Sodium alginate in oil-poloxamer organogels for intravaginal drug delivery: Influence on structural parameters, drug release mechanisms, cytotoxicity and in vitro antifungal activity

• DOI: 10.1016/j.msec.2019.02.036
• Publication Date: 2019-02-21T17:02:50Z
• Authors: Samyr M. Querobino; Naially C. de Faria; Aryane A. Vigato; Bruna G.M. da Silva; Ian P. Machado; Maricilia S. Costa; Fanny N. Costa; Daniele R. de Araujo; Carlos Alberto-Silva
• Keywords: Antifungal Agents; Calorimetry, Differential Scanning; Cell Death; Alginates; Cell Survival; Temperature; Microbial Sensitivity Tests; Poloxamer; 02 engineering and technology; Phase Transition; 3. Good health; Administration, Intravaginal; Drug Liberation; Kinetics; Drug Delivery Systems; Chlorocebus aethiops; Animals; Humans; Rheology; 0210 nano-technology; Gels; Oils; HeLa Cells

Local administration of antimicrobial agents is the first therapeutic approach for the treatment of Candida albicans infections. The duration of contact of formulations with the vaginal mucosa is critical for therapeutic efficacy. This study describes the development of organogels employing an oil phase composed of oleic acid (OA) and an aqueous phase consisting of the poloxamer PL407, alone or in association with PL188, together with 0.25-1% sodium alginate (SA), in order to obtain an intravaginal drug delivery system capable of modulating the release of voriconazole (VRC). VRC was solubilized in oleic acid homogenized with the PL-SA aqueous phase, at a final concentration of 5 mg/mL. Physicochemical characterization was performed for evaluation of the influence of SA on organogel structural organization, biopharmaceutical properties, pharmacological efficacy, and cytotoxicity, envisaging use of the formulation for the treatment of vaginal candidiasis. The enthalpy variation values showed greater changes in the presence of PL188 and after the incorporation of SA or VRC in the organogels. Rheological analysis showed Tsol-gel values in the ranges 11-39 °C and 27-30 °C for the OA-PL407 and OA-PL407-188 formulations, respectively. Oscillatory analysis of OA-PL407-188 showed that G' was ~20-fold higher than G″, even after submitting the formulation to temperature variation. VRC-OA-PL407 showed fast drug release from 0.5 to 4 h, maintaining total release (~100%) up to 24 h. The incorporation of SA in the organogels enabled modulation of VRC release, with different release percentages for 0.25% SA (~75%), 0.5% SA (~55%), and 1% SA (~35%). The formulation was non-cytotoxic towards HeLa and Vero cell lines. In diffusion tests, it was able to prevent the growth of Candida albicans and Candida krusei. In conclusion, the results suggested that OA-PL407-188-SA organogels could be possible new systems for VRC delivery, with potential for use in future vaginal applications.