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含 rhEGF 的液晶前体的原位凝胶化,具有良好的载药稳定性和体系力学性能:一种用于慢性伤口治疗的新型给药系统。

In situ gelation of rhEGF-containing liquid crystalline precursor with good cargo stability and system mechanical properties: a novel delivery system for chronic wounds treatment.

机构信息

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, P. R. China.

出版信息

Biomater Sci. 2019 Feb 26;7(3):995-1010. doi: 10.1039/c8bm01196f.

Abstract

The objective of this study was to develop a novel delivery system for recombinant human epidermal growth factor (rhEGF) for chronic wound treatment. Such a delivery system should be of good cargo stability and system mechanical properties in order to guarantee a satisfactory wound-healing effect. rhEGF-containing lyotropic liquid crystalline precursors (rhEGF-LLCPs) with in situ gelation capability were considered as a promising candidate to achieve this aim. Various properties of the optimal formulations (rhEGF-LLCP1 and rhEGF-LLCP2) were characterized, including apparent viscosity, gelation time, in vitro release and phase behavior. The stability of rhEGF and system mechanical properties (i.e. mechanical rigidity and bioadhesive force) were verified. Interestingly, rhEGF-LLCP2 with a larger internal water channel diameter exhibited faster release rate in vitro and then better bioactivity in Balb/c 3T3 and HaCaT cell models. Moreover, rhEGF-LLCP2 showed distinct promotion effects on wound closure, inflammatory recovery and re-epithelization process in Sprague-Dawley rat models. In conclusion, rhEGF-LLCP emerged as a prospective candidate to preserve the stability and enhance the wound-healing effect of rhEGF, which might serve as a new delivery system for chronic wound therapies.

摘要

本研究旨在开发一种新型的重组人表皮生长因子(rhEGF)传递系统,用于慢性伤口治疗。这种传递系统应该具有良好的货物稳定性和系统力学性能,以保证令人满意的伤口愈合效果。具有原位凝胶形成能力的含 rhEGF 的溶致液晶前体(rhEGF-LLCP)被认为是实现这一目标的有前途的候选物。对最佳配方(rhEGF-LLCP1 和 rhEGF-LLCP2)的各种性质进行了表征,包括表观粘度、凝胶时间、体外释放和相行为。验证了 rhEGF 的稳定性和系统力学性能(即机械刚性和生物粘附力)。有趣的是,具有较大内部水通道直径的 rhEGF-LLCP2 在体外表现出更快的释放速率,然后在 Balb/c 3T3 和 HaCaT 细胞模型中表现出更好的生物活性。此外,rhEGF-LLCP2 在 Sprague-Dawley 大鼠模型中对伤口闭合、炎症恢复和再上皮化过程表现出明显的促进作用。总之,rhEGF-LLCP 作为一种有前途的候选物,可以保持 rhEGF 的稳定性并增强其伤口愈合效果,有望成为慢性伤口治疗的新型传递系统。

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