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.
Eur J Pharm Biopharm. 2018 Jun;127:150-158. doi: 10.1016/j.ejpb.2018.02.012. Epub 2018 Feb 10.
Liquid crystalline molecularly imprinted polymers (LC-MIPs) were low cross-linking MIPs (5-20 mol%) by introducing a LC monomer into the MIP polymerization system to keep the shape of the imprinted cavities due to additional interactions between the mesogenic groups. The multiwalled carbon nanotubes (MWCNTs) coated LC-MIP (MWCNT@LC-MIP) was the first fabricated as a novel floating interaction-controlled DDS. The synthesis was achieved by adding 9-vinylanthracene to obtain the high-density vinyl group functionalized MWCNTs firstly, and then polymerization of LC MIPs was performed on the surface of MWCNTs using a mixture of methacrylic acid, ethylene glycol dimethacrylate, and 4-methyl phenyl dicyclohexyl ethylene (LC monomer) with levofloxacin (LVF) as model template drug. Both template/functional monomer ratio and levels of crosslinker were optimized to obtain the best imprinting factor. Characterizations of polymer were investigated by the transmission electron microscope, nitrogen adsorption, thermogravimetric analysis, Fourier transform infrared spectra and floating behavior studies. The imprinting effect was confirmed by the adsorption isotherms, adsorption kinetics and effect of selectivity. In vitro release studies were examined by the LVF-loaded MWCNT@LC-MIP and the control samples, MWCNT@LC-NIP, MWCNT@MIP, MWCNT@NIP and the bare MWCNT using acetonitrile as the dissolute medium. The release profiles showed an obvious zero-order release of LVF from MWCNT@LC-MIP, which exhibited 3.8 μg/h of the release rate with duration of about 20 h. In vivo pharmacokinetic study displayed the relative bioavailability of the gastro-floating MWCNT@LC-MIP was 578.9%, whereas only 58.0% of MWCNT@MIP and 11.7% of the bared MWCNT. As a conclusion, MWCNT@LC-MIP showed potentials for oral administration by the innovative combination of floating and controlled release properties.
液晶分子印迹聚合物 (LC-MIPs) 是通过在 MIP 聚合体系中引入 LC 单体来实现的,该单体的交联度较低 (5-20 mol%),从而由于介晶基团之间的额外相互作用而保持印迹腔的形状。首先将 9-乙烯基蒽添加到多壁碳纳米管 (MWCNTs) 中,获得高密度乙烯基功能化 MWCNTs,然后在 MWCNTs 表面聚合 LC MIPs,使用甲基丙烯酸、乙二醇二甲基丙烯酸酯和 4-甲基苯基二环己基乙烯 (LC 单体) 与左氧氟沙星 (LVF) 作为模板药物进行聚合。通过优化模板/功能单体比和交联剂水平,获得最佳印迹因子。通过透射电子显微镜、氮气吸附、热重分析、傅里叶变换红外光谱和漂浮行为研究对聚合物进行了表征。通过吸附等温线、吸附动力学和选择性影响证实了印迹效应。通过载有 LVF 的 MWCNT@LC-MIP 和对照样品(MWCNT@LC-NIP、MWCNT@MIP、MWCNT@NIP 和裸 MWCNT)进行体外释放研究,使用乙腈作为溶解介质。释放曲线显示 LVF 从 MWCNT@LC-MIP 中呈现明显的零级释放,其释放速率为 3.8μg/h,持续约 20 h。体内药代动力学研究表明,胃漂浮 MWCNT@LC-MIP 的相对生物利用度为 578.9%,而 MWCNT@MIP 仅为 58.0%,裸 MWCNT 仅为 11.7%。总之,MWCNT@LC-MIP 结合漂浮和控制释放特性,为口服给药提供了潜力。