Development and characterization of dual drug loaded magnetic gold nanohybrid system for osteoarthritis

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.