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Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery

Authors Jaji AZ, Bakar MZBA, Mahmud R, Loqman MY, Hezmee MNM, Isa T, Wenliang F, Hammadi NI

Received 18 May 2016

Accepted for publication 9 August 2016

Published 18 January 2017 Volume 2017:10 Pages 23—33

DOI https://doi.org/10.2147/NSA.S113030

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Professor Israel (Rudi) Rubinstein


Alhaji Zubair Jaji,1,2 Md Zuki Bin Abu Bakar,1,3 Rozi Mahmud,4 Mohamad Yusof Loqman,5 Mohamad Noor Mohamad Hezmee,1 Tijani Isa,3 Fu Wenliang,3 Nahidah Ibrahim Hammadi1

1Department of Veterinary Pre-Clinical Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ilorin, Ilorin, Kwara, Nigeria; 3Molecular Biomedicine Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 4Department of Imaging, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

Abstract:
Calcium carbonate is a porous inorganic nanomaterial with huge potential in biomedical applications and controlled drug delivery. This study aimed at evaluating the physicochemical properties and in vitro efficacy and safety of cockle shell aragonite calcium carbonate nanocrystals (ANC) as a potential therapeutic and hormonal delivery vehicle for osteoporosis management. Free and human recombinant parathyroid hormone 1-34 (PTH 1-34)-loaded cockle shell aragonite calcium carbonate nanocrystals (PTH-ANC) were synthesized and evaluated using standard procedures. Transmission electron microscopy and field emission scanning electron microscopy results demonstrated highly homogenized spherical-shaped aragonite nanocrystals of 30±5 nm diameter. PTH-ANC had a zeta potential of −27.6 ± 8.9 mV. The encapsulation efficiency of the formulation was found to be directly proportional to the concentrations of the drug fed. The X-ray diffraction patterns revealed strong crystallizations with no positional change of peaks before and after PTH-ANC synthesis. Fourier transform infrared spectroscopy demonstrated no detectable interactions between micron-sized aragonite and surfactant at molecular level. PTH-ANC formulation was stabilized at pH 7.5, enabling sustained slow release of PTH 1-34 for 168 h (1 week). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytocompatibility assay in Human Foetal Osteoblast Cell Line hFOB 1.19 showed that ANC can safely support osteoblast proliferation up to 48 h whereas PTH-ANC can safely support the proliferation at 72 h and beyond due to the sustained slow release of PTH 1-34. It was concluded that due to its biogenic nature, ANC is a cytocompatible antiosteoporotic agent. It doubles as a nanocarrier for the enhancement of efficacy and safety of the bone anabolic PTH 1-34. ANC is expected to reduce the cost, dosage, and dose frequency associated with the use of PTH 1-34 management of primary and secondary forms of osteoporosis.

Keywords: bone, FESEM, FT-IR, MTT viability, PTH 1-34, sustained release, TEM, XRD, zeta potential

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