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Design and Development of Bioceramic Based Functionalized PLGA Nanoparticles of Risedronate for Bone Targeting: In-vitro Characterization and Pharmacodynamic Evaluation

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Abstract

Purpose

Bioceramic(Hydroxyapatite) based Poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG) nanoparticles of Risedronate was prepared by dialysis method for bone-targeting.

Methods

Risedronate, a targeting moiety that has a strong affinity for bone, was conjugated to PLGA via carbodiimide chemistry. Mono-methoxy PEG(mPEG)-PLGA block polymers were synthesized and used to impart surface hydrophilicity to nanoparticles to avoid its uptake by reticuloendothelial system (RES). The structure of prepared di block copolymers were characterized by FT-IR and NMR spectrometry. Risedronate was adsorbed on the surface of hydroxyapatite (RIS-HA) and it was conjugated with different ratios of mPEG-PLGA. The formation of surface-modified PLGA nanoparticle prepared with various ratios of risedronate as well as hydroxyapatite and mPEG was confirmed by 1H NMR and FT-IR spectrometry.

Results

Size and % entrapment of the prepared nanoparticle was found to be 79.3 ± 2.3 nm and 93 ± 3.1%. Transmission electron microscopy (TEM) revealed that mPEG-PLGA-RIS-HA nanoparticles possess smooth and uniform surface. Pharmacodynamic study was performed on Dexamethasone (DEX) induced osteoporotic model. The effect of various formulations (mPEG-PLGA-RIS, mPEG-PLGA-RIS-HA and RISOFOS tablet) on bone was studied by Volume bone density (VBD) and by histopathological evaluation. Interestingly mPEG-PLGA-RIS-HA, showed a significant enhancement in bone micro-architecture when compared with other formulations.

Conclusions

The results strongly implicated that mPEG-PLGA-RIS-HA has a therapeutic benefits over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model.

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Abbreviations

CaP:

Calcium phosphate

DCC:

Dicyclohexyl carbodiimide

DEX:

Dexamethasone

DLS:

Dynamic light scattering

DMSO:

Dimethyl sulfoxide

HA:

Hydroxyapatite

mPEG:

Methoxy polyethylene glycol

NHS:

N-hydroxyl succinimide

PLGA:

Poly(D,L-lactide-co-glycolide)

RIS:

Risedronate

VBD:

Volumetric bone density analysis

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors are thankful for the financial assistance from ICMR, New Delhi. We also acknowledge the Evonik Research for providing the gift sample of PLGA (50:50) polymer and lipoid for providing the gift sample of methoxy PEG. The authors are also thankful to Mr. Jitender singh, Department of Pharmaceutical chemistry Jamia Hamdard and Dr. Ambrish Tiwari, Incharge of animal house, Faculty of Science, Jamia Hamdard, New Delhi for their inputs regarding animal studies.

Conflicts of Interest

The authors state no conflicts of interest

Author information

Authors and Affiliations

  1. Nanomedicine Research Lab, Department of Pharmaceutics Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India

    Purnima Rawat, Farhan Jalees Ahmad & Sushama Talegaonkar

  2. Molecular Sciences Lab, National Institute of Immunology, New Delhi, New Delhi, 110067, India

    Kapil Manglani & Sarika Gupta

  3. Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India

    Abul kalam & Divya Vohora

Authors
  1. Purnima Rawat
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  2. Kapil Manglani
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  3. Sarika Gupta
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  4. Abul kalam
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  5. Divya Vohora
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  6. Farhan Jalees Ahmad
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  7. Sushama Talegaonkar
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Correspondence to Sushama Talegaonkar.

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Rawat, P., Manglani, K., Gupta, S. et al. Design and Development of Bioceramic Based Functionalized PLGA Nanoparticles of Risedronate for Bone Targeting: In-vitro Characterization and Pharmacodynamic Evaluation. Pharm Res 32, 3149–3158 (2015). https://doi.org/10.1007/s11095-015-1692-4

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  • DOI: https://doi.org/10.1007/s11095-015-1692-4

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