Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: Pharmacokinetic and biochemical assessment.
Hydroxyapatite based biodegradable mPEG-PLGA nanoparticles of risedronate (mPEG-PLGA-RIS-HA) were prepared by water miscible dialysis method for synergistic treatment of osteoporosis. The bone targeting potential of prepared nanoparticles was evaluated by performing the cell viability study and protein estimation in pre-osteoblast cell line (MC3T3E1). Biochemical and in-vivo pharmacokinetic studies on osteoporotic rat model treated with different formulations were performed. Under the biochemical study ALP, TRAP, HxP and Calcium levels were determined. Osteoporotic model treated with prepared nanoparticles indicated significant effect on bone. Pharmacokinetic studies revealed 6-fold and 4-fold increase in the relative bioavailability after intravenous and oral administration of nanoparticles respectively as compared to marketed formulation confirming better effective drug transport. Biochemical investigations also showed a significant change in biomarker level which ultimately lead to bone formation/resorption. A stability analysis has also been carried out according to ICH guidelines (Q1AR2) and shelf life was found to be 1year and 4 months for the prepared formulation. Thus the results of present studies indicated that mPEG-PLGA-RIS-HA NPs has a great potential for sustained delivery of RIS for the treatment and prevention of osteoporosis and to minimize the adverse effects of RIS typically induced by its oral administration.
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Purnima
P
Rawat
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Iqbal
I
Ahmad
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Shindu C
SC
Thomas
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Shweta
S
Pandey
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Divya
D
Vohora
Molecular Sciences Lab, National Institute of Immunology, New Delhi, New Delhi 110067, India.
Sarika
S
Gupta
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Farhan Jalees
FJ
Ahmad
Nanomedicine Research Lab., Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: stalegaonkar@gmail.com.
Sushama
S
Talegaonkar
D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010006:Osteoblasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011092:Polyethylene Glycols; D017886:Durapatite; D000068296:Risedronic Acid
Bioavailability; Biochemical; Nanoparticles; Osteoporosis; Pharmacokinetics; Risedronate