DEVELOPMENT AND IN VITRO-IN VIVO EVALUATION OF LINEZOLID-LOADED NIOSOMAL TOPICAL GEL FOR PRECISION THERAPY OF GRADE I DIABETIC FOOT ULCERS

Abstract

Background: Grade I diabetic foot ulcers are clinically relevant early ulceration where the lesion is superficial. However, microbial colonisation, impaired perfusion, neuropathy and dysregulated inflammation will accelerate the progression if not properly taken care of. Linezolid is an oxazolidinone antibiotic agent that is synthetic and able to act against Gram-positive pathogens. The Gram-positive pathogens comprise methicillin-resistant Staphylococcus aureus and enterococci. However, systemic therapy is not justified in the case of uninfected ulcers. Along with that, it may also increase avoidable exposure. The objective of our study was to formulate and evaluate a topical gel containing linezolid-loaded niosomes for localized antibacterial action and supportive wound healing in the management of early-stage diabetic foot ulcer. Linezolid-loaded niosomes were prepared by thin-film hydration using Span/Tween surfactants and cholesterol. A Box-Behnken design teaching on surfactant concentration, cholesterol concentration and sonication time on vesicle size, polydispersity index, zeta potential, entrapment efficiency and 24 h drug release. Optimized dispersion incorporated into Carbopol 934/HPMC gel was characterized for physicochemical, rheological, release, skin-retention and antimicrobial activity and diabetic wound healing performance. According to the findings, the modified niosomes demonstrated a particle size of 148.6 nm, PDI of 0.214, zeta potential of -31.7 mV, and entrapment efficiency of 83.6%. The niosomal gel features a pH that is compatible with the skin, uniform drug content, pseudoplastic viscosity, and control release over a period of 24 hours, the ex vivo skin retention of it was greater than the plain linezolid gel. Sustained activity against Gram-positive wound pathogens was indicated by antimicrobial assays. In excision wounds of diabetic rats, the contractile action of the niosomal gel increased the collagen deposition and reduced the time of epithelialization compared to the untreated and plain gel groups. This was statistically significant with p value < 0.05. The study concludes that the Linezolid (LNZ) loaded niosomal gel can potentially provide a rational localized treatment platform for Grade I diabetic foot ulcer. Nonetheless, clinical translation will take place upon validation of human safety, selection based on infection status and a controlled clinical evaluation of the formulation.