Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes.
A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.
School of Pharmaceutical Sciences, University of Science, Malaysia, Penang, Malaysia.
Sharon Sheue Nee
SS
Ling
Enrico
E
Magosso
Nurzalina Abdul Karim
NA
Khan
Kah Hay
KH
Yuen
Susan Anne
SA
Barker
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002439:Cefotaxime / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D008081:Liposomes; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D002439:Cefotaxime