Versatile injectable supramolecular hydrogels containing drug loaded micelles for delivery of various drugs
Versatile injectable supramolecular hydrogels containing drug loaded micelles for delivery of various drugs
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含有载药胶束的多功能可注射超分子水凝胶，用于输送各种药物
DOI：
10.1039/c3py01083j
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发表时间：
2014-02-07
影响因子：
4.6
通讯作者：
Yao, Ping
中科院分区：
文献类型：
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作者：
Liu, Zhijia;Yao, Ping
在本研究中，通过在Pluronic F127的末端添加羧基，然后在羧基化的Pluronic F127与乙二醇壳聚糖之间进行酰胺化反应，制备新型乙二醇壳聚糖-Pluronic F127缀合物（GC-PF 127）。由于PPO链段在Pluronic F127中的疏水聚集，GC-PF 127在室温下在水溶液中自组装成胶束。该胶束在中性pH下可以以不同的机制有效负载两亲性阿霉素（DOX）和部分负载带负电荷的蛋白质超氧化物歧化酶（SOD），但不能负载亲水性5-氟尿嘧啶（5-FU）。加入α-CD可将DOX/GC-PF 127、SOD/GC-PF 127和5-FU/GC-PF 127胶束溶液分别转化为可注射的超分子水凝胶。水凝胶的强度和解离速率可以通过α-CD浓度来调节。水凝胶结构可以在使用注射器挤出水凝胶后立即恢复。水凝胶对各种药物具有延长的和几乎线性的释放行为。水凝胶在生理条件下通过水凝胶的解离释放游离药物以及载药胶束，这可以增强靶向能力和治疗效率。释放的胶束依次释放游离药物，进一步延长药物的释放。GC-PF 127水凝胶是一种多用途的可注射水凝胶，可递送各种药物。
In this study, a novel glycol chitosan-Pluronic F127 conjugate (GC-PF127) was produced by adding a carboxyl group to the end of Pluronic F127 followed by an amidation reaction between carboxylated Pluronic F127 and glycol chitosan. Because of the hydrophobic aggregation of PPO segments in Pluronic F127, GC-PF127 self-assembles into micelles in aqueous solution at room temperature. The micelles can effectively load amphiphilic doxorubicin (DOX) and partly load negatively charged protein superoxide dismutase (SOD) at neutral pH with different mechanisms, but cannot load hydrophilic 5-fluorouracil (5-FU). The respective DOX/GC-PF127, SOD/GC-PF127, and 5-FU/GC-PF127 micelle solutions can be converted to injectable supramolecular hydrogels by addition of α-CD. The strength and dissociation rate of the hydrogels can be tuned by the α-CD concentration. The hydrogel structure can recover immediately after extrusion of the hydrogel using a syringe. The hydrogels have prolonged and almost linear release behaviours for various drugs. The hydrogels release free drugs as well as drug loaded micelles via the dissociation of the hydrogels under physiological conditions, which may enhance the targeting ability and therapeutic efficiency. The released micelles sequentially release free drugs that further prolong the release of the drugs. GC-PF127 hydrogels are versatile injectable hydrogels which can deliver various drugs.