Preparation and In Vitro Sustained Release Performance of Thermosensitive Gel Microsphere Composite Loaded with Anti-Tuberculosis Drug PaMZ/BMP-2

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Abstract

Objective To meet the needs of local treatment for spinal tuberculosis, this study developed a thermosensitive gel microsphere composite with both anti-tuberculosis and osteogenesis-promoting functions for efficient drug sustained release. The composite consists of anti-tuberculosis drugs (Pretomanid, Pa-824; Moxifloxacin, M; Pyrazinamide, Z) and bone morphogenetic protein-2 (BMP-2) to optimize drug release kinetics and enhance local therapeutic effects. Methods PaMZ/BMP-2 microspheres were prepared using microfluidics and characterized by SEM, particle size analysis, and XRD. LC-MS and ELISA measured drug and BMP-2 release. The thermosensitive gel (P407/P188) ratio was optimized to ensure it remained liquid at room temperature and formed a gel at 37°C for sustained release. Results Microspheres were spherical with an average size of 203.92 ± 27.76 µm. Encapsulation rates were 112.69%, 24.15%, and 15.18% for Pa, M, and Z, respectively. In vitro release showed Pa and M sustained release for over 17 days, with the gel prolonging drug release. Conclusion This study successfully prepared PaMZ/BMP-2 microspheres with good morphology and drug loading capacity, achieving controlled sustained release through thermosensitive gel. This provides a new strategy for local minimally invasive treatment of spinal tuberculosis and lays the foundation for subsequent in vivo experiments and clinical translation.

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