The absorption behavior of cyclosporin A lecithin vesicles in rat intestinal tissue.
The purpose of the study was to investigate the absorption behavior of lecithin vesicles of cyclosporin A (CsA-VES), prepared by the rotary evaporation method and treated further with sonication. The everted gut sac technique and in situ circulation method were used to examine: (1) relationship between the CsA-VES absorption velocity and the CsA-VES content; (2) the influence of the intestinal mucus, blank vesicles, concentration of Na(+), energy inhibitor and P-gp inhibitor on the absorption of CsA-VES; and (3) the respective accumulated content of CsA in the incubating medium and the sacs after incubation with Sandimmum Neoral((R))(CsA-NEO) and CsA-VES. Our results showed there was a saturated absorption of CsA. Most CsA-VES accumulated in the mucus before it reached the intestinal tissue. There was no significant difference in the accumulated absorption content in the incubating medium and the sacs of CsA-NEO and CsA-VES. The addition of blank vesicles and concentration of Na(+) had no significant influence on the accumulated absorption of CsA (P>0.05). The energy inhibitor and P-gp inhibitor influenced the accumulated absorption of CsA significantly (P<0.05). CsA-VES may be transported by phagocytosis. Mucus was a barrier blocking the diffusion of CsA-VES. CsA-NEO and CsA-VES showed equal absorption levels in the intestine.
Chen
Ying
Y
Department of Pharmaceutics, China Pharmaceutical University, 21009, Nanjing, PR China.
Ping
Qineng
Q
Guo
Jianxin
J
Lv
Wenli
W
Gao
Jing
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D009994:Osmolar Concentration; D010713:Phosphatidylcholines; D051381:Rats; D013810:Therapeutic Equivalency
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D010713:Phosphatidylcholines; D016572:Cyclosporine