化学学报 ›› 2012, Vol. 70 ›› Issue (21): 2246-2250.DOI: 10.6023/A12070428 上一篇    下一篇

研究论文

基于葫芦[8]脲主-客体作用的温度及pH敏感壳聚糖超分子凝胶制备与性能

林友文, 李立凡, 李光文   

  1. 福建医科大学药学院 福州 350004
  • 收稿日期:2012-07-17 出版日期:2012-11-14 发布日期:2012-10-10
  • 通讯作者: 林友文 E-mail:linhumor@sina.com
  • 基金资助:
    项目受福建省自然科学基金计划项目(No. 2011J01289)和福建省科技计划重点项目(No. 2011Y0031)资助.

Preparation and Properties of Temperature and pH Sensitive Chitosan Supramolecular Gel Based on Host-guest Interaction of Cucurbit[8]uril

Lin Youwen, Li Lifan, Li Guangwen   

  1. College of Pharmacy, Fujian Medical University, Fuzhou 350004, China
  • Received:2012-07-17 Online:2012-11-14 Published:2012-10-10
  • Supported by:
    Project supported by the Natural Science Foundation of Fujian Province of China (No. 2011J01289) and the Key Project Foundation of Technology Plan of Fujian Province of China (No. 2011Y0031).

壳聚糖侧链改性合成N-(4-二甲氨基苯甲基)壳聚糖(MBCS), 通过葫芦[8]脲(Q[8])与MBCS侧链之间的主客体作用制得Q[8]/MBCS超分子凝胶. 利用红外光谱、紫外光谱、1H NMR、X-射线粉末衍射(XRD)、热重分析(TG)和差示扫描量热(DSC)等技术对改性壳聚糖及凝胶进行表征. 以5-氟尿嘧啶(5-Fu)为模型药物, 研究载药凝胶在不同pH环境下的释药行为. 结果表明Q[8]/MBCS体系在酸性条件下, 可组装形成超分子凝胶, 该凝胶体系具有温敏性和pH敏感性. 扫描电镜(SEM)图显示凝胶具有网状交联结构, 1H NMR谱显示, 在酸性条件下, Q[8]与MBCS含氮侧链基团间发生主客体包合作用是超分子凝胶形成的主要原因. Q[8]/MBCS载药凝胶在酸性介质中对药物具有明显的缓释作用.

关键词: 超分子凝胶, 葫芦[8]脲, 改性壳聚糖, 温敏性, pH敏感性, 释药

Chitosan (CS) which is a non-toxic, biocompatible, and biodegradable material and a good candidate for hydrogel formation was modified. A chitosan derivative, N-(4-dimethylaminobenzyl)chitosan (MBCS), was synthesized by the reaction of 4-(dimethylamino)benzaldehyde and chitosan to fabricate supramolecular gel system. The new family of macrocyclic host molecules, cucurbit[n]urils (Q[n], n=6~8) with its hydrophobic central cavity and negatively charged carbonyl portals, can bind to a variety of cationic organic guest molecules and neutral species to form the clathrate compounds with high affinity, and shows great potential applications in drug delivery system due to its low toxicity and good thermal stability. Cucurbit[8]uril (Q[8]) has a larger hydrophobic cavity volume of 479 ?3 and can include two aromatic rings. In this paper a novel supramolecular gel was prepared by utilizing the host-guest interaction between Q[8] and MBCS. The physical properties and structure of supramolecular gel and MBCS were characterized via IR, UV, 1H NMR, X-ray powder diffraction (XRD), thermogravimetric method (TG) and differential scanning calorimetry (DSC). The morphology of network structure of the xerogel was observed via an environmental scanning electron microscope (SEM). The spectrum of 1H NMR demonstrated that the host-guest interaction between Q[8] and guest units on the side chain of MBCS in the Q[8]/MBCS system resulted in the formation of the supramolecular gel. Q[8] acted as a cross-linker for supramolecular interactions (noncovalent crosslinking referring to electrostatic action, Van der Waals force and hydrophobic action, etc.). The Q[8]/MBCS supramolecular gel showed pH-sensitive and thermosensitive properties. 5-Fluorouracil (5-Fu) was taken as a model drug. The release characteristics of drug-loaded gels were studied in mediums with three different pH values. The results showed that the Q[8]/MBCS supramolecular gel system had obviously sustained-release for 5-Fu in acidic condition in vitro, suggesting that the Q[8]/MBCS supramolecular gel could be a new potential carrier for stimuli-responsive drug delivery system.

Key words: supramolecular gel, cucurbit[8]uril, modified chitosan, temperature sensitivity, pH sensitivity, drug release