How can micelle systems be rebuilt by a heating process?

Abstract

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were then diluted at four different concentrations (50 mg · L −1 , 5 mg · L −1 , 0.5 mg · L −1 , and 0.05 mg · L −1 ) to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC) from human donors and Candida parapsilosis ( Cp ). While potassium (K + ) and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K + leakage and cell survival rate from Cp . The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg · L −1 ). For K + leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp ( P < 0.05). AmB-DOC-H and AmB-DOC also revealed a similar profile of activity against Cp with an equivalent survival rate. In short, AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as AmB-DOC against fungal cells. The results highlight the importance of this new procedure as a simple, inexpensive, and safe way to produce a new kind of micelle system for the treatment of systemic fungal infections.

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

“…Mild heating of Fungizone ® (20 min at 70 • C) was found to increase the thermodynamic stability of the formulation and to improve its therapeutic index by producing a super aggregated and less toxic form of AmB while retaining antifungal efficacy [57,[84][85][86][87][88][89][90]. Heat-induced superaggregation of AmB was shown to modify its distribution among the serum lipoproteins and to attenuate AmB-stimulated production of TNF-α and other pro-inflammatory mediators in human THP-1 monocytes in vitro [86,91], which may contribute to its reduced cytotoxicity against host cells in vivo in experimental animal mycoses [86,87,89,92].…”

A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis

“…These results indicate that the AmB entrapped inside of the hydrogel structure keeps its antifungal activity, just as free AmB, while the PVA–H did not show any antifungal activity, corroborating with the idea that AmB stands with its pharmacological activity unaltered and the residual cross-linking quantities were negligible to show antifungal activity or severe cytotoxicity. It has been reported that the affinity of AmB to the ergosterol on fungi membranes is strongly dependent on its aggregation state [80,81]. This phenomenon could be the main reason behind the enhanced antifungal activity of PVA–AmB compared to the free form of the drug.…”

Influence of Eugenia uniflora Extract on Adhesion to Human Buccal Epithelial Cells, Biofilm Formation, and Cell Surface Hydrophobicity of Candida spp. from the Oral Cavity of Kidney Transplant Recipients

“…Hemolytic activity was performed according to Silva-Filho et al [ 64 ] with some modifications. A healthy adult donor provided blood for the in vitro experiments.…”