Background: Protein drugs have disadvantages, such as short half-lives, unstable biological activities, and low utilization efficiency.

Objective: In this paper, a porous ion-responsive targeted drug delivery system was designed, combining biodegradable carriers with ion exchange technology to overcome problems for protein drug delivery systems.

Methods: Carboxymethyl Chitosan Porous Microspheres (CCPM) were prepared using an emulsification- chemical crosslinking method. Chitosan-bovine serum albumin-carboxymethyl chitosan porous microspheres (CBCCPM) were prepared using a dynamic ion exchange method and static self-assembly technology.

Results: CCPM were round in appearance mostly with a particle size distribution of 5-15 μm, which facilitates passive targeting to the lungs. CCPM had a total ion exchange capacity of 9.97 ± 0.07 mmol/g and showed a strong ability to attract and contain positively charged drugs. A potentiometric titration curve was used to identify the dissociation behavior of exchangeable groups on the microspheres; the optimal pH for ion exchange of microspheres was ≥ 4.3. CCPM had ion responsiveness, in vitro degradation ability, thermal stability and biocompatibility. In vitro release results confirmed that BSA and CCPM were mainly bound together by ionic bonds and the drug release mechanism of the self-assembled microspheres changed from particle diffusion to membrane diffusion under pH 7.4 PBS solution containing 0.02% Tween 80. Circular dichroism and sodium dodecyl-sulfate polyacrylamide gel electrophoresis results showed no significant change in the secondary structure and purity of BSA after binding to CCPM. The cumulative in vitro release rate of microspheres after 24 h was 86.78%.

Conclusion: In this paper, CBCCPM, a porous ion-responsive targeted drug delivery system, was designed.

背景：蛋白药物具有诸如半衰期短，生物活性不稳定和利用效率低等缺点。

目的：本文设计了一种多孔离子响应靶向药物递送系统，将可生物降解的载体与离子交换技术相结合，以克服蛋白质药物递送系统的问题。

方法：采用乳化-化学交联法制备羧甲基壳聚糖多孔微球（CCPM）。采用动态离子交换法和静态自组装技术制备了壳聚糖-牛血清白蛋白-羧甲基壳聚糖多孔微球（CBCCPM）。

结果：CCPM的外观呈圆形，大部分粒径分布为5-15μm，有利于被动靶向肺。CCPM的总离子交换容量为9.97±0.07 mmol / g，显示出强大的吸引和容纳带正电荷药物的能力。用电位滴定曲线确定微球上可交换基团的离解行为。微球离子交换的最佳pH≥4.3。CCPM具有离子响应性，体外降解能力，热稳定性和生物相容性。体外释放结果证实，BSA和CCPM主要通过离子键结合在一起，并且自组装微球的药物释放机制在pH 7.4含0.02％Tween 80的PBS溶液中从颗粒扩散变为膜扩散。圆二色性和十二烷基硫酸钠聚丙烯酰胺凝胶电泳结果表明，与CCPM结合后，BSA的二级结构和纯度没有明显变化。24小时后微球的体外累积释放率为86.78％。

结论：本文设计了一种多孔离子响应靶向药物递送系统CBCCPM。