A NOVEL PEPTIDE-GRAFTED LIPOSOMAL DELIVERY SYSTEM TARGETED TO MACROPHAGES

The interaction of chemotactic peptide (e.g., fMet-Leu-Phe)-grafted li posomes with macrophages is noted to be rapid and specific. At a graft ed peptide concentration of 100 nmol, internalization of the peptide-g rafted liposomes by the macrophages is found to reach equilibrium in 3 0 min. The peptide alone and the peptide-grafted empty liposomes are f ound to show moderate antileishmanial activity in vitro. Primaquine, w hich is known to generate O-2(-) in phagocytic cells, showed leishmani cidal properties when it was tested in vitro against parasite-infected macrophages over a certain range of concentrations. It showed much be tter efficacy against experimental leishmaniasis when it was used in t he fMet-Leu-Phe-grafted liposomal form in comparison with its efficacy when it was either in the free form or encapsulated in ungrafted lipo somes. The conventional toxicity parameters (e.g., blood pathology and tissue histology-specific enzyme levels related to normal liver funct ion) are found to be very close to normal when fMet-Leu-Phe-grafted li posomal primaquine is used. The biodegradabilities of both the drug an d the delivery systems are also found to be very satisfactory, Thus, t his delivery system may have possible applications for the treatment o f leishmaniasis as well as other macrophage-associated disorders.