Novel liposomal forms of antifungal antibiotics modified by amphiphilic polymers

Abstract

A method has been developed, for incorporating macrocyclic polyene antibiotics nistatin and amphotericin B into liposomes containing phosphatidylcholine and cholesterol (7:3) or phosphatidylcholine, cholesterol, and cardiolipin (7:3:1), the membranes of which were modified with an amphiphilic polymer of N-vinylpyrrolidone, carrying one terminal n-octadecyl group and having a molecular weight of 4000 Da. The amount of antibiotics within such liposomal nanocarriers may be as high as 17-22%. It was demonstrated that the modified liposomes have sizes in the range 150-200 nm and exhibit increased long-term storage stability and increased resistance to disrupting agents (Triton X-100 or ethanol) and ultrasound. The antifungal activity of the liposomal preparations obtained exceeded that of the antibiotics not subjected to immobilization.