Rehman Gul, Khan Jadoon, Alrashed May M, Abbas Muhammad, Rehman Masood Ur, Shah Tawaf Ali, Attia Kotb A, Mohammed Arif Ahmed
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Department of Pharmacy, IQRA University Chak Shahzad Campus, Islamabad, Pakistan.
J Biomater Appl. 2025 May;39(10):1222-1239. doi: 10.1177/08853282251324352. Epub 2025 Mar 3.
Cartilage deterioration in patients with osteoarthritis presents a significant challenge, primarily attributable to the inadequate oral bioavailability and poor dosage compliance of chondroprotective agents. The Chondroitin Sulphate (CS) is a stabilizing and reducing agent for metal NP as well as homing agent by binding to surface molecules (CD44, L-selectin, P-selectin, and annexin-6) of chondrocytes at the OA site. This study was designed to develop intra-articular magnetic gold nanohybrids for the co-delivery of chondroitin sulfate, glucosamine sulfate, and gold, aiming to achieve synergistic anti-inflammatory and cartilage regenerative effects and in vitro assessments of drug release were conducted. Additionally, in animal study, the male albino rats underwent anesthesia by inhaling isoflurane using the open-drop exposure method, and chondrocytes were then harvested for cytotoxicity and biocompatibility assays. Physical characterization revealed 66 nm particle size with uniform distribution and colloidal stability of MGN-CS-GS. Zeta potential and FTIR analysis showed electrostatic interaction between the carboxyl and amino groups of MGN-CS and GS. VSM and EDX confirmed paramagnetic and core-shell characteristics of nanohybrids, respectively. It was found that the MGN-CS-GS released more CS (72%) and GS (85%) at acidic pH with continuous release pattern, which will improve patient compliance. The nanohybrid's cytotoxicity assay demonstrated excellent biocompatibility and cellular viability of OA chondrocytes triggered by interleukin-1β (IL-1β) compared to marketed formulation. The results demonstrated that MGN-CS-GS continuously released both drugs with high biocompatibility and cellular viability of OA chondrocytes. The successful synthesis of MGN-CS-GS is a foundation for further research on its potential application as a novel co-drug carrier nanohybrid system.
骨关节炎患者的软骨退化是一项重大挑战，主要归因于软骨保护剂口服生物利用度不足和剂量依从性差。硫酸软骨素（CS）是金属纳米颗粒的稳定剂和还原剂，也是通过与骨关节炎部位软骨细胞的表面分子（CD44、L-选择素、P-选择素和膜联蛋白-6）结合的归巢剂。本研究旨在开发用于共递送硫酸软骨素、硫酸氨基葡萄糖和金的关节内磁性金纳米杂化物，以实现协同抗炎和软骨再生效果，并进行了药物释放的体外评估。此外，在动物研究中，雄性白化大鼠采用开放式滴注暴露法吸入异氟烷进行麻醉，然后收集软骨细胞进行细胞毒性和生物相容性测定。物理表征显示MGN-CS-GS的粒径为66nm，分布均匀且具有胶体稳定性。zeta电位和傅里叶变换红外光谱分析表明MGN-CS和GS的羧基和氨基之间存在静电相互作用。振动样品磁强计和能量色散X射线光谱分别证实了纳米杂化物的顺磁性和核壳特征。结果发现，MGN-CS-GS在酸性pH下以持续释放模式释放更多的CS（72%）和GS（85%），这将提高患者的依从性。与市售制剂相比，纳米杂化物的细胞毒性测定表明，白细胞介素-1β（IL-1β）触发的骨关节炎软骨细胞具有优异的生物相容性和细胞活力。结果表明，MGN-CS-GS持续释放两种药物，对骨关节炎软骨细胞具有高生物相容性和细胞活力。MGN-CS-GS的成功合成是进一步研究其作为新型共药物载体纳米杂化物系统潜在应用的基础。
