Development and evaluation of exemestane-loaded lyotropic liquid crystalline gel formulations

摘要

>Introduction: The use of liquid crystalline (LC) gel formulations for drug delivery has considerably improved the current delivery methods in terms of bioavailability and efficacy. The purpose of this study was to develop and evaluate LC gel formulations to deliver the anti-cancer drug exemestane through transdermal route. >Methods: Two LC gel formulations were prepared by phase separation coacervation method using glyceryl monooleate (GMO), Tween 80 and Pluronic® F127 (F127). The formulations were characterized with regard to encapsulation efficiency (EE), vesicle size, Fourier transform infrared (FTIR) spectroscopy, surface morphology (using light and fluorescence microscopy), in vitro release, ex vivo permeation, in vitro effectiveness test on MDA-MB231 cancer cell lines and histopathological analysis. >Results: Results exhibited that the EE was 85%-92%, vesicle size was 119.9-466.2 nm while morphology showed spherical vesicles after hydration. An FTIR result also revealed that there was no significant shift in peaks corresponding to Exemestane and excipients. LC formulations release the drug from cellulose acetate and Strat-MTM membrane from 15%-88.95%, whereas ex vivo permeation ranges from 37.09-63%. The in vitro effectiveness study indicated that even at low exemestane concentrations (12.5 and 25 μg/mL) the formulations were able to induce cancer cell death, regardless of the surfactant used. Histopathological analysis thinning of the epidermis as the formulations penetrate into the intercellular regions of squamous cells. >Conclusion: The results conjectured that exemestane could be incorporated into LC gels for the transdermal delivery system and further preclinical studies such as pharmacokinetic and pharmacodynamic studies will be carried out with suitable animal models.