Synergistic effects of hydroxyapatite, montmorillonite and carboxymethylcellulose in pH-responsive nanocomposites for teriparatide delivery

IF 6.5 Q1 CHEMISTRY, APPLIED

Carbohydrate Polymer Technologies and Applications Pub Date : 2025-09-24 DOI:10.1016/j.carpta.2025.101013

Hamid Reza Hosseini , Majid Abdouss , Zahra Hosseini , Mehrab Pourmadadi

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引用次数: 0

Abstract

Despite significant progress, the approach to drug delivery in bone tissue engineering encounters unique challenges due to the intricate bone anatomy. In response, a novel pH-responsive hydrogel nanocomposite (CMC/MMT/HAP) has been developed for precise delivery of Teriparatide (PTH (1-34)), with the primary objective of enhancing drug solubility, stability, and mitigating degradation. This nanocomposite provides an efficient injectable dosage regimen, addressing side effects, safety concerns, and the inconvenience of frequent injections. The nanocomposites underwent comprehensive characterization through 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 nanocomposites displayed an average crystallite diameter of 29.2 ± 1.4 nm. The PTH (1-34)-loaded nanocarrier exhibited a hydrodynamic size of 193.48 ± 3.8 nm and a surface charge of − 40 mV. Furthermore, the loading and encapsulation efficiencies were determined to be 38% and 82%, respectively. Utilizing the dialysis method in conjunction with High-Performance Liquid Chromatography (HPLC) analysis, drug diffusion experiments unveiled a sustained-release pattern. As the pH decreased from 7.4 to 5.6, there was a corresponding increase in PTH (1-34) diffusion. After 24 h, drug release was higher in the acidic pH (58%) compared to the physiological pH (32%). This trend persisted, culminating in 98.5% and 64% release percentages after 240 h. Swelling tests demonstrated that the hydrogel exhibited a high fluid absorption capacity in physiological-like conditions, a property that facilitates enhanced tissue integration and supports sustained, diffusion-controlled drug release. The alkaline phosphatase (ALP) activity assay showed a marked increase in osteogenic differentiation, with the nanocomposite exhibiting the highest activity, highlighting its potential for bone regeneration. The biocompatibility of the PTH (1-34)-loaded nanocarrier was evaluated using the MTT assay with L929, HEK-293, and SaOS-2 cell lines as test models.The results affirmed its non-toxic nature and demonstrated its ability to stimulate cell proliferation and differentiation. Drawing insights from these findings, the CMC/MMT/HAP@PTH (1-34) nanocomposite, as a drug delivery system, presents a highly efficient and biocompatible approach to enhance therapeutic efficacy, thereby overcoming limitations associated with drug delivery.

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羟基磷灰石、蒙脱土和羧甲基纤维素在ph响应纳米复合材料中对特立帕肽的协同作用

尽管取得了重大进展，但由于复杂的骨骼解剖结构，骨组织工程中的药物递送方法面临着独特的挑战。为此，研究人员开发了一种新的ph响应水凝胶纳米复合材料（CMC/MMT/HAP），用于精确递送特立帕肽（PTH(1-34)），其主要目的是提高药物的溶解度、稳定性和减轻降解。这种纳米复合材料提供了一种有效的注射给药方案，解决了副作用、安全问题和频繁注射的不便。通过各种分析技术，包括x射线衍射（XRD），傅里叶变换红外光谱（FT-IR）， Zeta电位分析，动态光散射（DLS）和场发射扫描电镜（FE-SEM），对纳米复合材料进行了全面的表征。纳米复合材料的平均晶径为29.2±1.4 nm。负载PTH（1-34）的纳米载体的水动力尺寸为193.48±3.8 nm，表面电荷为−40 mV。此外，确定了负载和封装效率分别为38%和82%。利用透析法结合高效液相色谱（HPLC）分析，药物扩散实验揭示了一个缓释模式。随着pH值从7.4降低到5.6，PTH（1-34）的扩散相应增加。24 h后，酸性pH下的药物释放量（58%）高于生理pH（32%）。这种趋势持续下去，在240小时后达到98.5%和64%的释放率。肿胀测试表明，水凝胶在生理条件下表现出较高的液体吸收能力，这种特性有助于增强组织整合，并支持持续的扩散控制药物释放。碱性磷酸酶（ALP）活性测定显示成骨分化明显增加，纳米复合材料表现出最高的活性，突出了其骨再生的潜力。以L929、HEK-293和SaOS-2细胞系为实验模型，采用MTT法评价PTH（1-34）纳米载体的生物相容性。结果证实了其无毒性质，并证明了其刺激细胞增殖和分化的能力。根据这些发现，CMC/MMT/HAP@PTH（1-34）纳米复合材料作为一种药物传递系统，提供了一种高效和生物相容性的方法来提高治疗效果，从而克服了与药物传递相关的局限性。

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来源期刊

Carbohydrate Polymer Technologies and Applications

CiteScore

8.70

自引率

0.00%

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