Porous PLGA microspheres loaded with PTH1-34 peptide for long-term treatment of OA

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Background Osteoarthritis (OA) is a chronic disease characterized by degeneration of articular cartilage, affecting over 530 million patients worldwide. Current oral medications such as non-steroidal anti-inflammatory drugs (NSAIDs) can only alleviate symptoms and are associated with numerous adverse effects. Although teriparatide (PTH 1-34 ) exhibits dual functions of chondroprotection and osteogenic effects, its clinical application is significantly limited by its short biological half-life (30–60 min) and accelerated degradation within the inflammatory microenvironment of joint cavities. Methods Porous sustained-release microspheres (M@PTH 1-34 ) were fabricated using FDA-approved poly (lactic-co-glycolic acid) (PLGA) as the matrix, encapsulating PTH 1-34 within their multi-channel porous structure. Uniform microsphere preparation and high-efficiency drug loading were achieved through membrane emulsification and temperature-controlled embedding techniques. To systematically evaluate the sustained-release profile and therapeutic outcomes, both in vitro and in vivo OA models were established, enabling comprehensive analysis of cartilage repair efficacy, anti-inflammatory regulation, and immunomodulatory effects. Results PTH 1-34 could be efficiently loaded into microspheres after self-healing and achieve consistent release over 30 days with biological activity being maintained. In OA model rats, M@PTH 1-34 significantly improved behavioral and radiological outcomes, increased cartilage smoothness and thickness, and increased the expression of chondrogenic markers. Additionally, in vitro and in vivo safety tests revealed no significant safety issues. These findings indicate that M@PTH 1-34 holds promise as a long-lasting, cost-effective, and safe therapeutic approach for OA. Conclusion This study successfully developed a uniform-sized PLGA-based sustained-release microsphere system (M@PTH 1-34 ) that enables continuous drug release for over 30 days following single intra-articular administration. M@PTH 1-34 exerts its therapeutic effects on osteoarthritis through the following two ways: (1) Promoting cartilage repair by enhancing the chondrogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs); (2) Improve the inflammatory microenvironment of joints by inhibiting the expression of inflammatory factors (such as IL-1β) and regulating the polarization state of M1/M2 macrophages. The translation potential of this article The system demonstrates prominent clinical translation advantages: (1) Innovative utilization of FDA-approved PLGA carrier combined with membrane emulsification technique ensures precise size control and standardized production; (2) Localized delivery strategy achieves targeted retention within articular cavity, validated by animal studies showing no systemic exposure risks; (3) Standardized preparation process demonstrates the feasibility of industrial-scale production.

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