Department of Physiology, College of Basic Medicine, Shenyang Medical College, Shenyang, China.
Department of Electrical Diagnosis, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.
Drug Deliv. 2020 Dec;27(1):1156-1164. doi: 10.1080/10717544.2020.1797243.
In this work, we prepared a stimuli-responsive system for drug delivery and controlled release by engineering the bovine serum albumin (BSA). The doxorubicin (DOX)-loaded BSA nanoparticles (NPs) were conveniently prepared using desolvation method, followed by crosslinking through Schiff base bonds, leading to pH-sensitive DOX-loaded system (DOX@BSA NPs). The resulted DOX@BSA NPs showed high drug loading capacity (21.4%), and the particle size was about 130 nm with narrow polydispersity and high negative surface charge (-20.5 mV). The pH-sensitivity of DOX@BSA NPs was evidenced by the size changes and charge reversal after incubation at different pH values. The DOX@BSA NPs showed high serum stability which indicated the prolonged circulation time. The drug release experiment showed that the release of DOX was obviously accelerated by acidity because of disassembly of NPs induced by cleavage of Schiff base bonds. The drug release mechanism was thoroughly studied using a semi-empirical model, further confirming the pH played an important role in drug controlled release process. The results of cytotoxicity assay revealed that DOX@BSA NPs exhibited much higher toxic effects for tumor cells in comparison to the free DOX control. Collectively, these results demonstrated that DOX@BSA NPs might be potential application for drug delivery and controlled release in cancer chemotherapy. Moreover, this work also showed that preparation of stimuli-responsive drug delivery system by engineering the commercial biomaterials could be a promising method to develop multi-functional nanomedicine.
在这项工作中，我们通过工程化牛血清白蛋白（BSA）制备了一种用于药物输送和控制释放的刺激响应系统。通过去溶剂化法方便地制备了载阿霉素（DOX）的 BSA 纳米颗粒（NPs），然后通过席夫碱键交联，得到 pH 敏感的载 DOX 系统（DOX@BSA NPs）。所得的 DOX@BSA NPs 具有高载药能力（21.4%），粒径约为 130nm，具有较窄的多分散性和高负表面电荷（-20.5mV）。DOX@BSA NPs 的 pH 敏感性通过在不同 pH 值下孵育后的粒径变化和电荷反转得到证实。DOX@BSA NPs 具有高血清稳定性，表明其循环时间延长。药物释放实验表明，由于席夫碱键的断裂导致 NPs 解体，DOX 的释放明显被酸性加速。通过半经验模型深入研究了药物释放机制，进一步证实了 pH 在药物控制释放过程中起着重要作用。细胞毒性实验结果表明，与游离 DOX 对照组相比，DOX@BSA NPs 对肿瘤细胞具有更高的毒性作用。总的来说，这些结果表明 DOX@BSA NPs 可能是癌症化疗中药物输送和控制释放的潜在应用。此外，这项工作还表明，通过工程化商业生物材料制备刺激响应药物输送系统可能是开发多功能纳米医学的一种有前途的方法。
