Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Int J Pharm. 2017 Oct 30;532(1):365-373. doi: 10.1016/j.ijpharm.2017.09.008. Epub 2017 Sep 6.
Liquid crystalline-molecularly imprinted polymer (LC-MIP) particles were first found to possess the floating behavior on the aqueous medium. Combined with molecular recognition, the LC-MIP was fabricated as a novel class of the controlled-release gastric retentive DDS. The LC-MIP was made using co-polymerization of methacrylic acid, 4-methyl phenyl dicyclohexyl ethylene (LC monomer with vinyl group), and ethylene glycol dimethacrylate with S-amlodipine (S-AML) as model template drug. The optimum condition of the preparation of LC-MIP has been obtained relying on release behaviors of S-AML from the LC-MIP. The surface morphology of LC-MIP and three corresponding control samples, i.e., template-free LC-NIP, LC-free MIP, and LC-free NIP, were studied. Applying the LF model for the binding isotherm, imprinting factors was 2.80 for the LC-MIP with the crosslinking degree of 20.0%, whereas 6.70 for the LC-free MIP with high levels of crosslinker (80.0%). Furthermore, the phase transition behaviors of LC-based particles as well as drug-loaded LC elastomers were measured by a differential scanning calorimeter and the formed hydrogen bonding between S-AML and LC-MIP was demonstrated by FT-IR spectra. In vivo imaging experiment proved that the floating LC-MIP had significantly longer gastric residence time (>60min) than the non-floating MIP reference (<30min). In vivo pharmacokinetic study showed a plateau region between 1.5 and 22h on the plasma concentration from the LC-MIP. In spite of lower imprinting factor, the relative bioavailability of the gastro-floating LC-MIP was 180.5%, whereas only 111.7% of the LC-free MIP. As a conclusion, the LC-MIPs indicated potentials for oral administration due to the innovative combination of floating and controlled release properties.
液晶分子印迹聚合物（LC-MIP）颗粒最初被发现具有在水介质中漂浮的行为。结合分子识别，LC-MIP 被制备为一类新型的控释胃滞留 DDS。LC-MIP 是由甲基丙烯酸、4-甲基苯基二环己基乙烯（带乙烯基的 LC 单体）和乙二醇二甲基丙烯酸酯与 S-氨氯地平（S-AML）共聚而成，作为模型模板药物。通过 S-AML 从 LC-MIP 中的释放行为，获得了制备 LC-MIP 的最佳条件。研究了 LC-MIP 及其三个相应对照样品（无模板 LC-NIP、无 LC 的 MIP 和无 LC 的 NIP）的表面形态。应用 LF 模型进行结合等温线，印迹因子为交联度为 20.0%的 LC-MIP 为 2.80，而交联剂水平较高的无 LC 的 MIP 为 6.70（80.0%）。此外，通过差示扫描量热法测量了基于 LC 的颗粒以及载药 LC 弹性体的相变行为，并通过 FT-IR 光谱证明了 S-AML 和 LC-MIP 之间形成的氢键。体内成像实验证明，漂浮的 LC-MIP 比非漂浮的 MIP 对照（<30min）具有显著更长的胃停留时间（>60min）。体内药代动力学研究表明，LC-MIP 的血浆浓度在 1.5 至 22 小时之间存在平台区。尽管印迹因子较低，但胃漂浮 LC-MIP 的相对生物利用度为 180.5%，而无 LC 的 MIP 仅为 111.7%。总之，由于漂浮和控释特性的创新结合，LC-MIP 具有口服给药的潜力。
