Preparation, characterization, and evaluation of amphotericin B-loaded MPEG-PCL-g-PEI micelles for local treatment of oral <em>Candida albicans</em>

Abstract

Fatal Candida albicans infections in the mucosal system can occur in association with immune-compromised diseases and dysbacteriosis. Currently, amphotericin B (AmB) is considered to be the most effective antibiotic in the treatment of C. albicans infections, but its clinical application is limited by side effects and poor bioavailability. In order to use AmB in the local treatment of oral C. albicans infections, AmB/MPEG-PCL-g-PEI (monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-graft-polyethylenimine, MPP) micelles were prepared. A series of characterizations were performed. The micelles allowed a sustained in vitro release in both normal oral conditions (pH 6.8) and C. albicans infection conditions (pH 5.8). Then, buccal tablets containing freeze-dried powder of AmB/MPP micelles were produced by direct compression process and evaluated as regards to weight variation, hardness, and friability. In vitro drug release of the buccal tablets was measured in both the United States Pharmacopeia dissolution apparatus and the dissolution rate test apparatus, which was previously designed for simulating in vivo conditions of the oral cavity. The buccal tablets could sustainably release within 8 h and meet the antifungal requirements. Regarding safety assessment of AmB/MPP micelles, in vivo histopathological data showed no irritation toward buccal mucosa of the rats in both optical microscopy and ultrastructure observation of the tissues. MTT experiment proved that AmB/MPP micelles reduced the cytotoxicity of AmB. The micelles delivered through the gastrointestinal route were also found to be non-systemic toxicity by liquid chromatography-mass spectrometry analysis. Furthermore, the antifungal action of AmB/MPP micelles was evaluated. Although AmB/MPP had no obvious improvement as compared to AmB alone in the antifungal effect on planktonic C. albicans , the micelles significantly enhanced the antifungal activity against the biofilm state of C. albicans . Thus, it was concluded that AmB/MPP micelles represent a promising novel drug delivery system for the local treatment of oral C. albicans infections.

Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis

“…3A and B shows the thermal behavior of AmB, Dex FD, Dex-AmB FD, Dex SD and Dex-AmB SD in the range 25-235°C. As described in the literature, AmB was characterized by a double endothermic peak [39,44], here determined at 165.9 (melting point of AmB crystal) and 199.5°C whereas Dex FD (Fig. 3A) and Dex SD (Fig.…”

Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections

“…It should be noted that blank formulations were not introduced in the assay as negative controls because it was expected that PCL and other related polymer-based formulations would have no significant effects or activity when used alone. This hypothesis was also supported by the already published literature discussing PCL-based as well as other polymer-based formulations of Amp B and for other drugs where no negative control of the polymeric nanoparticles was used, as discussed elsewhere [34][35][36]. Additionally, studies using PCL-based drug formulations, where polymeric nanoparticles were used as negative controls, reported no significant effects or activities of these negative controls, as reported for Sertaconazole [37].…”

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

“…Kenechukwu et al investigated a miconazole nitrate-loaded nano lipid gel which possessed desirable stability, readability as well as better prolonged release and anti-fungal properties [191]. Zhou et al prepared AmB/MPEG-PCL-g-PEI (amphotericin B/monomethoxypoly (ethylene glycol)-poly (epsilon-caprolactone) -graft-polyethylenimine, MPP) micelles loaded tablet with 8-h slow release, reduced cytotoxicity, and improved anti-biofilm effect in vitro [192].…”