International Journal of Nanomedicine (Jul 2018)

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

  • Liu W,
  • Quan P,
  • Li Q,
  • Tang P,
  • Chen J,
  • Jiang T,
  • Cai W

Journal volume & issue
Vol. Volume 13
pp. 4121 – 4132

Abstract

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Wei Liu,1,* Peng Quan,2,* Qingqing Li,1,* Pengyu Tang,1 Jian Chen,1 Tao Jiang,3 Weihua Cai1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; 2Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 3Department of Orthopaedics, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, China *These authors contributed equally to this work Introduction: After traumatic spinal cord injury (SCI), an inhibitory environment that contains chondroitin sulfate proteoglycans (CSPGs) is formed that prevents axonal regeneration and growth.Materials and methods: As 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.Results: In 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.Conclusion: Overall, 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. Keywords: acetalated dextran, nanoparticle, paclitaxel, spinal cord injury

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