Treating acute spinal cord injury with methylprednisolone modified and loaded glycol chitosan nanocarriers

Jacqueline Yvonne Tyler, Purdue University

Abstract

Methylprednisolone (MP), which is the only drug used clinically for acute spinal cord injury treatment, remains controversial; the high dosage required to achieve therapeutic levels of the drug causes systemic toxicity. We address this challenge by improving the bioavailability of MP at the injury site, allowing a lower dosage, and consequently reducing the toxicity associated with treatment. To accomplish this goal, nanocarriers were formulated from a glycol chitosan backbone modified with MP (termed as GC-MP). The nanocarrier can be loaded with 15% by weight free MP (termed as GC-MP/MP). Importantly, the conjugated MP can be gradually released from the GC backbone via cleavage of the ester bond. Thus our system allows both burst and extended delivery of MP to the injury site. Pharmacokinetic studies showed an initial burst release of free MP from the nanocarrier core and prolonged circulation of the GC-MP polymer. Biodistribution studies corroborate this data, demonstrating that the glycol chitosan carrier increases accumulation of MP in the spinal cord tissue. Finally, pilot locomotor functional recovery studies showed that animals treated with GC-MP/MP and GC-MP both recovered significantly greater function than animals treated with clinical dose MPHS or saline.

Degree

M.S.B.M.E.

Advisors

Cheng, Purdue University.

Subject Area

Biomedical engineering

COinS