Wound pH-Responsive Sustained Release of Therapeutics from a Poly(NIPAAm-co-AAc) Hydrogel
Wound pH-Responsive Sustained Release of Therapeutics from a Poly(NIPAAm-co-AAc) Hydrogel
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DOI：
10.1163/092050610x545049
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Maiti, Tapas K.
中科院分区：
文献类型：
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作者：
Banerjee, Indranil;Mishra, Debasish;Maiti, Tapas K.
伤口pH值对伤口愈合过程中各种生长因子的停留时间和活性有很大影响。因此，一个ph响应的缓释生长因子递送系统可能有利于伤口的有效治疗。在这种情况下，我们试图评估聚（n -异丙基丙烯酰胺-共丙烯酸）水凝胶作为ph敏感缓释系统的潜力，用于伤口ph依赖性治疗药物的递送。采用自由基共聚法合成了该聚合物，并考察了pH对低临界溶液温度（LCST）、微结构和水凝胶溶胀的影响。结果显示，在伤口pH范围内，水凝胶的物理性质随pH值的变化而变化。光漂白后的荧光恢复（FRAP）分析证实了水凝胶中BSA的pH依赖性限制扩散。在创面pH范围（pH 6.7 ~ 7.9）内检测水凝胶中牛血清白蛋白（BSA）、血管内皮生长因子（VEGF）和表皮生长因子（EGF）的释放量（各5%，w/v）。分析显示，水凝胶的非菲克式释放，随着ph值的增加，释放速率和累积释放量发生显著变化。通过体外小鼠真皮成纤维细胞增殖研究，证实了释放的EGF保留生物活性。最后，将一种生长因子（EGF或VEGF）负载的水凝胶应用于小鼠切除伤口模型，与传统的缓释生长因子治疗相比，显示出伤口愈合的增强。(C)，莱顿，2012
Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel within the range of wound pH (pH 6.7-7.9) were examined. Analysis showed non-Fickian release of therapeutics from the hydrogel with a significant variation in release rate and cumulative release with the increase in pH. Retention of the bioactivity of the released EGF was confirmed by studying murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor (EGF or VEGF)-loaded hydrogel was applied on a murine excisional wound model and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy. (C) Koninklijke Brill NV, Leiden, 2012