IN VITRO STUDY ABOUT ACTIVITY/TOXICITY PROFILES OF CONTROLLED HEATING TREATMENT AMPHOTERICIN B IN MICELLAR SYSTEM
Amphotericin B; superaggregates; pharmaceutical technology
The aims of this work were compared the absorption spectrum and the pharmacotoxicity of micellar system of Amphotericin B sodium desoxicholate in aqueous solutions before and after heat treatment. The both samples was subsequently diluted at four different concentrations (50 mg.L-1, 5 mg.L-1, 0.5 mg.L-1 and 0.05mg.L-1) for performed scanning spectra and pharmacotoxicity assay; two cell models were used for the experiments: Red Blood Cells (RBC) from human donnors and Candida parapisilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC were the parameters used to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-H were assessed by K+ leakage or cell survival rate from Cp. The spectral study showed that aggregate peak of Amphotericin B sodium desoxicholate (AmB-DOC) at 327nm changed from 323nm for Heated Amphotericin B (AmB-H). Concerning the toxicity, AmB-DOC and AmB-H showed different behavior: the hemoglobin leakage for AmB-DOC, at high concentrations, was higher than AmB-H, whose values tended to zero. Similar profile was found in both for the K+ leakage (p<0,05). About activity, AmB-H keeps the same features than AmB-DOC. In short, the AmB-H demonstrated to be much less toxic than AmB-DOC and remains same activity against fungal cell highlighting the importance of this new procedure as a simple, inexpensive and safe alternative for the future treatment of systemic fungal infections.