Enhancing the performance of PEG-b-PCL copolymers as precursors of micellar vehicles for amphotericin B through its conjugation with cholesterol

Amphotericin B (AmB) is an antifungal drug with a broad spectrum of action. It has few resistance reports, and it is widely used for treating invasive fungal infections. However, it has many drawbacks related to its administration and undesired side effects, such as nephrotoxicity. The use of polymer micelles not only increases the solubility of AmB in aqueous media, but also attenuates its toxicity. Nevertheless, polymer micelles have low loading capacities because they interact weakly with AmB, which is an amphiphilic and amphoteric molecule. In the present research, we investigate the effect of conjugating mPEG-b-PCL with cholesterol. This is a biocompatible and biodegradable block copolymer commonly used as a drug carrier. The results indicated that the presence of cholesterol increased the encapsulation efficiency and loading capacity of AmB, and improves their ability to impart controlled release. Compared with Fungizone (R) as reference, AmB-loaded polymer micelles presented lower in vitro efficacy against Candida albicans SC5314, and this was seen as an increase in minimum inhibitory concentration. However, in vivo assessment of antifungal activity using an invertebrate Galleria mellonella model for invasive candidiasis showed comparable efficacy. The toxicity of AmB against red blood cells was attenuated upon encapsulation. The results indicated that in addition to the favourable interaction of AmB-micelle core from the presence of cholesterol, a synergistic effect was found with the segment of PCL, thereby resulting in improved performance.