸⁶ properties of essential oils but also have better dispersibility,¹⁸⁷ stronger bioactivity and better sensory properties.¹⁸⁸ The wetting ability of surfactants and emulsifiers also helps enhance the antibacterial activity of essential oil nanoemulsions¹⁸⁹ and has the least impact on the sensory properties of the product, thus broadening their applications in many products. Furthermore, studies have reported that combining essential oil nanoliposomes with vacuum packaging can further increase their antibacterial activity, which has great potential.¹⁹⁰ Although the use of nanoemulsions as a delivery method to encapsulate hydrophobic drugs, essential oils, etc, has shown good advantages, as food additives, the safety and toxicological evaluation of nanoemulsions is indispensable. The use of essential oil nanoemulsions as alternatives to traditional chemical preservatives is still in the early stages of exploration and application, and relevant technologies, regulations and policy support are not yet fully established.¹⁹¹ The use of commonly used emulsifiers such as ionic surfactants¹⁹² and nonionic surfactants¹⁹³ poses a great threat to the safety of nanoemulsions. Therefore, while preparing nanoemulsions, it is necessary to improve relevant research ideas, change the current commonly used surfactants to develop new surfactants, further characterize their physicochemical properties, support research on the effects of surfactants on the particle size and stability of nanoemulsions with more numerical and model support, investigate new combinations and optimize new formulations,¹⁹⁴ reduce costs, and ensure safety to a greater extent. Better preservation and improvement of the characteristics and stability of nanoemulsions antibacterial agents requires more innovative methods and strategies.¹⁹⁵ In addition, there is an urgent need for safer, more widely applicable natural emulsifiers and more advanced preparation techniques, with a greater focus on their synergistic effects and mechanisms of action, to ensure the safety and effectiveness of nanoemulsions and meet the requirements in more scenarios. Furthermore, the content and purity of natural emulsifiers are difficult to standardize because of differences in their source plant growth areas, developmental stages, collection sites, and collection times. The standardization and industrialization of their development is also an urgent problem that needs to be addressed.

Agricultural Science

In the field of agriculture, in terms of research direction, the great application potential of nanoemulsions is reflected mainly in the direction of plant science and entomology, owing to their application in the transportation of nutrient fertilizers,¹⁹⁶ pesticides and insecticides during agricultural planting. A nanoemulsions is a surfactant-stabilized oil‒water two-phase dispersion that can increase the solubility and bioavailability of fertilizers, and the droplet size is very small; thus, the use of a nanoemulsions in plant and pest treatment can more easily penetrate the plant tissues and the cuticles of pests.¹⁹⁷ Owing to their relatively high specific surface area, encapsulating pesticides in nanoemulsions can better utilize the active ingredients and directly deliver them to the site of action, reducing the amount of pesticide used and minimizing their impact on the environment.¹⁹⁸ In addition, encapsulating nutrients such as various fertilizers, nutrients, and minerals in droplets is also more conducive to plant absorption and utilization, improving the health status and productivity of the plant and preventing fertilizer loss due to runoff or leaching.¹⁹⁹ This approach can improve plant efficiency and play an important role in agricultural planting. The application prospects of nanoemulsions in agriculture are gradually expanding. The development of new advanced nanoemulsions carriers, such as plant growth regulators,²⁰⁰ growth hormones,²⁰¹ antibacterial agents and biological pesticides,²⁰² will be beneficial for the efficient, innovative and sustainable development of entire agricultural field.

Energy Science

Owing to the depletion of fossil fuels and the reduction in harmful emissions from diesel engines, scientists have been searching for new fuels as replacements.^203–206 Biodiesel, such as pure lemongrass oil,²⁰⁷ safflower seed oil,²⁰⁸ and apricot seed oil,²⁰⁹ has shown good potential for energy conservation and emission reduction. The application of nanoemulsions in the energy field has focused mainly on reducing the exhaust emissions of biodiesel and improving the oil and gas recovery efficiency.²¹⁰ Kumar et al studied the performance of diesel engines fueled by waste orange peel oil nanoemulsions. The results showed that at maximum power output, compared with those of pure orange oil biodiesel fuel, the peak cylinder pressure and heat release rate of orange oil biodiesel nanoemulsions fuel increased.²¹¹ Research indicates that the aqueous phase in diesel emulsions can reduce combustion temperatures and lower harmful emissions from diesel engines.²¹² Water increases the kinematic viscosity and calorific value of fuel.²¹³ Biodiesel nanoemulsions not only increase combustion efficiency but also significantly reduce emissions of nitrogen oxides such as CO and NOx, as well as sulfur oxides, minimizing environmental harm. In the future, optimizing the economic and formulation aspects of biodiesel nanoemulsions will be a key focus of research.²¹⁴ In terms of oil and gas recovery, the surfactant in the nanoemulsions accumulates more around the oil core, and the free surfactant molecules in the continuous phase decrease, thus reducing the loss caused by the adsorption of surfactant on the rock surface during oil and gas recovery.²¹⁵ Wei et al prepared a series of surfactant-stabilized oil-in-water nanoemulsions and conducted imbibition tests on tight cores compared with saline water. The results showed that nano-oil droplets can promote the ultimate recovery of crude oil.²¹⁶ The mechanism by which nanoemulsions enhance oil recovery is manifested mainly in the emulsification of crude oil, which reduces the interfacial tension between oil and water through surfactants, reverses wettability, and expands the swept area.²¹⁵ Nonetheless, there is still a lack of clarification of its adsorption characteristics and diffusion behavior, which requires further research. In addition, studies have shown that nanoemulsions can improve the energy conversion efficiency and durability in electrochemical applications.²¹⁷

New Characterization Methods

It is also critical to innovate the characterization methods of nanoemulsions to better understand their properties. Currently, research on the characterization of nanoemulsions mainly focuses on the measurement of droplet size, size distribution, and zeta potential, which is very limited. Seeking new experimental techniques to evaluate all aspects of nanoemulsions can promote better understanding and broaden their applications and potential. Nanoparticle tracking analysis (NTA) uses a combination of laser scattering microscopy and CCD cameras to visualize and record the motion of nanoparticles in solution.²¹⁸ It can better identify and track individual particles undergoing Brownian motion to observe their movement state.²¹⁹ Small-angle X-ray scattering (SAXS) is an analytical technology that can detect relatively large, often nanoscale material structures through small-angle scattering signals. SAXS can be used to observe the size, shape, and morphology of nanoemulsions droplets and can dynamically follow their microscopic changes as they change with temperature. Compared with conventional transmission electron microscopy and scanning electron microscopy, SAXS requires less sample volume and is nondestructive.²²⁰ Raman spectroscopy is used to analyze scattering spectra with different frequencies from incident light, which allows for a more detailed observation of vibrational and rotational information at the molecular level. Through the analysis of sample characteristic peaks, the stability of nanoemulsions-encapsulated substances can be studied. Uzun et al conducted Raman spectroscopy analysis on lutein nanoemulsions, confirming the stability of lutein after emulsification and stabilization.²²¹ Veloso et al used surface-enhanced Raman spectroscopy to evaluate the photodynamic therapy of breast cancer cells in mice via a nanoemulsions loaded with a chloroaluminum phthalocyanine photosensitizer. They selected the Raman modes of proteins at 608 cm(−1) and lipids at 1231 cm(−1) to follow up on the survival rate of tumor cells, envisioning the rapid development of quantitative infrared thermal imaging.²²² In addition to the above methods, nuclear magnetic resonance,²²³ lipophilic fluorescent probes,²²⁴ and imaging techniques²²⁵ can be used as emerging characterization techniques to understand the stability, surface modification, release mechanism, and in vivo metabolism of nanoemulsions droplets. Introduction of more innovative nanoemulsions characterization experimental methods, examination of the characteristics behind nanoemulsions and optimization of formulations have great potential.

New Preparation Methods

At present, most methods for preparing nanoemulsions are high-energy emulsification methods, which require high energy consumption and high production equipment costs. In addition, low-energy emulsification methods require much energy during emulsification and a large amount of emulsifier, which poses certain challenges to the safety of nanoemulsions. Thus, it is necessary to find new preparation techniques. Recently, the process of emulsifying droplets via a metal organic framework (Mof) has gradually attracted the attention of researchers. Mofs are a new type of crystalline nanocomposite with a large surface area, surface adjustability, and high porosity.²²⁶ They also have a topological structure and can be used as an amphiphilic and surface-active material to emulsify droplets into emulsions. Studies have reported that Mof materials can better stabilize nanoemulsions, but the safety level requirements for nanoemulsions applied in the pharmaceutical or food industries are high, and some Mof materials prepared from metal or nonfood-grade organic linkers cannot meet safety requirements. To overcome this limitation, Chao et al used less toxic alkaline earth metals and an edible cyclodextrin-based Mof, which were stabilized by glycyrrhizic acid, and achieved good results,²²⁷ verifying the possibility of guiding the stability of edible-grade nanoemulsions. However, the preparation of nanocarriers based on Mof materials still requires long-term toxicity verification and the exploration of safer and more effective stabilizers. The preparation of safer and long-term stable nanoemulsions will broaden their potential applications as delivery systems in the fields of medicine and food.

Limitations

This study has certain limitations. First, some studies that do not use the same search strategy may be excluded from this study. Second, studies without author keywords were not included. Third, compared with newly published articles, older articles tend to receive more citations over time; therefore, the advantages of recent publications may not be apparent in this study.

Conclusions and Outlook

The present study used the bibliometric method and DDA software to study the literature published in SCIE and SSCI journals in the field of nanoemulsions research from 2013–2023. Both developed countries, represented by the USA, and developing countries, represented by China and India, have made important contributions to the field. With the pursuit of safer, more effective, environmentally friendly²²⁸ and more compliant nanoemulsions materials, the raw materials that meet different uses can be made into nanoemulsions forms to better meet researchers’ needs. In the fields of medicine, food, cosmetics and pesticide products, the superior antioxidant, slow-release and antibacterial properties of nanoemulsions can be better utilized to a greater extent. In the field of energy, nanoemulsions have the potential for energy savings and emissions reduction. However, to meet more application requirements and higher safety requirements, improvements and updates in nanoemulsions preparation technology and the treatment of waste nanoemulsions,²²⁹ as well as the possibility of new natural surfactants and droplet surface modifications, will increase the potential for the application of nanoemulsions and the development of green, natural, safe and high-performance multifunctional structural nanoemulsions. Further research is necessary in terms of reducing the preparation costs, improving preparation technology, conducting stability studies, and seeking better and safer surfactants. New characterization techniques for determining the characteristics of nanoemulsions, new preparation techniques mediated by Mof materials,^230–232 nanoemulsions carriers for delivering RNA,²³³ and artificial intelligence in the development and optimization of nanoemulsions technology^234–236 will become research hotspots in the future, further promoting the large-scale production and application of nanoemulsions. This study provides a novel perspective on the current research status of nanoemulsions and analyzes and summarizes current research hotspots. Hence, it can provide inspiration and useful information for researchers to expand their ideas and find more potential development directions.