戊二醛交联白蛋白纳米载体的制备及载药性能研究

Study on preparation and drug loading performance of glutaraldehyde crosslinked albumin nanoparticles

目的 制备戊二醛交联牛血清白蛋白纳米载体(bovine serum albumin nanoparticles, BSA-NPs),并研究其对模型药物(阿霉素盐酸盐和硫酸鱼精蛋白)的载药性能。方法 以乙醇为脱水剂,以戊二醛为交联剂,通过去溶剂化法制备BSA-NPs。通过脱水剂用量、交联剂用量、BSA浓度、反应温度等因素优化BSA-NPs性能,并通过载药量、包封率和药物释放行为,考察BSA-NPs对模型药物的载药性能。结果当脱水剂与蛋白溶液体积比为1∶1,戊二醛与BSA投料比为26.7μg/mg,BSA浓度为3%(m/v),反应温度为30℃时,所得BSA-NPs具有相对较小的粒径[(112.7±3.9)nm]和粒度分布(PDI为0.19±0.01),Zeta电位为(-20.7±1.7) mV。优化后的BSA纳米载体对模型药物的载药量、包封率和48 h体外累积释放量分别为:阿霉素盐酸盐(10.2%,71.8%,73.9%),硫酸鱼精蛋白(6.5%,54.7%,34.8%)。结论成功制备BSA-NPs,其对亲水性小分子(阿霉素盐酸盐)和大分子模型药物(硫酸鱼精蛋白)均表现出了较好的、有差异化的载药能力和药物缓释性能。

Objective To prepare glutaraldehyde crosslinked bovine serum albumin nanoparticles(BSA-NPs)and study their drug loading performance for model drugs of hydrophilic small molecule(doxorubicin hydrochloride)and macromolecule(protamine sulfate).Methods Glutaraldehyde crosslinked BSA nanoparticles were prepared by desolvation method using ethanol as the dehydrating agent and glutaraldehyde as the crosslinking agent.The properties of BSA nanoparticles were optimized by the amount of dehydrating agent,the amount of crosslinking agent,the concentration of BSA and the reaction temperature.The drug loading and release properties of BSA-NPs for model drugs were investigated by drug loading content,drug loading efficiency and drug release profiles.Results When the volume ratio of dehydrating agent to protein solution was 1:1,the feeding ratio of glutaraldehyde to BSA was 26.7μg/mg,the concentration of BSA was 3%(m/v),the reaction temperature was 30℃,the obtained BSA nanoparticles had relatively small particle size[(112.7±3.9)nm]and particle size distribution(PDI:0.19±0.01),and Zeta potential was(-20.7±1.7)mV.The drug loading content,drug loading efficiency and 48 h cumulative release of the model drugs were as follows:doxorubicin hydrochloride(10.2%,71.8%,73.9%)and protamine sulfate(6.5%,54.7%,34.8%).Conclusion BSA-NPs were successfully synthesized and showed good and differentiated drug loading capacity and sustained drug release profiles for hydrophilic small molecules(doxorubicin hydrochloride)and macromolecular model drugs(protamine sulfate).