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

Abstract

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.

Keywords:

• Spinal cord injury
• albumin-coupled nanoparticle
• methyl prednisolone
• minocycline
• PLGA

Acknowledgements

The authors are obliged to Shanghai General Hospital, Shanghai Jiao Tong University, China, for providing research facilities.

Disclosure statement

The authors declare that there is no conflict of interests regarding the publication of this paper.

Additional information

Funding

This work was supported by Pudong Health Bureau of Shanghai in the form of Key Discipline Construction Project [grant number PWZx2014-02].