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 (AUC 0‐∞) 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 AUC 0‐∞ 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.