Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model

Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, D. Roy

doi:10.1016/j.ejps.2014.10.015

Cited by 68 publications

(38 citation statements)

References 35 publications

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“…In the FT-IR spectrum ( Figure 1B), the vibration peaks at 3,575 and 3,438 cm −1 were attributed to the O−H stretching vibration in HAp, and the vibration peaks at 564 and 610 cm −1 belonged to the asymmetric stretching vibration peaks of P−O in the PO 4 3− groups; these results were consistent with those of previous studies. 23,24 SEM revealed that the nanoparticles were homogeneous, needlelike crystals ( Figure 1C). …”

Section: Characterization and Morphology Observation Of Nano-hap Crysmentioning

confidence: 99%

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

Zhang¹,

Sun²,

Ouyang³

et al. 2017

IJN

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Objective This study aimed to investigate the damage mechanism of nanosized hydroxyapatite (nano-HAp) on mouse aortic smooth muscle cells (MOVASs) and the injury-inhibiting effects of diethyl citrate (Et 2 Cit) and sodium citrate (Na 3 Cit) to develop new drugs that can simultaneously induce anticoagulation and inhibit vascular calcification. Methods The change in cell viability was evaluated using a cell proliferation assay kit, and the amount of lactate dehydrogenase (LDH) released was measured using an LDH kit. Intracellular reactive oxygen species (ROS) and mitochondrial damage were detected by DCFH-DA staining and JC-1 staining. Cell apoptosis and necrosis were detected by Annexin V staining. Intracellular calcium concentration and lysosomal integrity were measured using Fluo-4/AM and acridine orange, respectively. Results Nano-HAp decreased cell viability and damaged the cell membrane, resulting in the release of a large amount of LDH. Nano-HAp entered the cells and damaged the mitochondria, and then induced cell apoptosis by producing a large amount of ROS. In addition, nano-HAp increased the intracellular Ca 2+ concentration, leading to lysosomal rupture and cell necrosis. On addition of the anticoagulant Et 2 Cit or Na 3 Cit, cell viability and mitochondrial membrane potential increased, whereas the amount of LDH released, ROS, and apoptosis rate decreased. Et 2 Cit and Na 3 Cit could also chelate with Ca + to inhibit the intracellular Ca 2+ elevations induced by nano-HAp, prevent lysosomal rupture, and reduce cell necrosis. High concentrations of Et 2 Cit and Na 3 Cit exhibited strong inhibitory effects. The inhibitory capacity of Na 3 Cit was stronger than that of Et 2 Cit at similar concentrations. Conclusion Both Et 2 Cit and Na 3 Cit significantly reduced the cytotoxicity of nano-HAp on MOVASs and inhibited the apoptosis and necrosis induced by nano-HAp crystals. The chelating function of citrate resulted in both anticoagulation and binding to HAp. Et 2 Cit and Na 3 Cit may play a role as anticoagulants in reducing injury to the vascular wall caused by nano-HAp.

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Section: Characterization and Morphology Observation Of Nano-hap Crysmentioning

confidence: 99%

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

Zhang¹,

Sun²,

Ouyang³

et al. 2017

IJN

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“…It was established that under conditions likely to stimulate bisphosphonate binding to the bone, ZOL has a superior binding affinity for bone HA crystals as compared to other bisphosphonates. Therefore, after intravenous injection, ZOL is swiftly cleared from the circulation and gets localized to the bone [7] .…”

Section: Research Papermentioning

confidence: 99%

“…Despite their therapeutic effects, bisphosphonates are currently used in various studies as suitable targeting agents in radiotherapy [4,5] . Previous studies from our laboratory and others have shown that bisphosphonates could be useful as drug bone targeted carriers for delivering various nanoparticle-based therapeutic interventions to bone tissues for skeletal-related diseases [6][7][8][9][10] . This approach prevents adverse effects such as toxicity due to non-specific tissue interactions, larger medicine dosages, higher costs, and even likely poor patient compliance towards therapy.…”

Section: Research Papermentioning

confidence: 99%

“…ZOL-loaded HA nanoparticles were prepared according to our previously reported method [7] . Briefly, HA nanoparticles were synthesized first by sol-gel method in which calcium nitrate tetrahydrate and phosphoric pentoxide were used with the molar ratio of 10:3.…”

Section: Preparation Of Bone Targeted Zol-loaded Ha Nanoparticlesmentioning

confidence: 99%

“…The formed gel was dried in an oven at 80° in the air for 24 h and then sintered at 600°. Adsorption method was employed for the preparation of ZOL-loaded HA nanoparticle-based formulation [7] .…”

Section: Preparation Of Bone Targeted Zol-loaded Ha Nanoparticlesmentioning

confidence: 99%

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Sensitive and Rapid RP-HPLC Quantification of Zoledronic Acid in a Hydroxyapatite-based Nanoparticles

Khajuria¹,

Razdan²

2017

pharmaceutical-sciences

Self Cite

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The aim of this study was to develop and validate a rapid and sensitive reverse-phase high performance liquid chromatography method for the quantitative determination of zoledronic acid in nanoparticles. The mobile phase was a mixture of methanol (30%) and 7 mM tetra butyl ammonium hydrogen sulphate, 2 mM di-sodium hydrogen orthophosphate and sulphate and 8 mM di-potassium hydrogen orthophosphate (70%), pH adjusted to 3 with trifluoroacetic acid. C18 column was used as a stationary phase. The flow rate was maintained at 1 ml/min. The detection of the constituents was done at 215 nm using an ultraviolet detector. Method validation was executed according to the International Conference on Harmonisation guidelines. The retention time of zoledronic acid was 3.27±0.03 min (n=6). The assay was linear over the concentration range of 200-800 μg/ml. The proposed method was sensitive with the limit of detection and limit of quantification values equal to 200 and 800 µg/ml, respectively. The method was accurate with percent mean recovery from 99.01±1.31 to 100.80±0.094% and precise as percent relative standard deviation values were less than 1%. The method was successfully applied for the estimation of zoledronic acid loading efficiency on hydroxyapatite nanoparticles and in vitro zoledronic acid release profile analysis in hydroxyapatite-based nanoparticles.

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Nanomaterials for Tissue Grafting

Singh¹,

Kotal²,

Chowdhury³

2022

Nanomaterials in Clinical Therapeutics

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Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model

Cited by 68 publications

References 35 publications

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

Sensitive and Rapid RP-HPLC Quantification of Zoledronic Acid in a Hydroxyapatite-based Nanoparticles

Nanomaterials for Tissue Grafting

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