Intravaginal administration of metformin hydrochloride loaded cationic niosomes amalgamated with thermosensitive gel for the treatment of polycystic ovary syndrome: In vitro and in vivo studies.

Background And Objective: Metformin hydrochloride (MTF-HCl) is extensively recommended by physicians for the treatment of polycystic ovary syndrome (PCOS). Mechanistically, MTF-HCl activates AMP-dependent kinase-α (AMPK-α) pathway to decrease the glucose production, enhances fatty acid oxidation and elevates the uptake of glucose in tissues. However, despite favourable physicochemical properties, oral administration of MTF-HCl is associated with impaired bioavailability (50-60%), lactic-acidosis and frequent dosing (500mg 2-3 times a day) in PCOS that ultimately influence the patient compliance. Therefore, in present investigation, MTF-HCl loaded unmodified and cationic small unilamellar niosomes were separately amalgamated with thermosensitive gel (MTF-HCl-SUNs-Gel and MTF-HCl-C-SUNs-Gel) for the treatment of PCOS through vaginal route of administration.

Methods And Results: MTF-HCl-SUNs and MTF-HCl-C-SUNs were separately prepared by reverse phase evaporation method. The nanovesicle size and zeta-potential of MTF-HCl-C-SUNs were measured to be 210.3±14.8-nm (P<0.05) and +8.7±2.7-mV (P<0.001), significantly higher than 198.5±20.3-nm and -16.6±3.9-mV of MTF-HCl-SUNs, respectively. Moreover, promising results of in vitro characterization parameters like gelation time, gelling temperature, viscosity analysis, percent mucoadhesiveness and drug release of MTF-HCl-C-SUNs-Gel and MTF-HCl-SUNs-Gel ensured the candidature of tailored gels for further in vivo investigations. In this way, treatment of PCOS rats under scheduled dose-dosage regimen with oral MTF-HCl solution, intravaginal MTF-HCl-SUNs-Gel and intravaginal MTF-HCl-C-SUNs-gel exhibited remarkable alterations, recruitment and development of normal follicles in addition to normalization of level of various hormones in PCOS.

Conclusion: In conclusion, MTF-C-SUNs-Gel has paved the way for developing intravaginal dosage form of MTF-HCl for the treatment of PCOS.