Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats

Objectives A liposome preparation that is amenable to receptor-mediated endocytosis has been developed to enhance the oral bioavailability of poorly absorbable peptidomimetic drugs by use of folic acid as the mediator of liposomal uptake. Methods Folic acid was physically coupled to the surface of the liposomes and cefotaxime was used as the model drug. In-vivo evaluation was carried out on eight Sprague-Dawley rats in a two-way crossover study to compare the oral bioavailability of cefotaxime loaded in folic acid-free liposomes and folic acid-coupled liposomes. Blood samples were collected from the tail vein and plasma cefotaxime levels were determined using an HPLC method. Key findings Enhanced oral bioavailability (AUC0-{infinity}) of cefotaxime was observed when administered via folic acid-coupled liposomes. The peak plasma concentration (Cmax) of cefotaxime was increased when administered via folic acid-coupled liposomes as compared with folic acid-free liposomes. At 90% confidence interval, the value for AUC0-{infinity} was 1.4-2-times higher and the value for Cmax was 1.2-1.8-times higher for the folic acid-coupled liposomes compared with folic acid-free liposomes. Conclusions Folic acid could enhance the uptake of liposomally entrapped drug. It could be a useful candidate to supplement liposome delivery systems.