title: A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits.
abstract: BACKGROUND
  Raloxifene hydrochloride (RLH), a selective estrogen receptor modulator, shows antiproliferative and apoptotic effects on Leiomyoma. Its extensive first pass metabolism leads to oral bioavailability of 2%.
  
  
  OBJECTIVE
  The aim of this investigation was to formulate RLH-loaded liposomes and study its uterine-targeting efficiency after intravaginal administration.
  
  
  METHODS
  Liposomes were prepared by thin film hydration method using 1:1 molar ratio of DSPC:Cholesterol and characterized for vesicle size, zeta potential, %entrapment efficiency, loading, drug release and transmission electron microscopy. Radiolabeling of RLH was performed with reduced technetium-99m (99mTc). Binding affinity of99mTc-labeled complexes was assessed by diethylene triamine penta acetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation intravaginally.
  
  
  CONCLUSIONS
  Spherical and discrete liposomes of size 119 nm were seen in TEM results. Liposomes had high entrapment efficiency of 90.96% with drug loading of 27.25%w/w. Liposomes were able to sustain the drug release for 6 days.99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes were concentrated and retained within the uterus for a longer period of time.
  
  
  CONCLUSIONS
  Uterine targeting of RLH-loaded liposomes indicates its potential to overcome the limitations of marketed formulation. Drug targeting to site of action anticipates dose reduction needed to elicit the therapeutic effect.
authors.affiliation: a Shri G.H. Patel Pharmacy Building, Centre for Postgraduate Studies in Pharmacy, TIFAC Core in NDDS , Vadodara , Gujarat , India and.
authors.forename: Arpita
authors.initials: A
authors.lastname: Patel
authors.affiliation: b Institute of Nuclear Medicine and Allied Sciences , Delhi , India.
authors.forename: Amit
authors.initials: A
authors.lastname: Tyagi
authors.affiliation: b Institute of Nuclear Medicine and Allied Sciences , Delhi , India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: a Shri G.H. Patel Pharmacy Building, Centre for Postgraduate Studies in Pharmacy, TIFAC Core in NDDS , Vadodara , Gujarat , India and.
authors.forename: Hetal
authors.initials: H
authors.lastname: Thakkar
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D001682:Biological Availability; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D005260:Female; D005720:Gamma Rays; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D011817:Rabbits; D011877:Radionuclide Imaging / Q000379:methods; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry; D014018:Tissue Distribution; D014599:Uterus / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D020849:Raloxifene Hydrochloride; D013667:Technetium; D002784:Cholesterol
keywords: Biodistribution; fibroids; lipophilic; scintigraphy; small unilamellar vesicles