Dextran-based biodegradable nanoparticles: an alternative and convenient strategy for treatment of traumatic spinal cord injury.

Abstract

IntroductionAfter traumatic spinal cord injury (SCI), an inhibitory environment that contains chondroitin sulfate proteoglycans (CSPGs) is formed that prevents axonal regeneration and growth.Materials and methodsAs previously reported, local administration of Taxol® at a low concentration has shown promising abilities to promote axonal regeneration and downregulate inhibitory molecules after acute SCI. However, the application of an invasive miniosmotic pump to deliver Taxol and the Cremophor-related toxicity caused by Taxol limits the administration of Taxol.ResultsIn this study, the sustained release of paclitaxel (PTX) for 7 days was achieved by incorporating PTX into acetalated dextran (Ac-DEX) nanoparticles, and the prepared PTX-loaded Ac-DEX (PTX@Ac-DEX) nanoparticles promoted neurite extension in the presence of CSPGs. In a rat SCI model, both PTX@Ac-DEX and Taxol enhanced neural regeneration, inhibited CSPGs, protected the injured spinal cord, and improved locomotor recovery. Because of the sustained release of PTX, single administration of PTX@Ac-DEX showed equal therapeutic effect with Taxol, which need to be administered for seven days using a surgically implanted miniosmotic pump.ConclusionOverall, this study provides an effective and convenient strategy for SCI therapy, which can improve neurite extension across an inhibitory environment and avoid Cremophor-related toxicity caused by Taxol.