ascorbic-acid and Soft-Tissue-Infections

Staphylococcus aureus infections affecting the skin and soft tissues are of significant health concern and an unmet need to be addressed. The lack of drug penetration into the infectious site is the main clinical challenge. Once the pathogen invades the wounded skin, it attenuates biological response pathways, leading to chronic infection. Wound infections are associated with alkaline pH due to the presence of bacteria, whereas creation of an acidic environment around the wound bed promotes faster healing. Herein, we develop injectable drug loaded nanoparticulate system of vancomycin encapsulated polycaprolactone nanoparticles coated with polyelectrolyte-Vitamin C in polyvinyl alcohol-alginate gel (D-PCL-PVc-PVA(Alg). The nanoparticles were synthesized via emulsion solvent evaporation method with polyallylamine hydrochloride-vitamin C coating, had a size of ∼35.93±3.00nm and improved stability of -34.5±6mV. PVA-Alginate gel served as a carrier, wherein the nanoparticles created an acidic environment pH (5-6), exhibiting a strong anti-staphylococcal activity (fivefold) when compared with the widely used antibiotic vancomycin. Ex-vivo permeation studies and imaging revealed that D-PCL-PVc-PVA(Alg), when injected, goes deep to the infectious crevices, destroying S.aureus completely with sustained drug release through diffusion with utmost biocompatibility towards L929 cells. This work substantiates use of D-PCL-PVc-PVA(Alg) for skin and soft tissue infections (SSTI).

Topics: Alginates; Animals; Anti-Bacterial Agents; Ascorbic Acid; Cell Line; Drug Compounding; Drug Liberation; Fibroblasts; Glucuronic Acid; Hexuronic Acids; Hydrogen-Ion Concentration; Mice; Nanoparticles; Permeability; Polyesters; Polyvinyl Alcohol; Skin; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Swine; Tissue Culture Techniques; Vancomycin