基于敏感断裂键的多孔分子印迹材料的制备及药物控释研究

The drawback in traditional preparation method for molecularly imprinted polymers (MIPs) mainly involves the deep and heterogeneous location of recognition cavities, binding sites in the polymer matrix, rate limitations of mass transfer and accessibility of the target molecules. In this proposal, we present a strategy to synthesize porous MIPs based on sensitive cleavable linkages for drug controlled release. The inner porous structure of MIPs is prepared by the reductive degradation of polymers with internal disulfide linkages, which can expose more effective recognition sites and increase the adsorption ability of MIPs. First, we synthesize the linear polymer as a matrix to prepare porous MIPs, and evaluate the pore forming ability of cleavable disulfide bonds. Then, we synthesize hyperbranched polymers with defined numbers of azido-terminated functionalities; following introduce the block copolymer containing disulfide bonds via click reaction. As a comparison, we also synthesize hyperbranched polymers containing alkali-cleavable disulfide one-step. The two kinds of hyperbranched polymers are also used as matrix to prepare porous MIPs. At last, the porous MIPs are prepared using sulfasalazine or doxorubicin as template molecule. The selective recognizing adsorption ability and potential as drug carrier of the porous MIPs for template molecule are evaluated, which can reveal the effect of the inner located binding cavities for excellent accessibility and affinity toward template, desirable efficiency for template removal and rebinding, and the ability of drug controlled release. The expected achievement of this proposal will offer a strategy for preparing the porous and functional MIPs, which possesses great scientific potentials for the improvement of molecular imprinting technique.

印迹空穴包埋过深、结合位点不均一、可接近性差、识别动力学慢等是传统分子印迹技术中存在的主要问题，本项目提出基于敏感断裂键的多孔分子印迹材料（MIPs）制备及药物控释研究的思路，利用交联聚合物中双硫键的还原断裂特性在MIPs中形成多孔通道，暴露更多有效识别位点，提高吸附性能。首先从线性聚合物出发，探索还原敏感断裂双硫键在MIPs制备过程中的致孔作用；然后合成末端叠氮基团数目可控的超支化聚合物，经点击化学引入可断裂双硫键嵌段结构；并一步合成含双硫键的超支化聚合物，作为基质制备多孔MIPs。最后分别以柳氮磺胺吡啶和阿霉素为模板分子，制备多孔MIPs并对其吸附载药性能及药物缓释行为进行研究，揭示MIPs的多孔性与有效吸附位点、模板分子脱除、再结合及载药缓释能力之间的联系。通过该项目的实施，可为MIPs结构和功能提升及多样化提供新思路，在分子印迹科学发展迈向更深入层次的今天，具有重要的学术研究价值。

分子印迹技术采用人工模拟方法制备对模板分子具有特异性识别能力的具有三维立体结构的聚合物，可用于选择性分离、检测以及富集复杂基质中的目标分子。分子印迹聚合物材料在色谱分离、仿生传感器、催化、药物传递以及固相萃取等方面显示出广泛的应用前景。本项目中鉴于印迹空穴包埋过深、结合位点不均一、可接近性差、识别动力学慢等传统分子印迹技术中存在的主要问题，首先提出基于敏感断裂降解超支化聚合物的多孔分子印迹材料（MIPs）制备及药物控释研究的思路，利用交联聚合物中双硫键的还原断裂特性在MIPs中形成多孔通道，暴露更多有效识别位点，提高吸附性能。分别以阿霉素和盐酸硫胺素作为模板分子，制备多孔MIPs并对其吸附载药性能及药物缓释行为进行研究，揭示MIPs的多孔性与有效吸附位点、模板分子脱除、再结合及载药缓释能力之间的联系。通过温和化学方法裂解超支化聚合物制备多孔分子印迹材料改善药物负载以及释放行为，在药物输送系统研究中具有良好的潜在应用。同时针对传统的分子印迹包埋型聚合制备方法所带来的有效结合位点比例低、洗脱结合速率较慢、吸附容量偏低等缺点，在项目执行期间进一步开展了以纳米材料为基质的表面分子印迹技术相关工作。纳米结构的分子印迹材料具有较高的比表面积，选择识别位点大多位于基质表面，所以表现出较大的结合容量和快的结合动力学特性，展示了良好的应用前景。