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

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.

Fabrication of Bone Scaffolds from Cockle Shell Waste

“…There are different phases between scaffolds with and without the cockle shell powder. Jaji et al [2] and Lopez-Heredia et al [33] found similar results where the purity and crystallinity of CaCO 3 in the scaffolds were maintained even with the addition of other polymers. 2 a shows an amorphous structure where broad peaks appeared around 13.3°and 21.8°.…”

“…The results also demonstrate that the purity of CaCO 3 in the scaffolds was not affected by the existence of SA. Jaji et al [2] and Lopez-Heredia et al [33] found similar results where the purity and crystallinity of CaCO 3 in the scaffolds were maintained even with the addition of other polymers. On the contrary, SA scaffold displayed bands around 3336, 1585, 1407, and 1025 cm -1 .…”

“…Bone defects and irregularities may be caused by traumatic injuries or pathological conditions such as osteoporosis and bone cancer [1][2][3]. In today's medical practices, conventional treatment methods like autograft and allograft are used to treat the defects.…”

Cockle Shell-Derived Calcium Carbonate (Aragonite) Nanoparticles: A Dynamite to Nanomedicine

“…They can be produced using different types of biocompatible materials [5,6]. The use of nanoparticle-based drug carrier systems in the field of nanotechnology has become an area with a novel attention in the past few decades due to their unique and superior properties that enable functionalisation at both molecular and cellular levels [7][8][9][10][11][12][13][14]. Advanced novel drug delivery systems help to boost the efficacy of therapeutic drugs as well as minimising the rate of a drug's off targeted effects thereby preventing cytotoxicity to normal cells [8].…”

“…Cockle (Anadara granosa) with a Malaysian native name "kerang" belongs to the family of Cardiidae, which is a small, salt water edible clam that is popularly referred to as marine bivalve mollusc [11]. It is native to coastal regions of South East Asia (Malaysia, Thailand and Indonesia).…”