Advanced Drug Delivery System for New Chemical Entity Destined for Wound Therapy: Anti-biofilm Potential of Novel Drug Delivery System

Abstract

Damage to the healthy skin barrier leads to a rapid and complex process of wound healing to restore the skins normal function and structure. The presence of bacteria in wounds such as pressure ulcers and diabetic foot ulcers impairs the healing process and leads to increased patient morbidity and mortality as well as reduced patient life quality. Bacteria growing in the wound environment form biofilm, a thick hydrophobic matrix that provides an optimal environment for bacterial survival. In recent years, an increase of bacterial resistance against antibiotics existing on the market today has led to the development of new treatment options such as e.g. antimicrobial photodynamic therapy (PDT). Lecithin/chitosan nanoparticles containing a New Chemical Entity (NCE) were prepared and characterized for their size distribution and zeta potential. Entrapment of NCE in nanoparticles was approximately 23 %. The nanoparticles exhibited a bimodal size distribution with a representative size of around 250 nm. The overall surface charge was found to be slightly positive. A method for evaluating elimination Staphylococcus epidermidis biofilm after the treatment with NCE-mediated PDT was optimized throughout this project. During biofilm elimination, NCE in both free form and entrapped in nanoparticles were applied to the biofilm prior to the light irradiation. NCE concentrations of 0.01, 0.1 and 1 mM were found to be safe for use, a light dose of both 37 and 90 J/cm2 were found to be applicable, and treatment intervals of 6 and 24 hours with NCE prior to light irradiation were used. The effect of NCE on biofilm without light exposure was also evaluated. Vancomycin was used as a standard positive control during the entire experimental period. The results indicated a very small reduction of intact biofilm after the treatment with NCE-mediated PDT under optimal growth conditions for S. epidermidis. Moreover, biofilm reduction was also observed after treatment with NCE alone. Although the results exhibited minimal biofilm reduction after PDT treatment, this study indicate that NCE-mediated PDT has the potential to be a new optional treatment against biofilm-forming bacteria that colonizes chronic wounds. Further optimization of the elimination method is necessary, and highly interesting.