A mucoadhesive nanolipo gel containing Aegle marmelos gum to enhance transdermal effectiveness of linezolid for vaginal infection: In vitro evaluation, in vitro-ex vivo correlation, pharmacokinetic studies

Bhabani Sankar Satapathy, Biswabhusan Biswal,Snigdha Pattnaik,Reena Parida,Rudra Narayan Sahoo

INTERNATIONAL JOURNAL OF PHARMACEUTICS(2023)

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摘要
Effective treatment of vaginal infections with conventional antibiotics often faces challenges like unavoidable dose-related side effects with increased risk of bacterial resistance. The study aims to deliver linezolid through natural gum based mucoadhesive nano lipogel to improve therapeutic effectiveness against vaginal infections. The linezolid loaded nanoliposomes (LNLs) were developed by thin film hydration method and were charac-terized by FTIR, DSC, XRD, FESEM, particle size analysis, zeta potential, drug loading capacity, in vitro release study etc. Selected LNLs was loaded into suitable gel formulation containing Aegle marmelos gum (as the mucoadhesive agent) and evaluated for in vitro, in vivo potentiality. FTIR/DSC test confirmed absence of any major interaction between selected drug and excipients. XRD showed amorphization of the drug encapsulated in NLs. FESEM studies showed spherical LNLs having smooth surface. LNLs had nanosize (51.03 nm), negative surface charge (-25.7 mV), satisfied drug loading capacity (11.5 +/- 0.7 %) with sustained drug release. The experimental LNLs loaded lipogel showed desired physico-chemical properties viz. viscosity (37000 cps), spreadability (6.5 gm.cm sec-1), mucoadhesion (21.9 gf) and 61.04 % release of drug across rabbit vaginal mucosal membrane. The nanolipo gel exhibited improved antimicrobial activity against E. coli and C. albicans with respect to the pure linezolid. A good correlation was observed in between in vitro drug release and ex vivo permeation. Improved pharmacokinetic parameters like AUC, AUMC, MRT, Vd was observed for experimental nanolipo gel Vs. marketed formulation. The experimental nanolipo gel could be explored further for futuristic clinical application.
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关键词
Linezolid,Nanolipo gel,Mucoadhesion,Aegle marmelos gum,Antimicrobial effectiveness,Pharmacokinetics
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