Pluronic F-127 Hydrogel for Delivering Antimicrobial Agents: a Bibliometric Analysis using Scopus Database

Infectious diseases caused by pathogenic microorganisms pose significant threats to public health globally. The emergence of antibiotic-resistant bacteria has further complicated the treatment of these infections, necessitating the exploration of alternative therapeutic strategies. Among these strategies, the use of hydrogels as delivery systems for delivering antimicrobial agents has gained considerable attention. This paper presents a comprehensive bibliometric analysis of the utilization of Pluronic F-127 (PF-127) hydrogel for delivering antimicrobial agents. The aim of this study is to explore the current research landscape, identify key trends, influential authors, and prominent journals in this field. The analysis is based on a systematic search conducted using the Scopus database. The analysis covered publication trends, geographic distribution, influential authors, and key journals in the field of PF-127 hydrogel-based antimicrobial agent delivery. The results revealed the growing interest in this field, with a focus on countries such as India, the United States, and Egypt. The analysis also identified top authors, institutions, and journals contributing to the research. The findings reveal the growth of research in this area, highlighting the potential of PF-127 hydrogel as a promising vehicle for antimicrobial agent delivery. It highlights the need for further research to optimize formulation parameters, explore combination therapies, conduct in vivo studies, and promote collaboration to maximize the therapeutic potential of PF-127 hydrogel-based delivery systems in combating infectious diseases and antimicrobial resistance. This paper provides valuable insights into the existing literature and serves as a reference for future research and development in the field.


INTRODUCTION
Infectious diseases caused by pathogenic microorganisms pose significant threats to public health globally. The use of antimicrobial agents is essential in addressing the challenges posed by infectious diseases and antimicrobial resistance. 1 However, the effectiveness of these agents is often limited by factors such as poor bioavailability, rapid clearance, and the emergence of resistant strains. The emergence of antibiotic-resistant bacteria has further complicated the treatment of these infections, necessitating the exploration of alternative therapeutic strategies. Among these strategies, the use of hydrogels as delivery systems for antimicrobial agents has gained considerable attention. 2 Hydrogels offer a three-dimensional (3D) network capable of encapsulating and releasing drugs in a controlled and sustained manner.2 Pluronic F-127 (PF-127) hydrogel, in particular, has emerged as a promising candidate due to its unique properties and potential to combat microbial infections. 3 PF-127 hydrogel has emerged as a promising vehicle for delivering antimicrobial agents in various biomedical applications. It is a block copolymer composed of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) segments. 4 This amphiphilic nature of PF-127 enables it to self-assemble into micelles at low temperatures and undergo sol-gel transition at physiological temperatures. 5 This transition behavior has been extensively exploited in drug delivery applications, as it allows for convenient gelation at room temperature, facilitating ease of administration. The unique properties of PF-127, including its thermosensitivity, biocompatibility, and ability to sol-gel transition, make it an attractive choice for controlled and sustained release of antimicrobial agents. 6,7 This hydrogel system offers several advantages, such as localized drug delivery, prolonged drug release, and the ability to create an optimal environment for wound healing while combating infections. 8 PF-127 hydrogel lacks intrinsic antimicrobial activity against Staphylococcus aureus and Escherichia coli, but its antiadhesive properties and biocompatibility make it a promising neutral carrier system for antibiotics and antimicrobial compounds in biomedical applications. 7 Its antiadhesive properties indirectly contribute to preventing microbial infections by inhibiting bacterial adhesion. PF-127 hydrogel reduces the likelihood of bacterial colonization and subsequent infection. 9 PF-127 hydrogel provides a promising solution by encapsulating and releasing antimicrobial agents in a controlled manner, thereby maximizing their therapeutic potential. 4 Understanding the interplay between the hydrogel and the loaded agents is crucial for optimizing the therapeutic efficacy and ensuring controlled release profiles. 10 A deeper understanding of the release mechanisms will aid in the design and development of hydrogel-based delivery systems with tailored release profiles for specific. 11 This paper aims to provide a comprehensive overview of the current state of research on PF-127 hydrogel for delivering antimicrobial agents. It encompasses a bibliometric analysis using the Scopus database to explore publication trends, geographic distribution, influential authors, and key journals in this field. Understanding the literature landscape and the advancements made in PF-127 hydrogel-based antimicrobial agent delivery will enable researchers to identify knowledge gaps, potential areas for further investigation, and emerging trends in the field. Moreover, this analysis will facilitate collaboration and knowledge sharing among researchers, leading to accelerated advancements and the development of more effective strategies for antimicrobial agent delivery. The present study explores the current research landscape, identify key trends, influential authors, and prominent journals associated with evaluatinng the potential of PF-127 as a carrier of antimicrobial agents.

Search strategy and data collection
The literature search was performed on May 23, 2023, using the Scopus database. The search strategy aimed to collect data on journal articles published until 2022 while excluding certain publication types such as reviews, editorials, conference papers, book chapters, books, letters, notes, short surveys, erratum, reports, and retracted papers. Only articles published in English were considered, excluding publications in other languages. The following search query was employed: TITLE-ABS-KEY ( ( poloxamer 407 OR "Pluronic F-127" OR pf-127 OR pluronic-f-127 OR "Pluronic™ F-127" OR "Plutonic F127" OR pf127 OR "Pluronic® F-127" OR "Pluronic® F127" ) AND ( antibiotic* OR antimicrobial* OR antifungal* OR antiviral* OR anti-biofilm ) ) AND ( LIMIT-TO ( DOCTYPE, "ar" ) ) AND ( LIMIT-TO ( LANGUAGE, "English" ) ) AND ( LIMIT-TO ( SRCTYPE, "j" ) ) AND ( EXCLUDE ( PUBYEAR, 2023 ) ) By employing the above search strategy, a focused and comprehensive dataset of journal articles related to Pluronic F-127 hydrogel for delivering antimicrobial agents was obtained, adhering to the specified criteria for publication type, language, and publication year. This search query focuses on articles that mention the specific term "Pluronic F-127" and its modifications in conjunction with different keywords corresponding to different antimicrobial agents. The use of the operator "OR" broadens the search to include different variants of PF-127 and antimicrobial agents.

Analysis of variables and visualization
The metadata was analyzed using R Studio and the bibliometrix package, which is a powerful open-source tool specifically designed for conducting comprehensive science mapping analysis within the R statistical programming language. 12 The extracted data was further analyzed and interpretation was done under the following titles: overview of publication trends, geographic distribution of research, most cited articles, analysis of keywords, identification of top authors and institutes, identification of influential journals, and evaluation of collaboration networks. In addition, the data was visualized using network visualization software VOSviewer (version 1.6.17). 13

RESULTS AND DISCUSSION
Scopus offers a vast collection of scholarly literature, including journals, conference papers, patents, and book series, from various disciplines. It covers a wide range of subject areas, making it suitable for multidisciplinary research. 14 Web of Science might have limited coverage of literature, particularly in some emerging or specialized fields. However, this can be due to the fact that Web of Science maintains strict inclusion criteria, ensuring the quality and reliability of the indexed publications. 15 This database is renowned for its rigorous selection process, which minimizes the risk of including low-quality or predatory journals in the analysis. 14,15 It is important to note that both Scopus and Web of Science have their strengths and weaknesses when it comes to bibliometric analysis. Researchers should consider their specific research needs, disciplinary focus, and intended analysis goals while selecting the most appropriate database for their bibliometric studies.

Overview of Publication Trends
This paper provides a comprehensive overview of research on PF-127 hydrogel for delivering antimicrobial agents, covering a period from 1981 to 2022 (Table 1). The analysis is based on 161 sources (journals) resulting in a total of 325 documents. The field has shown an annual growth rate of 10.01%. The average age of the documents is 6.31 years, while the average number of citations per document is 23.02. The collected data includes a total of 13,643 references. The document contents consist of 3,354 keywords Plus  (7), Dentistry (7) to name a few. Line diagram illustrating the publication trend of articles in Pluronic F-127 hydrogel research for delivering antimicrobial agents from 1981 to 2022 is inserted as Figure 2. In addition, the line diagram illustrating the mean total citations per year (MeanTCperYear) is inserted as Figure 2.

Geographic Distribution of Research
Scientific production on the use of Pluronic F-127 hydrogel for delivering antimicrobial agents varies across different countries (Figure 3). India has the highest number of articles with 112 publications, followed closely by the United States with 107 articles. Egypt has contributed 85 articles, while Brazil and China have 83 and 82 articles, respectively. Spain has published 51 articles, Turkey 49, and Thailand 42. France and the United Kingdom have comparatively lower numbers of publications, with 33 and 31 articles, respectively, on this topic. The map representing Country Scientific Production (worldwide data) is inserted as Figure 3a. The map illustrating the country collaboration analysis is inserted as Figure  3b. The USA was found to be the country with the broadest collaboration network which includes active scientific relationships with 16 other countries. This was followed by India and United Kingdom as second and third active scientific collaborations (8 and 7 countries).

Most Cited Articles
The characteristics of the top ten most cited papers in Pluronic F-127 hydrogel research for delivering antimicrobial agents are given in Table 2. Among the 10 papers, three highly cited papers were published in the International Journal of Pharmaceutics, Two each in AAPS PharmSciTech journal and Journal of Controlled Release. In

Analysis of Keywords
The Multiple Correspondence Analysis (MCA) was employed to analyze the keywords in our dataset. It condenses vast data with multiple variables into a reduced-dimensional space, creating a visually informative two-dimensional (or three-dimensional) graph. The graph utilizes the distance between points on the plane to represent the similarity between keywords. Keywords that approach the center point indicate a higher level of attention in recent. The interpretation of the results is based on the positions of the points and their distribution along the dimensions. The closer words are represented on the map, the more similar their distribution is years. 26 The conceptual structure analysis of the top 50 keywords Plus, author keywords, and keywords in titles is given in Figure 4. The top 50 keywords Plus were divided into five clusters: Cluster 1 (anti-bacterial agents, anti-infective agent), Cluster 2 (human, drug effect, humans, chemistry), Cluster 3 (drug carriers, animal, male, female, gels, hydrogel, unclassified drug, priority journal, drug carrier, animals), Cluster 4 (animal tissue, animal model, animal experiment, in vivo study), and the remaining were clubbed as Cluster 5. Similarly, the top 50 author keywords and keywords in titles were clustered into five groups as given in Figure 5 and 6.

Identification of Top Authors and Institutes
Bar diagram illustrating the top productive authors publishing articles in Pluronic F-127 hydrogel research for delivering antimicrobial agents is inserted as Figure 8. According to Lotka's law, 1494 authors (89.03%) among the total 1678 identified are considered occassional authors whereas 48 authors were identified as the core authors (who published ≥3 articles in the present case). Lotka's law characterizes the distribution of authorship in a specific field, stating that the frequency of authors publishing a certain number of articles follows an approximate inverse-square relationship. According to Lotka's law, the ratio of authors who publish a specific number of articles to the number of authors who publish only one article remains relatively constant. Additionally, Lotka's law confirms that as the number of Figure 10 The network visualization map indicating the connections between authors and countries. Specifically, authors with a minimum of three documents (a) and countries with a minimum of three documents (b) were selected for inclusion in the map. The size of each circle/frame in the map represents the total number of published articles, with larger circles indicating a higher publication count. On the other hand, the width of the lines in the map signifies the strength of the links, with wider lines indicating stronger connections. The distance between two circles in the map reflects the degree of relatedness between the corresponding nodes