An In Situ Gelling Drug Delivery System for Improved Recovery after Spinal Cord Injury
An In Situ Gelling Drug Delivery System for Improved Recovery after Spinal Cord Injury
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用于改善脊髓损伤后恢复的原位凝胶药物输送系统
DOI：
10.1002/adhm.201600055
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发表时间：
2016-06-22
影响因子：
10
通讯作者：
Fan, Jin
中科院分区：
文献类型：
--
作者：
Liu, Dongfei;Jiang, Tao;Fan, Jin
脊髓损伤（SCI）的治疗策略受到现有药物输送技术的限制。在这里，原位胶凝药物递送系统（DDS），由泊洛沙姆-407，188混合物为基础的温敏水凝胶基质，并纳入治疗化合物（单唾液酸神经节苷脂，GM 1），被开发用于SCI治疗。采用大鼠下胸半横断脊髓损伤模型评价治疗效果。由于温度升高，掺入GM 1的泊洛沙姆-407和188聚合物溶液在滴注到损伤的脊髓后转化为水凝胶（GM 1-水凝胶）。在体温下，由于水凝胶基质的溶解和溶胀（异常转运）的叠加，温度响应性水凝胶抑制GM 1的释放约1个月。GM 1-水凝胶的持续释放能够延长GM 1在受损脊髓处的停留时间，降低给药频率，因此可以改善患者的依从性。脊髓损伤后，GM 1-水凝胶可抑制细胞凋亡和胶质瘢痕形成，促进神经元再生，对损伤脊髓提供神经保护，改善运动功能恢复。总体而言，这项研究开辟了未来的前景，为SCI的治疗与延长药物释放DDS。
Therapeutic strategies for the spinal cord injury (SCI) are limited by the current available drug delivery techniques. Here, an in situ gelling drug delivery system (DDS), composed of a Poloxamer-407, a 188 mixture-based thermoresponsive hydrogel matrix and, an incorporated therapeutic compound (monosialoganglioside, GM1), is developed for SCI therapy. A low-thoracic hemisection in rats is used as SCI model to evaluate therapeutic efficiency. The GM1-incorporating Poloxamer-407 and 188 polymer solution is converted to a hydrogel (GM1-hydrogel) upon instillation to the injured spinal cord, due to the increased temperature. At body temperature, the thermoresponsive hydrogel prolongs the release of GM1 for about 1 month, due to the superposition of dissolution and swelling (anomalous transport) of the hydrogel matrix. The sustained release of the GM1-hydrogel enables the prolonged residence time of GM1 at the injured spinal cord, decreases the frequency of administration and, consequently, may improve patient compliance. After SCI, the administration of GM1-hydrogel to the lesion site inhibits the apoptotic cell death and glial scar formation, enhances the neuron regeneration, provides neuroprotection to the injured spinal cord, and improves the locomotor recovery. Overall, this study opens future perspectives for the treatment of SCI with a prolonged drug release DDS.