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Design and Characterization of Chitosan Nanoformulations for the Delivery of Antifungal Agents.

ABSTRACT: Among different Candida species triggering vaginal candidiasis, Candida albicans is the most predominant yeast. It is commonly treated using azole drugs such as Tioconazole (TIO) and Econazole (ECO). However, their low water solubility may affect their therapeutic efficiency. Therefore, the aim of this research was to produce a novel chitosan nanocapsule based delivery system comprising of TIO or ECO and to study their suitability in vaginal application. These systems were characterized by their physicochemical properties, encapsulation efficiency, in vitro release, storage stability, cytotoxicity, and in vitro biological activity. Both nanocapsules loaded with TIO (average hydrodynamic size of 146.8 ± 0.8 nm, zeta potential of +24.7 ± 1.1 mV) or ECO (average hydrodynamic size of 127.1 ± 1.5 nm, zeta potential of +33.0 ± 1.0 mV) showed excellent association efficiency (99% for TIO and 87% for ECO). The analysis of size, polydispersity index, and zeta potential of the systems at 4, 25, and 37 °C (over a period of two months) showed the stability of the systems. Finally, the developed nanosystems presented fungicidal activity against C. albicans at non-toxic concentrations (studied on model human skin cells). The results obtained from this study are the first step in the development of a pharmaceutical dosage form suitable for the treatment of vaginal candidiasis.

SUBMITTER: Calvo NL

PROVIDER: S-EPMC6695956 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction:In the last years, the utilization of phytomedicines has increased given their good therapeutic activity and fewer side effects compared to allopathic medicines. However, concerns associated with the biocompatibility and toxicity of natural compounds, limit the phytochemical therapeutic action, opening the opportunity to develop new systems that will be able to effectively deliver these substances. This study has developed a nanocomposite of chitosan (CS) functionalized with graphene oxide (GO) for the delivery of proanthocyanidins (PAs), obtained from a grape seed extract (Ext.). Methods:The GO-CS nanocomposite was covalently bonded and was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM) and by dynamic light scattering (DLS). The loading and release of Ext. from the GO-CS nanocomposite were performed in simulated physiological, and the cytotoxicity of the raw materials (GO and Ext.) and nanocomposites (GO-CS and GO-CS-Ext.) was determined using a human kidney cell line (HEK 293). Results:The chemical characterization indicated that the covalent union was successfully achieved between the GO and CS, with 44 wt. % CS in the nanocomposite. The GO-CS nanocomposite was thermostable and presented an average diameter of 480 nm (by DLS). The Ext. loading capacity was approximately 20 wt. %, and under simulated physiological conditions, 28.4 wt.% Ext. (g) was released per g of the nanocomposite. GO-CS-Ext. was noncytotoxic, presenting a 97% survival rate compared with 11% for the raw extract and 48% for the GO-CS nanocomposite at a concentration of 500 µg mL-1 after 24 hrs. Conclusion:Due to ?-? stacking and hydrophilic interactions, GO-CS was reasonably efficient in binding Ext., with high loading capacity and Ext. release from the nanocomposite. The GO-CS nanocomposite also increased the biocompatibility of PAs-rich Ext., representing a new platform for the sustained release of phytodrugs.

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Design and Characterization of Chitosan Nanoformulations for the Delivery of Antifungal Agents.

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