College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
Int J Pharm. 2010 Feb 15;386(1-2):221-8. doi: 10.1016/j.ijpharm.2009.11.024. Epub 2009 Nov 27.
A series of branched cationic beta-cyclodextrin polymers (CPbetaCDs) with designed chemical structures were synthesized from beta-cyclodextrin (beta-CD), epichlorohydrin (EP) and choline chloride (CC). Indomethacin (IDM), an anionic drug, was chosen as a model drug to evaluate the drug loading capacities of CPbetaCDs. The formation of IDM-CPbetaCD complex was confirmed by (1)H NMR and DSC. Phase solubility studies and Job plots indicated that CPbetaCDs can solubilize IDM up to 100 times of its intrinsic solubility in a 1:1 complexation form. Mechanism studies with the help of adamantane revealed that the effective complexation is a combination of inclusion complexation, charge interaction and hydrophobic interaction. In addition, IDM-CPbetaCDs loaded alginate hydrogels were prepared and obtained controllable release profile in dissolution tests. The tunable structures of CPbetaCDs make them promising drug carriers with superior drug loading capacities and controllable drug release abilities.
一系列具有设计化学结构的支链阳离子β-环糊精聚合物(CPβCDs)由β-环糊精(β-CD)、表氯醇(EP)和氯化胆碱(CC)合成。选择吲哚美辛(IDM)作为模型药物来评估 CPβCDs 的载药能力。通过 1H NMR 和 DSC 证实了 IDM-CPβCD 复合物的形成。相溶解度研究和 Job 图表明,CPβCDs 可以将 IDM 的溶解度提高到其固有溶解度的 100 倍,形成 1:1 的复合物形式。借助金刚烷的机制研究表明,有效的络合是包合络合、电荷相互作用和疏水相互作用的结合。此外,还制备了负载 IDM 的 CPβCDs 载药海藻酸钠水凝胶,并在溶解试验中获得了可控制的释放曲线。CPβCDs 的可调结构使它们成为具有高载药能力和可控制释放能力的有前途的药物载体。