Controllable preparation of SB-3CT loaded PLGA microcapsules for traumatic-brain-injury pharmaco-therapy

This study is to explore controllable preparation of poly (lactic-co-glycolic acid) (PLGA) microcapsules to load 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT) for traumatic brain injury (TBI) pharmacological therapy. Capillary-based microfluidic method was proposed to prepare SB-3CT loaded PLGA microcapsules. Drug loading and release behavior of the corresponding PLGA microcapsules were evaluated and correlated with their degradation profile. The obtained PLGA microcapsules had a golf-featured morphology and high mono-dispersion. Precise control on the size and size distribution of the microcapsules could be achieved by varying the geometry of the capillary device and operation parameters to yield uniform and reproducible PLGA microcapsules in the range of 35-65 µm. A high drug encapsulation efficiency of 99% within the obtained PLGA microcapsules with a releasing duration of around 50 d was ensured. Pharmacological therapy of TBI was tried by local injection of PLGA-SB-3CT suspension in rats at the trauma site after TBI. The protection on brain tissue upon administration was demonstrated by accelerated behavioral recovery (beam balance and beam walk latencies, and spatial memory ability) and reduction in the neuronal cell apoptosis in CA2 and hilus hippocampus as well as the injury cortical region. Hence, PLGA-SB-3CT could serve as a promising pharmaco-therapeutic option for TBI treatment.