Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphyloccocus aureus (MRSA) infections

Int J Pharm. 2018 Dec 20;553(1-2):109-119. doi: 10.1016/j.ijpharm.2018.10.024. Epub 2018 Oct 9.

Abstract

Antibiotic delivery via liposomal encapsulation represents a promising approach for the efficient topical treatment of skin infections. The present study aimed to investigate the potential of using different types of azithromycin (AZT)-loaded liposomes to locally treat skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains. Conventional liposomes (CLs), deformable liposomes (DLs), propylene glycol-containing liposomes (PGLs) and cationic liposomes (CATLs) encapsulating AZT were prepared, and their physical characteristics, drug release profiles, ex vivo skin penetration/deposition abilities, in vitro anti-MRSA activities (planktonic bacteria and biofilm) and cell biocompatibilities were assessed. The (phospho)lipid composition and presence of surfactant or propylene glycol affected the physical characteristics of the liposomes, the release profile of AZT, its deposition inside the skin, as well as in vitro antibacterial efficacy and tolerability with the skin cells. All the liposomes retained AZT inside the skin more efficiently than did the control and were biocompatible with keratinocytes and fibroblasts. CATLs, DLs and PGLs efficiently inhibited MRSA strain growth and were superior to free AZT in preventing biofilm formation, exhibiting minimal inhibitory concentrations and minimal biofilm inhibitory concentrations up to 32-fold lower than those of AZT solution, thus confirming their potential for improved topical treatment of MRSA-caused skin infections.

Keywords: Azithromycin; Biocompatibility; Biofilm; Cationic liposomes; Elastic liposomes; Methicillin-resistant Staphylococcus aureus (MRSA).

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Azithromycin / administration & dosage*
  • Azithromycin / pharmacokinetics
  • Azithromycin / pharmacology
  • Biofilms / drug effects
  • Cell Line
  • Chemistry, Pharmaceutical / methods
  • Drug Delivery Systems
  • Drug Liberation
  • Humans
  • Liposomes
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Propylene Glycol / chemistry
  • Skin Absorption
  • Skin Diseases, Bacterial / drug therapy
  • Skin Diseases, Bacterial / microbiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Swine

Substances

  • Anti-Bacterial Agents
  • Liposomes
  • Propylene Glycol
  • Azithromycin