聚合物复合物层层组装膜的高效负载及大分子和小分子药物的差别性释放

基于聚合物复合物和层层组装技术实现了大分子药物硫酸软骨素和小分子药物头孢曲松钠在聚合物膜中的高效负载以及差别性释放. 壳聚糖(CHI)和大分子药物硫酸软骨素(CSS)通过静电相互作用力复合, 制备了壳聚糖-硫酸软骨素复合物(CHI-CSS). 以CHI-CSS复合物和透明质酸(HA)为构筑基元, 通过层层组装构筑负载有硫酸软骨素的聚合物复合物膜. 利用后扩散的负载方法将小分子药物头孢曲松钠(CTX)负载到聚合物膜中, 从而实现大分子和小分子2种药物在聚合物膜中的负载. 聚合物膜中负载的CTX和CSS在生理条件下具有快慢不同的差别性释放动力学特性, CTX在6 h内快速释放, 而CSS长效缓释长达14 d. 快速释放的抗生素CTX能够有效抑制细菌感染, 而酶降解作用下缓慢释放的CSS可促进伤口愈合, 在包括头颈外科在内的外科术后感染防治领域有良好应用前景.

Layer-by-layer Assembled Polymeric Complexes Films for High Loading and Differential Release of Macromolecular and Small Molecular Drugs†

The layer-by-Layer(LbL) assembled polymeric complexes films capable of differential release of macromolecular and small molecular drugs were fabricated by utilizing chitosan(CHI) hydrochloride-chondroitin sulfate sodium(CSS) complexes(denoted as CHI-CSS complexes) as building blocks and post-diffusion of ceftriaxone sodium(CTX). The CHI-CSS complexes were prepared by pre-assembled macromolecular drugs CSS with CHI, and then were LbL assembled with hyaluronic acid(HA) to produce CHI-CSS/HA polymeric films. The small molecular drugs CTX were loaded into the CHI-CSS/HA polymeric films through a postdiffusion process. The as-prepared CHI-CSS/HA polymeric films possess high loading capacity because of the high encapsulation amount of CSS in CHI-CSS complexes and plenty of electrostatic binding sites for CTX provided by film component CHI. CTX can be quickly released from the polymeric films because of the brea-kage of its electrostatic interaction with film component CHI. Meanwhile, the CSS can be released in sustained manner by enzymatic degradation of the films. The synergetic therapeutic effects can be achieved by fast release of antibiotic drug CTX to effectively eliminate bacteria and by sustained release of CSS to promote wound healing. The present work provides a facile way to fabricate polymeric films for high loading and diffe-rential release of multiple therapeutic agents.