title: Clotrimazole-loaded nanostructured lipid carrier hydrogels: thermal analysis and in vitro studies.
abstract: The aim of the present work is to design a new formulation containing clotrimazole (CTZ) loaded into nanostructured lipid carriers (NLC) for the treatment of fungal vaginal infections. In order to obtain formulations with suitable viscosity for mucosal application, NLC containing CTZ produced by the ultrasonication method were viscosized by the addition of poloxamer P407 in the NLC dispersion (CTZ-NLC-gel). These systems exhibit well-known thermogelling properties. The rheological characterization of the CTZ-NLC hydrogel using a controlled stress rheometer evidenced that the presence of NLC or CTZ did not affect gelling temperature (Tgel). Dilution with simulated vaginal fluid (SVF) increased the Tgel from 17.4 to 29.6°C. For these thermogelling systems, micro-calorimetric assays conducted by a Micro-DSC III confirmed that the hydrogel-containing CTZ-NLC was able to change its structure with a rapid passage from non-crystalline (liquid) to crystalline (semi-solid) form. Furthermore, when a local application is considered, no drug should pass through the vaginal mucosa, limiting thus the systemic diffusion and toxicity. For this purpose, Franz cell has been employed to investigate the ex vivo permeation of CTZ through pig vaginal mucosa. The results showed no CTZ diffusion. The toxicological experiments performed on HeLa cells after a 24h incubation time confirmed that CTZ-NLC-gel at a concentration of 1mg/mL showed a low toxicity profile resulting in a cell vitality of 77.2%. Interestingly, anti-candida activity studies demonstrated that CTZ-NLC gel was 4-fold more active than Fungizone(®) against Candida albicans. These encouraging results suggest that the hydrogel containing CTZ-NLC could be proposed as an innovative system to administer CTZ to treat vaginal infections.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ravani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Esposito
authors.forename: Christian
authors.initials: C
authors.lastname: Bories
authors.forename: Vanessa Lievin-Le
authors.initials: VL
authors.lastname: Moal
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Madeleine
authors.initials: M
authors.lastname: Djabourov
authors.forename: Rita
authors.initials: R
authors.lastname: Cortesi
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003022:Clotrimazole / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009092:Mucous Membrane / Q000378:metabolism; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D013552:Swine; D014621:Vagina / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D020100:Hydrogels; D008055:Lipids; D020442:Poloxamer; D003022:Clotrimazole
keywords: Antifungal activity; Candida albicans; Clotrimazole; Gel; Nanostructured lipid carriers (NLC); Vaginal administration