PLGA Microparticles as a Stable and Biocompatible Carrier for Adiponectin Delivery to Enhance Bone Regeneration
Pengxin Zhang1,2,3, Yang Wang1,2, Fan Hu1,2
1Department of Endocrinology, The Second Medical Center, The Chinese People's Liberation Army General Hospital, Beijing 100853, China.
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Background: Adiponectin (ADPN) is a key adipokine with osteogenic potential, but its clinical translation for bone regeneration is hindered by poor in vivo stability. This study aimed to develop poly lactic-co-glycolic acid (PLGA) microparticles as a stable and biocompatible carrier for sustained ADPN delivery to enhance bone repair. Methods: ADPN-loaded PLGA microparticles (ADPN-MPs) were fabricated via emulsion solvent evaporation. Their physicochemical properties were characterized using scanning electron microscopy (SEM) and circular dichroism (CD) spectroscopy. Loading efficiency and drug loading were quantified. In vitro release kinetics and stability under physiological conditions were assessed. Biocompatibility was evaluated using MC3T3-E1 osteoblasts and BMSCs, and in vivo efficacy was tested in a fracture model via gait analysis. Results: Employing CD to evaluate the secondary structure of ADPN, emulsion solvent evaporation for microparticles preparation, and SEM for morphological analysis, we quantitatively assessed the loading efficiency (69.83 ± 4.24%) and drug loading (0.97 ± 0.06%) of ADPN-MPs. Results indicated that ADPN-MPs maintained significant stability under varied pH and temperature conditions and exhibited a controlled release profile, with an average initial rapid release of 14.25% within 24 h and an average cumulative release of 55.00% by day 28. Furthermore, ADPN-MPs promoted the proliferation of MC3T3-E1 and BMSCs without toxicity, demonstrating excellent biocompatibility. Notably, gait analysis in a fracture model showed improved healing in both ADPN and ADPN-MPs groups compared to controls, with ADPN-MPs demonstrating comparable efficacy to free ADPN, supporting its potential as a stable delivery system for bone regeneration. Conclusions: PLGA microparticles serve as an effective, stable, and biocompatible delivery platform for ADPN, significantly promoting bone regeneration in vitro and in vivo. This delivery system enhances the therapeutic potential of ADPN for clinical bone repair applications.
