Potential doxorubicin delivery system based on magnetic gelatin microspheres crosslinked with sugars

Abstract The preparation and characterization of magnetic microspheres based on gelatin for use in drug delivery systems are reported. Sugars were employed as crosslinking agents and type A gelatin and type B gelatin were compared to prepare microspheres by water-in-oil emulsion. The influence of gelatin and sucrose concentration, temperature and stirring speed on microbeads’ characteristics was studied. The gelatin concentration and stirring speed were the parameters directly associated with the particle sizes. We found no relevant difference between the use of type A and type B gelatin. In addition, the gelatin crosslinking study revealed that sucrose is not a crosslinking agent but fructose can crosslink the protein chains when the reaction medium has pH 9. The size of the microspheres varied from 5 to 60 μm as measured by optical microscopic images. Doxorubicin adsorption and release were successfully performed using the microspheres crosslinked with fructose under the action of an external magnetic field. It was observed that the microspheres absorbed 69% of the doxorubicin that was in solution. After 24 h, about 45% of the DOX was displaced from microspheres to saline medium in the free form in the solution.

摘要：本研究报道了用于药物递送系统的明胶基磁性微球的制备与表征工作。以糖类作为交联剂，通过油包水乳液法分别以A型明胶与B型明胶为原料制备微球，并对二者进行对比分析。考察了明胶与蔗糖浓度、反应温度及搅拌速率对微球性能的影响。研究发现，明胶浓度与搅拌速率是直接影响微球粒径的参数，且未观察到A型与B型明胶在使用效果上存在显著差异。此外，明胶交联实验结果表明，蔗糖并非有效交联剂；而当反应体系pH为9时，果糖可与蛋白质链发生交联。通过光学显微镜成像测得，微球粒径范围为5~60 μm。以果糖交联的微球为载体，在外加磁场作用下成功完成了阿霉素（Doxorubicin，DOX）的吸附与体外释放实验：实验测得该微球可吸附溶液中69%的阿霉素；孵育24 h后，约45%的DOX以游离形式从微球中释放至生理盐水介质中。