LYMPH-NODE TARGETING AND PHARMACOKINETICS OF [H-3] METHOTREXATE-ENCAPSULATED NEUTRAL LARGE UNILAMELLAR VESICLES AND IMMUNOLIPOSOMES

The lymph node targeting ability and the pharmacokinetics of [H-3]meth otrexate (MTX)-bearing neutral large unilamellar vesicles (NLUV) and i mmunoliposomes (IL; anti-rat immunoglobulin G-conjugated liposomes) we re compared with those of free [H-3]MTX after intravenous (i.v.) or in tramuscular (i.m.) injection to rats. The plasma radioactivity decline d slowly after iv. injection of the NLUV or IL when compared with that after [H-3]MTX, and might be due to the slow release of radioactivity from the NLUV or IL which are present in plasma and/or taken up into tissues. The values of AUC0-24 h in the regional lymph nodes were 6.60 - and 6.66-fold increased after i.m. injection of NLUV and IL, respect ively, when compared with the value after free [H-3]MTX, and the corre sponding values for nonregional lymph nodes were 5.35- and 4.78-fold. It strongly suggested that the NLUV or IL could have a better lymph ta rgeting ability than that of free [H-3]MTX. The encapsulation efficien cy of [H-3]MTX in the NLUV increased with increasing cholesterol conte nts up to 44 mol% and decreased thereafter as prepared by the reverse phase evaporation method. The in vitro release of radioactivity was re duced when the NLUV or IL was incubated in plasma kept at 37-degrees-C and at a rate of 50 oscillations/min (opm) when compared with the val ue from [H-3]MTX using a dialysis bag.