Abstract
Drug delivery for neuroprotection/neuroregeneration after traumatic peripheral nerve injuries still remains a challenge. For this purpose, we formulated composite nanofiber formulation for the dual local delivery of alpha lipoic acid (ALA) and atorvastatin (ATR) to enhance regeneration process after peripheral nerve injury. The initial stage involved encapsulation of ATR into nanosprayed chitosan (CH) nanoparticles after which the CH nanoparticles were embedded into poly(lactic-co-glycolic acid) (PLGA) nanofibers containing freely dispersed ALA within the fiber structure. Morphology investigations revealed that smooth and randomly aligned nanofibers with mean diameter of 340±69 nm were formed. Encapsulation efficiency for ALA and ATR were calculated as 92.76±3.53 % and 89.27±5.053 %, respectively. Differential Scanning Calorimetry and FT-IR analysis confirmed successful encapsulation of ALA and ATR into the composite nanofibers; however, XRD results indicated surface localization of ALA within the structure. Porosity and pore volume of the nanofibers increased in accordance with increase in density of the electrospunned solution. Similarly, mechanical strength of the nanofibers was found to increase significantly following the incorporation of ALA and ATR with respect to the unloaded nanofibers (p<0.05). Dual release of ALA and ATR in different fashions was confirmed by in-vitro release test of the nanofibers. For ALA, an immediate release percentage of 83.90 % within the first hour was observed. On the other hand, ATR exhibited a three-stage release profile which begins with a relatively lower initial release (22.07 %) in comparison to ALA followed by an increasing release (82.439%) up to 150 h. According to cell viability results, blank and loaded formulations were found to have no cytotoxic effect on both L-929 and B35 cell lines after incubation for up to 48 h. Based on this, composite PLGA nanofibers could be classified as suitable candidates for long-term and local delivery of neuroprotective drugs in peripheral nerve injury.
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