Hydroxyapatite Incorporated with Fe3O4@MCM-41 Core-Shell: A Promising Nanocomposite for Teriparatide Delivery in Bone Tissue Regeneration

Abstract

This article presents a comprehensive study of the development of a novel nanocomposite comprising core-shell Fe₃O₄@MCM-41 with superparamagnetic properties and hydroxyapatite (HAp). The nanocomposite serves as a pH-responsive nanocarrier, offering an efficient injectable dosage for teriparatide (PTH (1-34)) delivery. The aim is to address the limitations associated with drug-induced side effects, precautionary measures, and frequent injections. The nanocomposites, as prepared, were characterized using techniques including X-ray diffraction, Fourier transform infrared, zeta potential, dynamic light scattering, VSM, scanning electron microscopy, and transmission electron microscopy. The nanocomposites' average crystallite diameter was determined to be 27 ± 5 nm. The hydrodynamic size of the PTH (1-34)-loaded nanocarrier ranged from 357 to 495 nm, with a surface charge of -33 mV. The entrapment and loading efficiencies were determined to be 73% and 31%, respectively. All of these findings collectively affirm successful fabrication. Additionally, in vivo medication delivery was investigated using the HPLC method, mirroring the in vitro tests. Utilizing the dialysis approach, we demonstrated sustained-release behavior. PTH (1-34) diffusion increased as the pH decreased from 7.4 to 5.6. After 24 h, drug release was higher at acidic pH (88%) compared to normal pH (43%). The biocompatibility of the PTH (1-34)-loaded nanocarrier was assessed using the MTT assay employing the NIH3T3 and HEK-293 cell lines. The results demonstrated that the nanocarrier not only exhibited nontoxicity but also promoted cell proliferation and differentiation. In the in vivo test, the drug concentration reached 505 μg within 30 min of exposure to the magnetic field. Based on these findings, the Fe₃O₄@MCM-41/HAp/PTH (1-34) nanocomposite, in combination with a magnetic field, offers an efficient and biocompatible approach to enhance the therapeutic effect of osteogenesis and overcome drug limitations.

Figure 1

FT-IR spectra of Fe₃O₄ NPs, Fe₃O₄@MCM-41, HAp, Fe₃O₄@MCM-41/HAp, and Fe₃O₄@MCM-41/HAp/PTH (1–34) nanocarriers, showing the range of chemical bonds.

Figure 2

(a); XRD patterns, qualitative and quantitative analysis of Fe₃O₄, Fe₃O₄@MCM-41, HAp, (b); X-ray diffraction patterns of MCM-41, Fe₃O₄@MCM-41/HAp, and Fe₃O₄@MCM-41/HAp/PTH (1–34) nanocarriers.

Figure 3

VSM hysteresis of Fe₃O₄, Fe₃O₄@MCM-41, Fe₃O₄@MCM-41/HAp, and Fe₃O₄@MCM-41/HAp/PTH (1–34) nanocarriers.

Figure 4

SEM and TEM images of the Fe₃O₄@MCM-41/HAp/PTH (1–34) nanocarrier and its size distribution: (a,b) 30 and 50 μm scalebar, respectively, related to SEM images and (c,d) 30 and 50 nm scalebar, respectively, related to TEM images.

Figure 5

(a) Zeta potential and (b) the particle size distribution of Fe₃O₄ NPs, Fe₃O₄@MCM-41, Fe₃O₄@MCM-41/HAp, Fe₃O₄@MCM-41/HAp/PTH (1–34) nanocarriers.

Figure 6

Drug release pattern from the PTH (1–34)-loaded nanocomposite at pH levels of 5.6 and 7.4.

Figure 7

MTT assay and cytotoxicity analysis of free PTH (1–34) and 4 sample nanocarriers (compared with control cells) used; (a) NIH3T3 cell line and (b) HEK-293 cell line