Stability and pharmacokinetic studies of O-palmitoyl amylopectin anchored dipyridamole liposomes

• Published in: International journal of pharmaceutics 2006-04, Vol.313 (1), p.136-143
• Main Authors: Cheng, Ji, Zhu, Jia-bi, Wen, Na, Xiong, Fei
• Format: Article
• Language: English
• Subjects: Amylopectin - analogs & derivatives; Amylopectin - chemistry; Animals; Biological and medical sciences; Dipyridamole; Dipyridamole - administration & dosage; Dipyridamole - chemistry; Dipyridamole - pharmacokinetics; Drug Stability; General pharmacology; Injections, Intravenous; Liposomes; Male; Medical sciences; Models, Biological; O-Palmitoyl amylopectin; Palmitates - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Solubility; Stabilization; Surface Properties; Ultraviolet Rays
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.01.031

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.