Publication: Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis
Authors
Manca, Maria Letizia ; Usach, Iris ; Esteban Peris, José ; Ibba, Antonella ; Orrù, Germano ; Valenti, Donatella ; Escribano-Ferrer, Elvira ; Gomez-Fernandez, Juan Carmelo ; Maria Fadda, Anna ; Manconi, Maria ; Aranda Martínez, Francisco José
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Publisher
MDPI
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DOI
https://doi.org/10.3390/pharmaceutics11060263
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info:eu-repo/semantics/article
Description
©2019. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/
This document is the Published, version of a Published Work that appeared in final form in Pharmaceutics. To access the final edited and published work see https://doi.org/10.3390/pharmaceutics11060263
Abstract
New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole
in a high amount (10 mg/mL), were obtained for the first time in this work by significantly
reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol
(≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition
of the hydrating medium and the concentration of the phospholipid on the physico-chemical
properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were
selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical
characterization performed using transmission electron microscopy (TEM), cryogenic transmission
electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the
formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of
forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of
the dispersion with water reduced the interactions between vesicles, leading to the formation of single
unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed
an improved drug deposition in the skin strata provided by the three-dimensionally-structured
vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles
were highly biocompatible and showed a significant antifungal activity in vitro, greater than the
commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the
reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results,
clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most
innovative and promising formulations for the treatment of candidiasis infections.
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Citation
Pharmaceutics 2019, 11, 263
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