Shen Shigang, Li Haiying, Yang Wenzhi
College of Chemistry and Environmental Science, Hebei University , Baoding , PR China and.
Drug Deliv. 2014 Nov;21(7):501-8. doi: 10.3109/10717544.2014.895068. Epub 2014 Mar 13.
To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by 1H NMR was 5.2 cholesterol groups per hundred glucose units. CHSPNs were prepared in aqueous media and characterized by dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM). These nanoparticles were almost spherical in shape, and the zeta potentials of CHSPNs were near zero in aqueous media. CHSPNs can be stable at least 2 months with no significant size and zeta potential changes. Single dose toxicity test in mice was investigated for the safety evaluation of CHSPNs as a drug nanocarrier, and the result showed CHSPNs were well tolerated at the dose of 200 mg/kg in mice. Epirubicin (EPI)-loaded CHSPNs (EPI-CHSPNs) were prepared and the in vivo pharmacokinetics and biodistribution were studied. Compared with the EPI solution, EPI-CHSPNs have exhibited higher plasma drug concentration, longer half-life time (t(1/2)) and the larger area under-the-curve (AUC). Moreover, the drug level of EPI-CHSPNs increased in liver and decreased in heart. The results indicated that CHSPNs were stable, safe and may be a promising drug delivery carrier.
为了进一步开发胆固醇修饰的普鲁兰多糖自聚集纳米颗粒（CHSPNs）作为药物纳米载体，合成并表征了胆固醇修饰的普鲁兰多糖（CHSP）。通过1H NMR测定其胆固醇含量为每100个葡萄糖单元含有5.2个胆固醇基团。在水介质中制备了CHSPNs，并通过动态激光散射（DLS）、zeta电位和透射电子显微镜（TEM）对其进行了表征。这些纳米颗粒几乎呈球形，在水介质中CHSPNs的zeta电位接近零。CHSPNs可以稳定至少2个月，尺寸和zeta电位无明显变化。对小鼠进行了单剂量毒性试验，以评估CHSPNs作为药物纳米载体的安全性，结果表明CHSPNs在小鼠体内200mg/kg剂量下耐受性良好。制备了载表柔比星（EPI）的CHSPNs（EPI-CHSPNs），并研究了其体内药代动力学和生物分布。与EPI溶液相比，EPI-CHSPNs表现出更高的血浆药物浓度、更长的半衰期（t(1/2)）和更大的曲线下面积（AUC）。此外，EPI-CHSPNs在肝脏中的药物水平升高，在心脏中的药物水平降低。结果表明，CHSPNs稳定、安全，可能是一种有前途的药物递送载体。
