Development, characterization, and therapeutic evaluation of uniform dezocine-loaded PLGA microspheres for sustained analgesia and cognitive protection

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OBJECTIVES: This study aimed to develop polylactic-co-glycolic acid (PLGA) microspheres encapsulating dezocine and evaluate their efficacy in managing postoperative pain and mitigating cognitive impairment. METHODS: Dezocine-loaded PLGA microspheres (DEZ@PLGA MS) were fabricated using a single-emulsion solvent evaporation technique and were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and in vitro release studies. A rat model of open reduction and internal fixation for right hindlimb tibial plateau fracture was established in healthy male rats. Following modeling, rats were randomly divided into four groups (n = 6 per group) and received intramuscular injections of equal volumes of normal saline, blank PLGA microsphere suspension, dezocine injection (5 mg/kg), or DEZ@PLGA MS suspension (5 mg/kg). Pain thresholds of the left hind paw and cognitive behavioral tests were assessed at specified time points post-administration. After testing, rats were euthanized. Muscle tissue at the injection site was collected for hematoxylin and eosin (H&E) staining to assess inflammatory responses, and hippocampal tissue was harvested for Western blot analysis. KEY FINDINGS: The SEM results revealed spherical microspheres with a smooth surface and uniform particle size. FTIR and DSC analyses confirmed stable encapsulation of dezocine (DEZ) in the PLGA matrix, with potential intermolecular interactions and amorphous drug dispersion. In vitro release studies demonstrated a sustained release profile of DEZ from the microspheres. Animal experimental results indicated that the DEZ@PLGA MS group exhibited a significantly prolonged duration of effective analgesia compared to the dezocine injection group. Additionally, DEZ@PLGA MS improved cognitive function, as evidenced by cognitive behavioral tests and Western blot results. H&E staining confirmed no significant inflammatory responses in muscle tissue across all groups, highlighting good biocompatibility of the formulation. CONCLUSIONS: Our study demonstrated that DEZ@PLGA MS effectively manages acute postoperative pain over an extended duration and improves postoperative cognitive function.

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