Nano-carrier mediated co-delivery of methyl prednisolone and minocycline for improved post-traumatic spinal cord injury conditions in rats

Objective: The objective of this study is to investigate the fate of albumin coupled nanoparticulate system over non-targeted drug carrier in the treatment of hemisectioned spinal cord injury (SCI).

Significance: Targeted delivery of methyl prednisolone (MP) and minocycline (MC) portrayed improved therapeutic efficacy as compared with non-targeted nanoparticles (NPS).

Methods: Albumin coupled, chitosan stabilized, and cationic NPS (albumin-MP?+?MC???NPS) of poly-(lactide-co-glycolic acid) were prepared using the emulsion solvent evaporation method. Prepared NPS were characterized for drug entrapment efficiency, particle size, poly-dispersity index (PDI), zeta potential, and morphological characteristics. Their evaluation was done based on the pharmaceutical, toxicological, and pharmacological parameters.

Results and discussion: In vitro release of MP?+?MC from albumin-MP?+?MC???NPS and MP?+?MC???NPS was observed to be very controlled for the period of eight days. Cell viability study portrayed non-toxic nature of the developed NPS. Albumin-MP?+?MC???NPS showed prominent anti-inflammatory potential as compared with non-targeted NPS (MP?+?MC???NPS) when studied in LPS-induced inflamed astrocytes. Albumin-MP?+?MC???NPS reduced lesional volume and improved behavioral outcomes significantly in rats with SCI (hemisectioned injury model) when compared with that of MP?+?MC???NPS.

Conclusions: Albumin-coupled NPS carrier offered an effective method of SCI treatment following safe co-administration of MP and MC. The in vitro and in vivo effectiveness of MP?+?MC was improved tremendously when compared with the effectiveness showed by MP?+?MC???NPS. That could be attributed to the site specific, controlled release of MP?+?MC to the inflammatory site.