State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Biomed Pharmacother. 2012 Feb;66(1):46-51. doi: 10.1016/j.biopha.2011.09.010. Epub 2011 Dec 30.
A N-octyl-O-sulfate chitosan (NOSC) anchored liposome system was developed as the carrier for antitumor drug, docetaxel (DTX). The physicochemical and pharmacokinetic properties of NOSC-modified DTX liposomes (NDLs) were evaluated compared with the conventional DTX liposomes (DLs) and commercial dosage form of DTX, Taxotere(®). The results showed that NDLs had DTX-loading rate of 3.41%, entrapment efficiency of 61.73%, narrow distributed particle size of 147.6±1.9nm, and high zata potential of -44.2±3.9mV. The decreased permeability of the liposome bilayer was evaluated by release behavior of calcein (CAL) from the internal phase of NOSC-modified CAL liposomes (NCLs) and enhanced stability of NDLs owed to shielding effect of sulfonic shell from adsorption by BSA. After i.v. administration at the dose of 12mg/kg, a significant increase in the AUC, MRT, and T(1/2β) (P<0.05) was observed in NDLs group compared with DLs and Taxotere(®) group. AUC(0-∞) of NDLs was 6.14 and 1.55 times higher than Taxotere(®) and DLs, respectively, and MRT(0-∞) of NDLs was 5.77 and 1.37 times higher than Taxotere(®) and DLs, respectively. All these results suggested that anchored liposomes could increase the stability of DTX in vitro and in vivo, as compared with conventional liposomes and Taxotere(®). Therefore, NOSC as a polymeric shell to liposomes was effective to enhance the stability of liposomes containing DTX.
一种八辛基-O-硫酸化壳聚糖（NOSC）锚定脂质体系统被开发为抗肿瘤药物多西他赛（DTX）的载体。与传统的 DTX 脂质体（DLs）和多西他赛的商业剂型 Taxotere(®)相比，评估了 NOSC 修饰的 DTX 脂质体（NDLs）的理化性质和药代动力学性质。结果表明，NDLs 的 DTX 载药量为 3.41%，包封率为 61.73%，粒径分布较窄，为 147.6±1.9nm，Zata 电位为-44.2±3.9mV。通过 NOSC 修饰的 CAL 脂质体（NCLs）内部相的 calcein（CAL）释放行为评估脂质体双层的通透性降低，并且由于磺酸壳的屏蔽作用，NDLs 的稳定性增强，从而避免了与 BSA 的吸附。在 12mg/kg 的剂量静脉给药后，与 DLs 和 Taxotere(®)组相比，NDLs 组的 AUC、MRT 和 T(1/2β)显著增加（P<0.05）。NDLs 的 AUC(0-∞)分别是 Taxotere(®)和 DLs 的 6.14 倍和 1.55 倍，MRT(0-∞)分别是 Taxotere(®)和 DLs 的 5.77 倍和 1.37 倍。所有这些结果表明，与传统脂质体和 Taxotere(®)相比，锚定脂质体可以增加 DTX 在体外和体内的稳定性。因此，NOSC 作为脂质体的聚合物外壳，可以有效地提高含有 DTX 的脂质体的稳定性。
