Intramuscular absorption and regional lymphatic uptake of liposome-entrapped inulin

Abstract

An investigation of the effects of the liposome variables (size, surface area, and amount of injected lipid) on the intramuscular absorption and subsequent lymphatic uptake of drug from the injection site (left muscle) and in the opposite (right) muscle and lymph node was done in mice. Two size ranges were studied (0.3-2.0 mu and 0.15-0.7 mu). Large multilamellar vesicles were studied at lipid doses of 20.7 and 9.0 mg/kg, whereas small multilamellar vesicles were investigated at a dose of 9.5 mg/kg. Liposomes were composed of phosphatidylcholine/cholesterol/phosphatidylserine/alpha-tocopherol/14C-dipalmitoylphosphatidylcholine (as a marker for the lipid phase), 4:5:1:0.01:0.01 (molar ratio). 3H-inulin was used to monitor the aqueous phase. At 24 hr after administration, large liposomes tended to result in the largest fraction of drug at the injection site, with the 3H/14C ratio indicating stability of the remaining vesicles. Small liposomes showed a greater uptake of inulin via the lymphatics. Decreasing the total amount of injected lipid resulted in a slower absorption of large liposomes and a greater uptake via the lymphatics.