Vesicular phospholipid gels: A new strategy to improve topical antimicrobial dermatotherapy

Abstract

Therapeutically effective and biocompatible dermal formulations that can ensure localization of a high level of antimicrobial drug at the site of action for an appropriate duration, while at the same time providing intrinsic reepithelization properties, are of particular importance for the treatment of infected and injured skin. The current research aimed to explore the potentials of using vesicular phospholipid gels (VPGs), semisolid formulations consisting of tightly packed liposomes (100–––200 nm), as innovative local depot drug vehicles for advanced topical dermatotherapy. Ciprofloxacin hydrocholoride (CPX) was selected as a model hydrophilic antibacterial drug and was loaded into several VPGs, differing in their composition. Various CPX-loaded VPGs (CPX-VPGs) were evaluated in vitro for the rheological and physicochemical characteristics, drug release profile, stability under in vivo mimicked conditions and during storage, skin permeability, biocompatibility with the epidermal cells, antibacterial efficacy and wound healing assay, to determine the optimal CPX-VPG for topical dermatotherapy. Viscosity and bilayers fluidity of VPGs affected the release of CPX from CPX-VPGs and its skin localization, limiting CPX percutaneous absorption. All CPX-VPGs exhibited even a 2-fold increase in anti-biofilm activity against both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolate compared to the free drug, while showing no toxic effects on human keratinocytes in vitro. Based on the pronounced proliferative effects on keratinocytes, superior in vitro wound healing effect and drug localization on/inside the skin, CPX-VPGs containing chitosan and hydrogenated phospholipid proved to be the most promising for topical dermatotherapy. These findings, along with increased bioadhesiveness and the slow drug release, with CPX concentrations significantly above the minimum biofilm inhibitory concentrations for bacteria typical in infected wounds, would contribute not only to the improvement of the antimicrobial dermatotherapy, but also to reduction of the frequency of the drug administration.