Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials.

Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials.
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DOI:
10.1016/j.biomaterials.2010.09.053
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发表时间:
2011-01
期刊:
影响因子:
14
通讯作者:
Chen, Weiliam
Chen, Weiliam
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhang, Hanwei;Qadeer, Aisha;Mynarcik, Dennis;Chen, Weiliam

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一种原位可胶凝和生物可降解的三重互穿网络(3XN)水凝胶,完全不含潜在的细胞毒性外来小分子交联剂,由部分氧化的葡聚糖(Odex),硬骨鱼和N-羧乙基壳聚糖(CEC)配制。3XN水凝胶的流变学特征和机械强度都接近由二元部分制剂组成的三种单独水凝胶的组合特征(即,Odex/CEC、Odex/硬骨鱼和CEC/硬骨鱼)。与细胞培养模型中的每种部分制剂相比,3XN水凝胶对成纤维细胞介导的降解具有显著更高的抗性;这归因于互穿的三重网络结构。3XN水凝胶中硬骨鱼聚糖的存在赋予细胞亲和力,构成适合成纤维细胞生长的环境。体内皮下注射到小鼠模型中显示,3XN水凝胶不诱导广泛的炎症反应,也没有任何组织坏死的证据,进一步证实了水凝胶及其降解副产物的非细胞毒性。重要的是,使用罗格列酮作为模型药物证实了3XN水凝胶作为持续药物递送载体的能力。罗格列酮的存在深刻地改变了细胞/组织与皮下注射的3XN水凝胶的相互作用。罗格列酮以剂量依赖性方式抑制炎症反应和组织修复,并显著减缓水凝胶降解。
An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e., Odex/CEC, Odex/teleostean, and CEC/teleostean). The 3XN hydrogel is considerably more resistant to fibroblast-mediated degradation compare to each partial formulation in cell culture models; this is attributable to the interpenetrating triple network structure. The presence of teleostean in the 3XN hydrogel imparts cell affinity, constituting an environment amenable to fibroblast growth. in vivo subdermal injection into mouse model shows that the 3XN hydrogel does not induce extensive inflammatory response nor is there any evidence of tissue necrosis, further confirming the non-cytotoxicity of the hydrogel and its degradation byproducts. Importantly, the capability of the 3XN hydrogel to serve as a sustained drug delivery vehicle is confirmed using rosiglitazone as a model drug. The presence of rosiglitazone profoundly changes the cell/tissue interactions with the subdermally injected 3XN hydrogel. Rosiglitazone suppresses both the inflammatory response and tissue repair in a dose-dependent manner and considerably moderated the hydrogel degradation.
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