2. Academic Validation
  3. Porous PLGA microspheres loaded with PTH1-34 peptide for long-term treatment of OA

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

  • J Orthop Translat. 2025 Jun 9:53:99-111. doi: 10.1016/j.jot.2025.05.003.
Wang Diaodiao 1 2 3,  Tang Miaotian 4,  Ren Pengcheng 1 2 3,  Tian Zhuang 1,  Zhang Gang 1 2,  Liu Yubo 3 5,  Sun Yuyang 6,  Ye Peng 3 7,  Sun Wenqiang 3,  Yao Qi 1 2
Affiliations

Affiliations

  • 1 Department of Joint Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
  • 2 Capital Medical University, Beijing, 100069, China.
  • 3 State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100190, China.
  • 4 Department of Orthopaedics and Trauma, Peking University People's Hospital, Beijing, 100044, China.
  • 5 School of Medicine, Nankai University, Tianjin, 300071, China.
  • 6 Department of Anesthesiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100005, China.
  • 7 Beijing Key Laboratory of Lignocellulosic Chemistry College of Material Science and Technology, Beijing Forestry University, Beijing, 100083, China.
PMID: 40538640 DOI: 10.1016/j.jot.2025.05.003
Abstract

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 (PTH1-34) 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@PTH1-34) were fabricated using FDA-approved poly (lactic-co-glycolic acid) (PLGA) as the matrix, encapsulating PTH1-34 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: PTH1-34 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@PTH1-34 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@PTH1-34 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@PTH1-34) that enables continuous drug release for over 30 days following single intra-articular administration. M@PTH1-34 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.

Keywords

Cartilage repair; Osteoarthritis; PTH1-34; Porous PLGA microspheres; Sustained release.

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