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.