Preparation and In vitro Characterization of Antiparasitic Formulations for Mucosal Administration
Project no. 293 · Status: Kapanmış · 2018
Summary
The aim of this study was to develop and characterize vaginally administered formulations for treatment of infections caused by parasitic protozoa, Trichomonas vaginalis containing combination of first choice drug metronidazole and natural compound, curcumin / nanocurcumin. Combination therapies are now utilized to treat many diseases, starting from cancer to many parasite infections, since it is more effective and affordable than mono- therapy. Combination therapies are believed to represent a new explorable strategy for Trichomonas vaginalis. In this respect, poloxamer gel formulations containing metronidazol and curcumin combination were evaluated and optimized by Box-Behnken statistical experiment design concept. Poloxamer gels are known for exhibiting similar properties to those of biological tissues and preserving their mechanical integrity during their usage. Additionally, vaginaly applied poloxamer gels are able to bypass the toxic effects of systemic treatment of T.vaginalis and ensure direct contact with the pathogen. In the scope of the experimental design, formulations have been optimized by assessing the impact of critical parameters over critical quality characteristics (sol-gel transition temperature, dissolution capacity of active substances, plastic viscosity, dynamic viscosity and threshold values of shear stresses). In addition optimized formulations (OPT F1-F2-F3) were evaluated in terms of their mechanical properties, in vitro release properties and cytotoxicity over the SK-HEP-1 cell line. As a result of these studies, it has been observed that the optimum formulations were not cytotoxic and exhibit features suitable for vaginal administration. In the second part of the thesis, in order to prevent its eventual degradation curcumin nanoparticles were prepared and optimized according to Box-Behnken experiment design. Physicochemical properties of the optimized CUR-NP formulation were characterized and the surface morphologies examined by SEM studies were found to be spherical and smooth. Than, optimum KurNp was incorporated in their final gel formulation along side with metronidazol. In the last stage of the thesis, the efficacy of ideal selected gel formulations (OPT-F2 and Met-KurNp-Jel) against T. vaginalis. Results showed statistically significant in vitro activity proven their antiparasitic activity. In addition, stability studies conducted at 4 ºC and 25 ºC conditions revealed that the selected ideal formulations remain stable until the end of 90 days. Our results showed that the developed OPT-F2 / Met-KurNp-Jel poloxamer base in situ gel formulation intended for local vaginal applications can offer an innovative approach for the treatment of trichomoniasis, and can also contribute to scientific research to advance this knowledge area. Keywords; Trichomonas vaginalis; Curcumin; Metronidazole; Poloxamer gel; Polymeric Nanoparticle