Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada L8S 4L7.
Biomacromolecules. 2011 Nov 14;12(11):4112-20. doi: 10.1021/bm201170h. Epub 2011 Oct 24.
The design and application of soft nanocomposite injectable hydrogels containing entrapped microgels for small-molecule drug delivery is demonstrated. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited both ionic and hydrophobic affinity for binding to bupivacaine, a cationic local anesthetic used as a model drug. Microgels were subsequently immobilized within an in situ-gelling hydrogel network cross-linked via hydrazide-aldehyde chemistry to generate hydrogel-microgel soft nanocomposites. Drug release could be sustained for up to 60 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or microgels alone (<1 week). Drug release kinetics could be readily tuned by varying the affinity of the microgel and hydrogel phases for drug-polymer interactions and the network density of the hydrogel phase.
本文展示了一种含有包埋微凝胶的软纳复合可注射水凝胶的设计与应用，用于小分子药物输送。合成了基于 N-异丙基丙烯酰胺和丙烯酸的共聚微凝胶，它们对布比卡因（一种用作模型药物的阳离子局部麻醉剂）具有离子和疏水亲和力。随后，微凝胶通过酰腙-醛化学交联固定在原位凝胶水凝胶网络内，生成水凝胶-微凝胶软纳复合材料。这些纳米复合水凝胶的药物释放可持续长达 60 天，明显长于使用组成水凝胶或微凝胶单独（<1 周）的药物释放时间。通过改变微凝胶和水凝胶相对于药物-聚合物相互作用的亲和力以及水凝胶相的网络密度，很容易调节药物释放动力学。
