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Dual Regulations of Thermosensitive Heparin–Poloxamer Hydrogel Using ε-Polylysine: Bioadhesivity and Controlled KGF Release for Enhancing Wound Healing of Endometrial Injury

自愈水凝胶 黏膜黏附 角质形成细胞生长因子 泊洛沙姆 材料科学 伤口愈合 粘附 药理学 生物医学工程 生长因子 药物输送 毒品携带者 医学 聚合物 外科 内科学 复合材料 纳米技术 高分子化学 受体 共聚物
作者
He‐Lin Xu,Jie Xu,Bi‐Xin Shen,Si‐Si Zhang,Bing‐Hui Jin,Qunyan Zhu,De‐Li ZhuGe,Xueqing Wu,Jian Xiao,Ying‐Zheng Zhao
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:9 (35): 29580-29594 被引量:63
标识
DOI:10.1021/acsami.7b10211
摘要

Hydrogel was not only used as an effective support matrix to prevent intrauterine adhesion after endometrial injury but also served as scaffold to sustain release of some therapeutics, especially growth factor. However, because of the rapid turnover of the endometrial mucus, the poor retention and bad absorption of therapeutic agents in damaged endometrial cavity were two important factors hindering their pharmacologic effect. Herein, a mucoadhesive hydrogel was described by using heparin-modified poloxamer (HP) as the matrix material and ε-polylysine (EPL) as functional excipient. Various EPL-HP hydrogels formulations are screened by rheological evaluation and mucoadhesion studies. It was found that the rheological and mucoadhesive properties of EPL-HP hydrogels were easily controlled by changing the amount of EPL in formulation. The storage modulus of EPL-HP hydrogel with 90 μg/mL of EPL (EPL-HP-90) was elevated to be 1.9 × 105 Pa, in accordance with the adhesion force rising to 3.18 N (10-fold higher than HP hydrogels). Moreover, in vitro release of model drug keratinocyte growth factor (KGF) from EPL-HP hydrogel was significantly accelerated by adding EPL in comparison with HP hydrogel. Both strong mucoadhesive ability and the accelerated drug release behavior for EPL-HP-90 made more of the encapsulated KGF absorbed by the uterus basal layer and endometrial glands after 8 h of administration in uterus cavity. Meanwhile, the morphology of endometrium in the injured uterus was repaired well after 3 d of treatment with KGF-EPL-HP-90 hydrogels. Compared with KGF-HP group, not only proliferation of endometrial epithelial cell and glands but also angiogenesis in the regenerated endometrium was obviously enhanced after treatment with KGF-EPL-HP-90 hydrogels. Alternatively, the cellular apoptosis in the damaged endometrium was significantly inhibited after treatment with KGF-EPL-HP-90 hydrogels. Overall, the mucoadhesive EPL-HP hydrogel with a suitable KGF release profile may be a more promising approach than HP hydrogel alone to repair the injured endometrium.
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