In-Vitro and In-Vivo Studies on Novel Chitosan-g-Pluronic F-127 Copolymer Based Nanocarrier of Amphotericin B for Improved Antifungal Activity

The present communication is focusing on development of safe nanotemplates for sustained delivery of amphotericin B (AmB). We synthesized a block copolymer based on chitosan and Pluronic F-127 (PEO-b-PPO-b-PEO). Selection of Pluronic F-127 was based upon the criteria's that it has smaller size, higher aqueous solubility and stability whereas; chitosan is a non toxic, biodegradable polysaccharide. AmB loaded micelles were prepared by direct dissolution and pH dependent method. Various formulations were prepared using different drug polymer ratio to optimize the size, size distribution, zeta potential and drug loading efficiency. Optimized formulation was characterized for drug release pattern, haemolytic potential, in-vitro anti fungal activity and, in-vivo toxicity and compared with the marketed formulation (fungizone). The particle size and zeta potential of the micelles were found in the range between 90.2 +/- 10.21 to 148.7 +/- 21.03 and -16.3 +/- 4.24 to +31.1 +/- 6.10, respectively. The drug loading was found between 16.7 +/- 4.76% to 33.3 +/- 2.67% for all the developed formulations. Developed formulations showed negligible hemolytic toxicity with comparison to marketed formulation. In vitro antifungal studies demonstrated that micelles were more active than fungizone against C. albicans and A. fumigatus. Furthermore, AmB showed less nephrotoxicity when encapsulated in micelles in comparison to marketed formulation. These results together revealed that the developed formulation would be a safe and efficacious alternative to current marketed formulation to ameliorate the treatment of fungal infection.