OPTIMIZATION STUDY OF DOXORUBICIN LIPOSOMAL PREPARATIONS COATED WITH LAMININ FRAGMENTS

ABSTRACT

Immunoliposomes, coated with two peptide sequences and loaded with doxorubicin, were prepared. The influence of different parameters in the sequential steps of liposomal preparations was studied as, for instance, lipid composition, size reduction methods, elimination of non-entrapped drug, and peptide coating sequence.

Results were evaluated, such as entrapment efficiency, phospholipid/drug and phospholipid/peptide relationship, and size of final preparations. Effective size reduction was only achieved through probe sonication and the presence of peptides on the surface of liposomes, which does not modify, significantly, the final phospholipid/drug relationship, related to the initial values; however, they promoted a slight increase in the size of final preparations. Dialysis was the most suitable method to wash liposomes from reactants, drug and peptides, as well as being the cleanest process to avoid microbial contamination without significant dilution. Peptide coating yields were similar for liposomal compositions presenting free carboxyl groups on the surface. As determined by other authors, the presence of polyethylene glycol monomethoxy chains on the surface reduces the reactivity of NPGE carboxylic groups.

ACKNOWLEDGMENTS

The technical assistance of Maria Osuna is greatly acknowledged. This work has been financed by a grant SAF-97-0174 from the Ministerio de Educación y Cultura, and a FEDER-FD-97-0129. One of us was recipient of a grant from the Ministerio de Ciencia y Tecnología.