Application of drug-containing liposomes to the duration of the intramuscular absorption of water-soluble drugs in rats

An attempt was made to use liposomes as a carrier intended for prolonged intramuscular absorption of highly water-soluble drugs. 131I-Insulin, 14C-sucrose, 14C-inulin, and 14C-cefazolin sodium, a new derivative of cepharosporin antibiotics, were chosen as model compounds. These model drugs were dissolved in pH 7.0 buffer solution and entrapped in liposomes composed of various ratios of phosphatidyl choline, cholesterol, and dicetylphosphate. After injection in the form of such liposomal suspensions, clearance of model drugs from the intramuscular injection site was delayed to a considerable extent in comparison with the control aqueous buffer injections. It was observed that the larger the amount of cholesterol incorporation into liposomes were, the slower the drug absorption became. Although the intramuscular absorption of the drugs from the rat thigh muscle was delayed by their entrapment in liposomes, extent of the prolongation was less than that expected from their in vitro release characteristics determined by dialysis experiments. Physical stability of liposomes containing 14C-cefazolin sodium was tested in the presence of serum and muscle homogenate. It appears that liposomes are gradually hydrolysed or affected by serum thereby losing their integrity and releasing the entrapped drugs.