Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting.

OBJECTIVES: This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting.

METHODS: Liposomes were formulated by dehydration-rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading.

KEY FINDINGS: Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression.

CONCLUSIONS: Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.