Saturated Fatty Acid-Based In Situ Forming Matricesfor Localized Antimicrobial Delivery

Abstract

In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistantStaphylococcus aureus(MRSA) is a significant problem in various treatments and control of infections.Biocompatible materials with saturated fatty acids of different chain lengths (C8–C18) were studied asmatrix formers of localized injectable vancomycin HCl (VCM)-loaded antisolvent-induced in situforming matrices. The series of fatty acid-based in situ forming matrices showed a low viscosity(5.47–13.97 cPs) and pH value in the range of 5.16–6.78, with high injectability through a 27-Gneedle (1.55–3.12 N). The preparations exhibited low tolerance to high concentrations of KH2PO4solution (1.88–5.42%v/v) and depicted an electrical potential change during phase transformation.Their phase transition and matrix formation at the microscopic and macroscopic levels dependedon the chain length of fatty acids and solvent characteristics. The VCM release pattern dependedon the nucleation/crystallization and solvent exchange behaviors of the delivery system. The 35%w/vof C12–C16fatty acid-based in situ forming matrix prolonged the VCM release over seven daysin which C12, C14, C16–based formulation reached 56, 84, and 85% cumulative drug release at 7thday. The release data fitted well with Higuchi’s model. The developed formulations presentedefficient antimicrobial activities against standardS. aureus, MRSA,Escherichia coli, andCandida albicans.Hence, VCM-loaded antisolvent-induced fatty acid-based in situ forming matrix is a potential localdelivery system for the treatment of local Gram-positive infection sites, such as joints, eyes, dermis ofsurgery sites, etc., in the future.