Development of lipid nanoparticles with nystatin for an antifungal action

Abstract

Fungal diseases currently affect about a quarter of the population worldwide. Fungi infections caused by Candida albicans have been described as a significant concern to public health. The spectrum of clinical diseases caused by this fungi species range between vulvovaginal candidiasis, oral candidiasis, candidemia and mucositis. The emergence of resistance mechanisms towards antifungal therapy greatly hampers successful management of illness and patient outcome. Nystatin, an antifungal drug, is categorized as a class IV of Biopharmaceutical Classification System, presenting low aqueous solubility and low intestinal permeability. Nowadays, the emerging platform of nanotechnology and lipid nanoparticles, notably solid lipid nanoparticles (SLN), has been subject to growing attention over recent past, owing to the promising properties of vectorization among a substantial variety of pharmaceutical drugs. Due to its hydrophobic proprieties, nystatin was encapsulated in SLN. Thus aiming to understand the relationship between the use of nanosystems and the improvement of the therapeutic effect. The aim of this work was to formulate SLN with nystatin by different methods (high speed homogenization and ultrasonication) with optimization of several parameters and formulation of 2 gels (one of them containing nanoparticles).
 Initially, 3 lipids were used: Compritol® 888 ATO, cetyl palmitate and Precirol® ATO 5 and, after the study of several parameters (size, encapsulation efficiency (EE) and polymorphic behaviour of the lipids), Precirol® ATO 5 was chosen as the lipid with the most satisfactory results. The results of the present work showed that the assay method of nystatin was linear, specific and presented repeatability. The average diameter of empty nanoparticles (NPs) and with drug (Precirol-NYS NPs) was, respectively, 306 nm and 260 nm and an EE of 67.8%. Regarding stability, SLN with drug proved to be more stable than SLN without drug. The polymer used for formulation of gels was the polymer commonly known by the trade name Carbopol® 940. The yield of 0.5% Carbopol® gel preparations and 0.5% Carbopol® gel + 10% Precirol-NYS NPs were 87.2% and 91.39%, respectively.