Cheng Ji, Zhu Jia-bi, Wen Na, Xiong Fei
School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
Int J Pharm. 2006 Apr 26;313(1-2):136-43. doi: 10.1016/j.ijpharm.2006.01.031. Epub 2006 Mar 15.
Modified polysaccharides have been used widely to increase physico-chemical stability of liposomes. However, the stability and pharmacokinetic studies on the polysaccharides modified anchored liposomes containing hydrophobic drugs which exist in lipid bilayer membranes were insufficient as compared with the liposomes carrying hydrophilic or ionic drugs in inner aqueous phase. In the present study, a hydrophobic drug, dipyridamole (DIP), was entrapped into liposomes through film hydration. Amylopectin was palmitoylated and anchored on the surface of plain DIP liposomes. Subsequently, the stabilities of DIP ethanol solution, plain DIP liposomes (PDL) and anchored DIP liposomes (ODL) against irradiation, disperse medium, biofluid, long-term storage were determined and compared. The concentrations of DIP in plasma of rats and its pharmacokinetic behaviors after intravenous administration of DIP injection, PDL and ODL were studied by RP-HPLC. The pharmacokinetic parameters were computed by software 3p97 programme. The results showed that ODL could increase stabilities more of DIP in vitro as compared with PDL. The plasma concentration-time curves of DIP after intravenous administration of DIP injection, PDL and ODL were all in accordance with open two-compartment model. Pharmacokinetic parameters of DIP injection, PDL and ODL in rats were significantly different. The present findings suggest that anchored liposomes could increase stabilities of DIP in vitro as compared with plain liposomes. Furthermore, the difference of pharmacokinetic profiles was due to the targetability of anchored liposomes.
改性多糖已被广泛用于提高脂质体的物理化学稳定性。然而，与载有亲水性或离子性药物的内水相脂质体相比，对存在于脂质双分子层膜中的含疏水药物的多糖修饰锚定脂质体的稳定性和药代动力学研究还不够充分。在本研究中，通过薄膜水化法将疏水药物双嘧达莫（DIP）包封到脂质体中。支链淀粉经棕榈酰化后锚定在普通DIP脂质体表面。随后，测定并比较了DIP乙醇溶液、普通DIP脂质体（PDL）和锚定DIP脂质体（ODL）在光照、分散介质、生物流体、长期储存条件下的稳定性。采用反相高效液相色谱法研究了大鼠静脉注射DIP注射液、PDL和ODL后血浆中DIP的浓度及其药代动力学行为。药代动力学参数由软件3p97程序计算得出。结果表明，与PDL相比，ODL在体外能提高DIP的稳定性。静脉注射DIP注射液、PDL和ODL后DIP的血浆浓度-时间曲线均符合开放二室模型。DIP注射液、PDL和ODL在大鼠体内的药代动力学参数有显著差异。目前的研究结果表明，与普通脂质体相比，锚定脂质体在体外能提高DIP的稳定性。此外，药代动力学特征的差异归因于锚定脂质体的靶向性。
