Nashrieh Shimi va Mohandesi Shimi Iran

Nashrieh Shimi va Mohandesi Shimi Iran

Design and Synthesis of Efficient New Nanocomposites Fe3O4@MCM-41/HAP/APTES and CMC/MMT/HAP for Controlled Release Drug Delivery: Targeted Delivery of Teriparatide in Bone Tissue Engineering

Document Type : Research Article

Authors
1 Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran, IR. IRAN
2 Department of Chemistry, Amirkabir University of Technology. Tehran, I.R. IRAN
3 Guilan Road Trauma Research Center, Guilan University of Medical Sciences Rasht. I.R. IRAN
Abstract
The drug delivery approach in bone tissue engineering faces unique challenges due to the complex anatomy of bone and the limitations of drug delivery. In response, new pH-responsive nanocomposites, including magnetite nanoparticles (Fe3O4), Mobil Composition No. 41 (MCM-41), hydroxyapatite (HAP), 3-aminopropyltriethoxysilane (APTES), carboxymethyl cellulose (CMC), and montmorillonite (MMT) [(Fe3O4@MCM-41/HAP/APTES)] and hydrogel [(CMC/MMT/HAP)], have been developed for accurate delivery of teriparatide (PTH (1-34)) with the aim of increasing solubility, drug stability, and controlled release. These nanocomposites provide an efficient injectable dosing regimen that eliminates the side effects, safety concerns, and discomfort associated with repeated injections. Nanocomposites were characterized by various analytical techniques, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), zeta potential analysis, dynamic light scattering (DLS), and field emission scanning electron microscopy (FE-SEM). The average crystal diameter of the nanocomposites was calculated as 27.6 ± 4 and 29.2 ± 1.4 nm, respectively, from Scherer's equation, and the drug-loaded nanocarriers had a hydrodynamic diameter of 417.023 ± 8.3 and 193.48 ± 3.8 nm, respectively, and a stable surface charge of -31 and -40 mV, respectively. In addition, the efficiency of loading and entrapment was determined to be 37% and 90% for the first nanocomposite and 38% and 82% for the second nanocomposite, respectively. Drug release experiments using the dialysis method combined with high-performance liquid chromatography (HPLC) analysis showed a sustained release pattern. As pH decreased from 7.4 to 5.6, there was a corresponding increase in drug release. The results of the study of drug release kinetics followed the Higuchi model, which fully corresponded to the characteristics of the release target of the nanocarriers and teriparatide drug, and confirmed the preservation of the integrity of the nanocarrier. The results of the cytotoxicity test within 24 hours on the NIH3T3 cell line not only showed no toxicity but also recorded the effect of cell proliferation and differentiation, which was controlled and limited in the case of the Saos-2 cell line. Based on these findings, nanocomposites designed and manufactured with the greatest impact of components in bone tissue regeneration, as a drug delivery system, provide a very efficient approach to increase therapeutic effectiveness and thus overcome the limitations associated with drug delivery.
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Subjects


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