温敏凝胶原位植入给药系统：进展与挑战

采用温敏凝胶的原位给药系统是理想的长效给药系统。本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轻度，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 Implant Drug Delivery Based on Thermosensitive Hydrogel: Recent Advances and Challenges

Thermosensitive hydrogels are of great potential in in situ implantation for long-term controlled drug release. The present article reviewed the recent research progress in the preparation of thermosensitive hydrogel and the drug delivery system, the body response to and the degradation of the hydrogel, as well as the drug release form the hydrogel. The challenges of implant drug delivery based on thermosensitive hydrogel were presented and the solutions were discussed. The major handicaps in controlled drug delivery of the thermosensitive hydrogel include the flexible network with high water content and low mechanical strength, inducing the body inflammatory responses and invaded by the tissue after implantation, and the individual differences in the degradation and evolution of the network. Many researches developed various approaches to overcome these handicaps. The body inflammatory responses and tissue invading can be mitigated by either improving the hydrophilicity and reducing the positive charge of the hydrogel or incorporation with the anti-inflammatory peptides. The mechanical strength might be promoted by cross-linking, blending hydrophilic polymer in to the hydrogel, or preparing the interpenetrating polymer network, so that the network and water can be maintained for longer period. Further approaches to improve the controlled drug delivery involve building drug diffusion barrier on the hydrogel surface, enhancing the interaction between the drug and the polymer in hydrogel, and the combination hydrogel with drug-loaded micro/nanoparticles.