Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Int J Pharm. 2020 Feb 15;575:118845. doi: 10.1016/j.ijpharm.2019.118845. Epub 2019 Dec 10.
The objective of this study was to develop a thermoresponsive injectable hydrogel for the sustained release of drugs by taking advantage of host-guest interactions between a hydrophobically modified hydroxypropylmethyl cellulose (HM-HPMC) and cyclodextrin (CD). A thermoresponsive injectable hydrogel was prepared by simply adding CDs to HM-HPMC hydrogel. The HM-HPMC hydrogel was converted into a sol with a low viscosity through host-guest interactions with CDs. The HM-HPMC/β-CD hydrogel became a gel near body temperature where the host dissociated from the hydrophobic moieties of the polymer in response to the temperature. The yield stress of the HM-HPMC became progressively lower on the addition of β-CD which was desirable in the case of developing an injectable formulation. When the HM-HPMC/β-CD hydrogel containing indocyanine green (ICG) was subcutaneously administered to mice, the fluorescence of the ICG remained relatively constant for 24 h after the administration, which was substantially longer than that for ICG alone or an HPMC formulation. The plasma insulin level was maintained for a longer period of time when the HM-HPMC/β-CD containing insulin was administered and the MRT value was increased by 1.6 times compared to a solution of insulin alone. In addition, the HM-HPMC/β-CD hydrogel formulation showed a prolonged hypoglycemic effect in response to the insulin which was slowly released from the hydrogel. A thermoresponsive injectable hydrogel was successfully constructed from the highly viscous HM-HPMC and β-CD, and the resulting formulation functioned as a sustained release carrier for drugs.
本研究旨在利用疏水改性羟丙甲纤维素（HM-HPMC）与环糊精（CD）之间的主体-客体相互作用，开发一种用于药物持续释放的温敏型可注射水凝胶。通过向 HM-HPMC 水凝胶中添加 CD，制备了温敏型可注射水凝胶。HM-HPMC 水凝胶通过与 CD 的主体-客体相互作用转变为低粘度的溶液。HM-HPMC/β-CD 水凝胶在接近体温时变成凝胶，其中主体从聚合物的疏水部分解离，以响应温度。随着β-CD 的加入，HM-HPMC 的屈服应力逐渐降低，这在开发可注射制剂的情况下是理想的。当皮下给予含有吲哚菁绿（ICG）的 HM-HPMC/β-CD 水凝胶时，ICG 的荧光在给药后 24 小时内保持相对稳定，这明显长于 ICG 单独或 HPMC 制剂。当给予含有胰岛素的 HM-HPMC/β-CD 时，血浆胰岛素水平保持更长时间，MRT 值与胰岛素单独溶液相比增加了 1.6 倍。此外，HM-HPMC/β-CD 水凝胶制剂在胰岛素从水凝胶中缓慢释放时表现出延长的降血糖作用。成功地从高粘度的 HM-HPMC 和β-CD 构建了温敏型可注射水凝胶，所得制剂作为药物的持续释放载体发挥作用。
