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<p>Topical mupirocin (MP) remains clinically important for managing skin infections, yet its therapeutic efficacy is constrained by poor dermal permeation and the rapid emergence of bacterial resistance. To address these limitations, we developed and systematically evaluated a novel liposome-in-hydrogel nanofilm composed of mupirocin-loaded liposomes embedded in a crosslinked poly(vinyl alcohol)/poly(ethylene glycol) polymeric matrix. MD simulations revealed that mupirocin incorporation did not destabilize the lipid bilayer, while preferential interactions with POPE lipids over DPPC were observed. Liposomes prepared via thin-film hydration exhibited nanoscale dimensions (SEM ~ 147 nm; DLS ~ 249 nm), a stable negative surface charge (− 46 mV), high encapsulation efficiency (99%), and substantial drug loading (33%). Embedding these vesicles into the hydrogel matrix yielded a mechanically stable nanofilm, with SEM and FTIR confirming homogeneous liposome integration and reduced pore size relative to the unloaded control. The formulation prolonged drug release, extending 70% cumulative release to ~ 24 h versus ~ 4 h in drug-only hydrogel. <i>Ex-vivo</i> permeation studies across murine skin demonstrated ~ 50% higher cumulative delivery compared with unreinforced films. Mechanical testing indicated increased tensile strength and stiffness, supporting its potential as a durable topical dressing. Biological assays confirmed preserved antimicrobial activity against methicillin-resistant <i>Staphylococcus aureus</i> with inhibition zones (~ 34–35 mm) equivalent to commercial mupirocin discs, alongside high fibroblast viability (89–92%) evidencing cytocompatibility. In summary, this study demonstrates that the liposome-in-hydrogel nanofilm is a promising biocompatible carrier that sustains mupirocin release, enhances dermal penetration, and maintains antimicrobial efficacy.</p>

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Molecular dynamics and preparation of a liposome-loaded polymeric nanofilm to enhance the transdermal permeation of mupirocin

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Ghazal Nowroozi,
  • Zahra Asvar,
  • Maryam Chalabi,
  • Mohsen Shahlaei,
  • Leila Hosseinzadeh,
  • Sajad Moradi,
  • Elham Arkan

摘要

Topical mupirocin (MP) remains clinically important for managing skin infections, yet its therapeutic efficacy is constrained by poor dermal permeation and the rapid emergence of bacterial resistance. To address these limitations, we developed and systematically evaluated a novel liposome-in-hydrogel nanofilm composed of mupirocin-loaded liposomes embedded in a crosslinked poly(vinyl alcohol)/poly(ethylene glycol) polymeric matrix. MD simulations revealed that mupirocin incorporation did not destabilize the lipid bilayer, while preferential interactions with POPE lipids over DPPC were observed. Liposomes prepared via thin-film hydration exhibited nanoscale dimensions (SEM ~ 147 nm; DLS ~ 249 nm), a stable negative surface charge (− 46 mV), high encapsulation efficiency (99%), and substantial drug loading (33%). Embedding these vesicles into the hydrogel matrix yielded a mechanically stable nanofilm, with SEM and FTIR confirming homogeneous liposome integration and reduced pore size relative to the unloaded control. The formulation prolonged drug release, extending 70% cumulative release to ~ 24 h versus ~ 4 h in drug-only hydrogel. Ex-vivo permeation studies across murine skin demonstrated ~ 50% higher cumulative delivery compared with unreinforced films. Mechanical testing indicated increased tensile strength and stiffness, supporting its potential as a durable topical dressing. Biological assays confirmed preserved antimicrobial activity against methicillin-resistant Staphylococcus aureus with inhibition zones (~ 34–35 mm) equivalent to commercial mupirocin discs, alongside high fibroblast viability (89–92%) evidencing cytocompatibility. In summary, this study demonstrates that the liposome-in-hydrogel nanofilm is a promising biocompatible carrier that sustains mupirocin release, enhances dermal penetration, and maintains antimicrobial efficacy.