title: 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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  In conclusion, MTF-C-SUNs-Gel has paved the way for developing intravaginal dosage form of MTF-HCl for the treatment of PCOS.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab), India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Saini
authors.affiliation: Department of Pharmacology, Chandigarh College of Pharmacy, Mohali (Punjab), India.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Sodhi
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab), India.
authors.forename: Lotika
authors.initials: L
authors.lastname: Bajaj
authors.affiliation: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab), India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali (Panjab), India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D000818:Animals; D002412:Cations; D048271:Chitosan / Q000737:chemistry; D065546:Drug Liberation; D005260:Female; D005782:Gels / Q000737:chemistry*; D005994:Glycerophosphates / Q000737:chemistry; D006728:Hormones / Q000097:blood; D008081:Liposomes; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D009093:Mucus / Q000187:drug effects; D010316:Particle Size; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017208:Rats, Wistar; D055672:Static Electricity; D034421:Sus scrofa; D013696:Temperature; D014783:Viscosity
chemical_list: D002412:Cations; D005782:Gels; D005994:Glycerophosphates; D006728:Hormones; D008081:Liposomes; D048271:Chitosan; D008687:Metformin
keywords: Cationic niosomes; Metformin hydrochloride; Polycystic ovary syndrome; Sustained release; Thermosensitive gel