Liang Ge, Jia-Bi Zhu, Fei Xiong, Bin Ni
School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China.
J Pharm Pharmacol. 2007 May;59(5):661-7. doi: 10.1211/jpp.59.5.0006.
The objective of this work was to investigate the preparation, characterization and pharmacokinetics of N-palmitoyl chitosan anchored docetaxel liposomes. To decrease toxic effects and improve antitumour efficacy of the drug, docetaxel has been incorporated in liposomes; the formulation, stability and pharmacokinetics of plain docetaxel liposomes (PDLs), PEGylated docetaxel liposomes (PEGDLs) and N-palmitoyl chitosan anchored docetaxel liposomes (NDLs) were compared. NDL was more stable than PDL and PEGDL in-vitro, especially in the presence of serum at 37 degrees C. The concentration of docetaxel in the plasma of rats after intravenous administration of docetaxel injection, PDL, PEGDL and NDL was studied by RP-HPLC. The pharmacokinetic behaviour of docetaxel injection, PDL, PEGDL and NDL were significantly different. These findings suggest that anchored liposomes could increase the stability of docetaxel in-vivo, as compared with plain liposomes, but the improvement was not more significant than PEGylated liposomes. N-Palmitoyl chitosan as a new polymeric membrane to anchor liposome was useful to stabilize liposomes containing anti-tumour drug.
本研究旨在考察N-棕榈酰壳聚糖锚定多西他赛脂质体的制备、表征及药代动力学。为降低药物的毒副作用并提高其抗肿瘤疗效，已将多西他赛载入脂质体；比较了普通多西他赛脂质体（PDLs）、聚乙二醇化多西他赛脂质体（PEGDLs）和N-棕榈酰壳聚糖锚定多西他赛脂质体（NDLs）的制剂、稳定性及药代动力学。NDL在体外比PDL和PEGDL更稳定，尤其是在37℃有血清存在的情况下。采用反相高效液相色谱法（RP-HPLC）研究了大鼠静脉注射多西他赛注射液、PDL、PEGDL和NDL后血浆中多西他赛的浓度。多西他赛注射液、PDL、PEGDL和NDL的药代动力学行为存在显著差异。这些结果表明，与普通脂质体相比，锚定脂质体可提高多西他赛在体内的稳定性，但改善程度不如聚乙二醇化脂质体。N-棕榈酰壳聚糖作为一种新型的脂质体锚定聚合物膜，有助于稳定含抗肿瘤药物的脂质体。
