Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid
{"title":"用于局部眼部给药的庆大霉素双体载体原位凝胶的开发:优化、体外表征、毒性和抗微生物评估。","authors":"Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid","doi":"10.34172/apb.2024.057","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The eye drops are the prominent preparation used to treat surface eye disease (bacterial conjunctivitis). However, they have some limitations i.e., short corneal residence, resulting in low ocular bioavailability and necessitating frequent dose administration. The present study developed gentamicin (GE) bilosomes (BM)- laden <i>in situ</i> gel to improve therapeutic activity. The <i>in situ</i> gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.</p><p><strong>Methods: </strong>The GE-BM was developed using the thin film hydration technique and optimized by D-optimal design. GE-BM was characterized for vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform electron microscope (FTIR). The optimized GE-BM (GE-BMopt) was incorporated into an <i>in situ</i> gel and assessed for physicochemical characteristics. GE-BMopt <i>in situ</i> gel was evaluated for <i>in vitro</i> release, <i>ex vivo</i> permeation, toxicity, and antimicrobial study.</p><p><strong>Results: </strong>GE-BMopt has a vesicle size of 185.1±4.8nm, PDI of 0.254, zeta potential of 27.6 mV, entrapment efficiency of 81.86±1.29 %, and spherical morphology. The FTIR study presented no chemical interactions between GE and excipients. GE-BMopt <i>in situ</i> gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and <i>ex-vivo</i> bio-adhesion. GE-BMopt-IG4 showed significant high and sustained release of GE (78.08±4.73% in 12h). GE-BMopt-IG4 displayed 3.27-fold higher <i>ex-vivo</i> goat corneal permeation than a pure GE solution. GE-BMopt-IG4 showed good corneal tolerance without any damage or irritation. GE-BMopt-IG4 showed significantly (<i>P</i><0.05) higher anti-bacterial activity (ZOI) against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> than pure GE solution.</p><p><strong>Conclusion: </strong>The study determined that the BM <i>in situ</i> gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530890/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of Gentamicin Bilosomes Laden <i>In Situ</i> Gel for Topical Ocular Delivery: Optimization, <i>In Vitro</i> Characterization, Toxicity, and Anti-microbial Evaluation.\",\"authors\":\"Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid\",\"doi\":\"10.34172/apb.2024.057\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The eye drops are the prominent preparation used to treat surface eye disease (bacterial conjunctivitis). However, they have some limitations i.e., short corneal residence, resulting in low ocular bioavailability and necessitating frequent dose administration. The present study developed gentamicin (GE) bilosomes (BM)- laden <i>in situ</i> gel to improve therapeutic activity. The <i>in situ</i> gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.</p><p><strong>Methods: </strong>The GE-BM was developed using the thin film hydration technique and optimized by D-optimal design. GE-BM was characterized for vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform electron microscope (FTIR). The optimized GE-BM (GE-BMopt) was incorporated into an <i>in situ</i> gel and assessed for physicochemical characteristics. GE-BMopt <i>in situ</i> gel was evaluated for <i>in vitro</i> release, <i>ex vivo</i> permeation, toxicity, and antimicrobial study.</p><p><strong>Results: </strong>GE-BMopt has a vesicle size of 185.1±4.8nm, PDI of 0.254, zeta potential of 27.6 mV, entrapment efficiency of 81.86±1.29 %, and spherical morphology. The FTIR study presented no chemical interactions between GE and excipients. GE-BMopt <i>in situ</i> gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and <i>ex-vivo</i> bio-adhesion. GE-BMopt-IG4 showed significant high and sustained release of GE (78.08±4.73% in 12h). GE-BMopt-IG4 displayed 3.27-fold higher <i>ex-vivo</i> goat corneal permeation than a pure GE solution. GE-BMopt-IG4 showed good corneal tolerance without any damage or irritation. GE-BMopt-IG4 showed significantly (<i>P</i><0.05) higher anti-bacterial activity (ZOI) against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> than pure GE solution.</p><p><strong>Conclusion: </strong>The study determined that the BM <i>in situ</i> gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.</p>\",\"PeriodicalId\":7256,\"journal\":{\"name\":\"Advanced pharmaceutical bulletin\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530890/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced pharmaceutical bulletin\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34172/apb.2024.057\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced pharmaceutical bulletin","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34172/apb.2024.057","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Development of Gentamicin Bilosomes Laden In Situ Gel for Topical Ocular Delivery: Optimization, In Vitro Characterization, Toxicity, and Anti-microbial Evaluation.
Purpose: The eye drops are the prominent preparation used to treat surface eye disease (bacterial conjunctivitis). However, they have some limitations i.e., short corneal residence, resulting in low ocular bioavailability and necessitating frequent dose administration. The present study developed gentamicin (GE) bilosomes (BM)- laden in situ gel to improve therapeutic activity. The in situ gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.
Methods: The GE-BM was developed using the thin film hydration technique and optimized by D-optimal design. GE-BM was characterized for vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform electron microscope (FTIR). The optimized GE-BM (GE-BMopt) was incorporated into an in situ gel and assessed for physicochemical characteristics. GE-BMopt in situ gel was evaluated for in vitro release, ex vivo permeation, toxicity, and antimicrobial study.
Results: GE-BMopt has a vesicle size of 185.1±4.8nm, PDI of 0.254, zeta potential of 27.6 mV, entrapment efficiency of 81.86±1.29 %, and spherical morphology. The FTIR study presented no chemical interactions between GE and excipients. GE-BMopt in situ gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and ex-vivo bio-adhesion. GE-BMopt-IG4 showed significant high and sustained release of GE (78.08±4.73% in 12h). GE-BMopt-IG4 displayed 3.27-fold higher ex-vivo goat corneal permeation than a pure GE solution. GE-BMopt-IG4 showed good corneal tolerance without any damage or irritation. GE-BMopt-IG4 showed significantly (P<0.05) higher anti-bacterial activity (ZOI) against Staphylococcus aureus and Escherichia coli than pure GE solution.
Conclusion: The study determined that the BM in situ gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.