College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
Int J Pharm. 2014 Apr 10;464(1-2):127-34. doi: 10.1016/j.ijpharm.2014.01.015. Epub 2014 Jan 19.
Doxorubicin (DOX)-loaded nanoparticles based on polyethylene glycol-conjugated chitosan oligosaccharide-arachidic acid (CSOAA-PEG) were explored for potential application to leukemia therapy. PEG was conjugated with CSOAA backbone via amide bond formation and the final product was verified by (1)H NMR analysis. Using the synthesized CSOAA-PEG, nanoparticles having characteristics of a 166-nm mean diameter, positive zeta potential, and spherical shape were produced for the delivery of DOX. The mean diameter of CSOAA-PEG nanoparticles in the serum solution (50% fetal bovine serum) remained relatively constant over 72 h as compared with CSOAA nanoparticles (changes of 20.92% and 223.16%, respectively). The sustained release pattern of DOX from CSOAA-PEG nanoparticles was displayed at physiological pH, and the release rate increased under the acidic pH conditions. The cytotoxicity of the CSOAA-PEG conjugate was negligible in human leukemia cells (K562) at the concentrations tested (∼ 100 μg/ml). The uptake rate of DOX from the nanoparticles by K562 cells was higher than that from the solution. Judging from the results of pharmacokinetic studies in rats, in vivo clearance rate of DOX from the CSOAA-PEG nanoparticle group was slower than other groups, subsequently extending the circulation period. The PEGylated CSOAA-based nanoparticles could represent an effective nano-sized delivery system for DOX which has been used for the treatment of blood malignancies.
载多柔比星（DOX）的纳米粒基于聚乙二醇接枝壳聚糖寡糖-花生酸（CSOAA-PEG）被探索用于白血病治疗的潜在应用。PEG 通过酰胺键形成与 CSOAA 主链连接，最终产物通过（1）H NMR 分析进行验证。使用合成的 CSOAA-PEG，制备了具有 166nm 平均直径、正 zeta 电位和球形的纳米粒用于 DOX 的递送。与 CSOAA 纳米粒（分别变化 20.92%和 223.16%）相比，在含 50%胎牛血清的血清溶液中 CSOAA-PEG 纳米粒的平均直径在 72 小时内保持相对恒定。在生理 pH 下，CSOAA-PEG 纳米粒中 DOX 呈现持续释放模式，在酸性 pH 条件下释放速率增加。在测试浓度（约 100μg/ml）下，CSOAA-PEG 缀合物对人白血病细胞（K562）的细胞毒性可以忽略不计。K562 细胞从纳米粒中摄取 DOX 的速率高于从溶液中摄取的速率。从大鼠药代动力学研究的结果来看，CSOAA-PEG 纳米粒组中 DOX 的体内清除率比其他组慢，从而延长了循环周期。基于 PEG 化 CSOAA 的纳米粒可以代表一种有效的 DOX 纳米递药系统，已用于治疗血液恶性肿瘤。
