Formulation of

Leuprolide acetate (LPA), a GnRH analogue, is drug of choice for treatment of uterine fibroids and endometriosis. The current marketed formulations of LPA show severe systemic side effects. This project aims to formulate LPA loaded liposomes to be administered by vaginal route for uterine targeting. Liposomes were prepared by thin film hydration method using 1:1 M ratio of DSPC: Cholesterol and characterized for vesicle size, zeta potential, entrapment efficiency, and loading. Radiolabeling of LPA was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc-labeled complexes was assessed by diethylenetriaminepentaacetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation via vaginal route. Spherical and discrete vesicles of size 189 nm were seen in TEM results with entrapment efficiency and loading of 74.36% and 9.29%w/w, respectively. Liposomes were able to sustain the drug release for 5 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes concentrated and were retained within the uterus for a longer period of time. Uterine targeting of liposomal LPA indicates its potential to overcome the limitations of presently available formulations. Hence, this seems to be a promising approach for targeting the drugs, whose site of action is uterus.