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采用温敏凝胶的原位给药系统是理想的长效给药系统。该文从凝胶材料和给药系统的制备、凝胶的机体反应和体内降解以及药物控释三方面,综述了该给药系统的研究进展,总结了关键技术和科学问题,分析了面临的挑战与解决途径。水凝胶网络的不规则形态和较低的机械强度,其植入后引起的机体炎性反应、组织融合与水分快速流失及这些反应造成的凝胶网络结构和降解速率的个体差异性变化,是控制药物释放的主要困难。通过提高凝胶表面亲水性,降低其表面正电荷,或在其表面修饰抗炎性多肽,可减轻炎性作用、减缓组织融合;通过与亲水性高分子形成共混凝胶或互穿凝胶网络以及共价交联等方式,可提高凝胶强度,保持凝胶网络的空间结构和水分;通过在凝胶表面建立扩散屏障、加强药物和凝胶骨架的相互作用、构建微粒/原位凝胶复合释药系统等技术,可进一步改善药物释放特征。
In situ delivery systems using thermo-sensitive gels are ideal long-acting drug delivery systems. This article reviewed the research progress of the drug delivery system, summarized the key technologies and scientific issues, and analyzed the problems faced in the preparation of gel materials and drug delivery system, the body reaction and in vivo degradation of gel and the controlled release of drugs Challenges and solutions. The irregular morphology and low mechanical strength of the hydrogel network, the inflammatory response induced by the implants, the tissue fusion and the rapid loss of moisture and the individual differences of the gel network structure and degradation rate caused by these reactions, Is the main difficulty in controlling drug release. By increasing the hydrophilicity of the gel surface, reducing the positive charge on the surface or modifying the anti-inflammatory polypeptide on the surface of the gel, the inflammatory effect can be alleviated and the tissue fusion can be slowed down. By forming the mixed gel with the hydrophilic polymer or the interpenetrating Gel network and covalent cross-linking, etc., can improve the gel strength, maintain the spatial structure of the gel network and water; through the establishment of a diffusion barrier in the gel surface, to strengthen the drug and gel skeleton interaction, the construction of particles / Bit gel compound release system and other technologies to further improve the drug release characteristics.