Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: Pharmacokinetic and biochemical assessment

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• 作者：Purnima Rawat^a ; Iqbal Ahmad^a ; Shindu C. Thomas^a ; Shweta Pandey^a ; Divya Vohora^b ; Sarika Gupta^c ; Farhan Jalees Ahmad^a ; Sushama Talegaonkar^a ; ^{stalegaonkar@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NP ; Nanoparticle ; BPs ; Bisphosphonates ; GIT ; Gastro intestinal tract ; HA ; Hydroxyapatite ; PLGA ; Poly(lactide-co-glycolide) ; ODDS ; Osteotropic drug delivery systems ; AA ; Ascorbic acid ; GP ; β-glycerophosphate ; ALP ; Alkaline Phosphatase ; TRAP ; Tartrate resistant acid Phosphatase ; HxP ; Hydroxyproline ; Ca ; Calcium ; I.V. ; Intravenously ; OCPC ; o-Cresolphthalein-Complexone ; nm ; Nanometer ; Nm ; Nanomoles ; mM ; Millimoles ; α-MEM ; α-Minimal essential medium ; mV ; Millivolt ; RH ; Relative Humidity
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：506
• 期：1-2
• 页码：253-261
• 全文大小：1183 K

文摘

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.