title: Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model.
abstract: We investigated the potential of using novel zoledronic acid (ZOL)-hydroxyapatite (HA) nanoparticle based drug formulation in a rat model of postmenopausal osteoporosis. By a classical adsorption method, nanoparticles of HA loaded with ZOL (HNLZ) drug formulation with a size range of 100-130nm were prepared. 56 female Wistar rats were ovariectomized (OVX) or sham-operated at 3months of age. Twelve weeks post surgery, rats were randomized into seven groups and treated with various doses of HNLZ (100, 50 and 25μg/kg, intravenous single dose), ZOL (100μg/kg, intravenous single dose) and HA nanoparticle (100μg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. After three months treatment period, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for trabecular microarchitecture. Sensitive biochemical markers of bone formation and bone resorption in serum were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the therapy with HNLZ drug formulation was more effective than ZOL therapy in OVX rats. Moreover, HNLZ drug therapy preserved the trabecular microarchitecture better than ZOL therapy in OVX rats. Furthermore, the HNLZ drug formulation corrected increase in serum levels of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin, tartrate-resistant acid phosphatase 5b and C-telopeptide of type 1 collagen better than ZOL therapy in OVX rats. The results strongly suggest that HNLZ novel drug formulation appears to be more effective approach for treating severe osteoporosis in humans.
authors.affiliation: Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore 560027, India; Laboratory for Integrative Multiscale Engineering Materials and Systems, Department of Aerospace Engineering, Indian Institute of Science, Bangalore 560012, India. Electronic address: deepak_kumarkhajuria@yahoo.co.in.
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Khajuria
authors.affiliation: Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore 560027, India.
authors.forename: Rema
authors.initials: R
authors.lastname: Razdan
authors.affiliation: Laboratory for Integrative Multiscale Engineering Materials and Systems, Department of Aerospace Engineering, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Debiprosad Roy
authors.initials: DR
authors.lastname: Mahapatra
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000737:chemistry*; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D053758:Nanoparticles / Q000737:chemistry*; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D017886:Durapatite
keywords: Hydroxyapatite nanoparticles; Postmenopausal osteoporosis; Rat model; Zoledronic acid