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

•Thermosensitive gel of metformin offered sustained release through vaginal route.•Metformin regulated the hormones in experimental polycystic ovary syndrome.•Intravaginal metformin administration surmounted the biopharmaceutical limitations.

Background and objectiveMetformin 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 (500 mg 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 resultsMTF-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.ConclusionIn conclusion, MTF-C-SUNs-Gel has paved the way for developing intravaginal dosage form of MTF-HCl for the treatment of PCOS.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide