Enhanced therapeutic efficacy of lipophilic amphotericin B against Candida albicans with amphiphilic poly(N-isopropylacrylamide) nanogels

Abstract

Candidiasis is a disease with skin rashes caused by the infectious fungus, Candida albicans, and can be potentially life-threatening, especially in immunodeficient patients. Amphotericin B (AmB) is a potent antifungal agent with a broad spectrum to treat Candidiasis, but its inherent low solubility and limited skin bioavailability have prevented its wider clinical use. In this study, we developed poly(N-isopropylacrylamide) (pNIPAM)-based nanogels as a versatile carrier to enhance AmB solubility and its efficacy. pNIPAM nanogels enhanced the solubility of AmB by 1.6-fold versus AmB alone. Accordingly, pNIPAM markedly improved the minimal fungicidal concentration (MFC) of AmB by 8 folds from 3.91 to 0.49 μg/mL. We also attached NH2 group to the pNIPAM nanogel to increase surface charges and investigated its effect on AmB antifungal activity. pNIPAM-NH2 has comparable activity in solid culture to pNIPAM, but 2-fold higher antifungal activity in liquid culture. Our pNIPAM and pNIPAM-NH2 nanogels may be useful as drug delivery agents for the treatment of local antifungal infections by AmB in solid and liquid environments, such as on skin and in blood, with high efficacy and sustainability.