{"title":"质量源于设计辅助开发用于治疗白色念珠菌感染的卢利康唑经溶胶体。","authors":"Gurmeet Singh, Raj Kumar Narang","doi":"10.1089/adt.2023.059","DOIUrl":null,"url":null,"abstract":"<p><p>The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of <i>Candida albicans</i> infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and <i>in vitro</i> study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm<sup>3</sup>. The <i>in vitro</i> results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. <i>In vivo</i>, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1-17"},"PeriodicalIF":1.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quality by Design Assisted Development of Luliconazole Transethosomes in Gel for the Management of <i>Candida albicans</i> Infection.\",\"authors\":\"Gurmeet Singh, Raj Kumar Narang\",\"doi\":\"10.1089/adt.2023.059\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of <i>Candida albicans</i> infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and <i>in vitro</i> study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm<sup>3</sup>. The <i>in vitro</i> results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. <i>In vivo</i>, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.</p>\",\"PeriodicalId\":8586,\"journal\":{\"name\":\"Assay and drug development technologies\",\"volume\":\" \",\"pages\":\"1-17\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Assay and drug development technologies\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/adt.2023.059\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Assay and drug development technologies","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/adt.2023.059","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/29 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Quality by Design Assisted Development of Luliconazole Transethosomes in Gel for the Management of Candida albicans Infection.
The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of Candida albicans infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and in vitro study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm3. The in vitro results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. In vivo, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.
期刊介绍:
ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application.
ASSAY and Drug Development Technologies coverage includes:
-Assay design, target development, and high-throughput technologies-
Hit to Lead optimization and medicinal chemistry through preclinical candidate selection-
Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis-
Approaches to assays configured for gene families, inherited, and infectious diseases-
Assays and strategies for adapting model organisms to drug discovery-
The use of stem cells as models of disease-
Translation of phenotypic outputs to target identification-
Exploration and mechanistic studies of the technical basis for assay and screening artifacts