Folate receptor-targeted liposomes as vectors for therapeutic agents.

The folate receptor is a cell surface protein that has recently been identified as a tumor marker, due to its differential overexpression in several malignancies. Current research indicates that folate can be covalently attached to the surface of liposomes to mediate their selective internalization by tumor cells through the folate receptor-mediated endocytic pathway. Optimized liposome formulations, characterized by improvements in drug loading, extended residence times in the circulation and improved drug release, have been developed to improve the biodistribution of therapeutic molecules.

Incorporation of reversibly cross-linked polyplexes into LPDII vectors for gene delivery.

LPDII vectors are synthetic vehicles for gene delivery composed of polycation-condensed DNA complexed with anionic liposomes. In this study, we evaluated the stability and transfection properties of polyethylenimine (PEI, 25 kDa)/DNA polyplexes before and after covalent cross-linking with dithiobis(succinimidylpropionate) (DSP) or dimethyl x 3,3'-dithiobispropionimidate x 2HCl (DTBP), either alone or as a component of LPDII vectors. We found that cross-linking PEI/DNA polyplexes at molar ratios > or =10:1 (DSP or DTBP:PEI) stabilized these complexes against polyanion disruption, and that this effect was reversible by reduction with 20 mM dithioerythritol (DTE).

Characterization of a novel diolein-based LPDII vector for gene delivery.

LPDII vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA (polyplexes) complexed with anionic pH-sensitive liposomes. Here, we describe a novel LPDII formulation containing polyethylenimine (PEI) polyplexes complexed with anionic pH-sensitive liposomes composed of diolein/cholesteryl hemisuccinate (CHEMS) (6:4 mol/mol). The pH-sensitivity of diolein/CHEMS liposomes was evaluated through quantitative fluorescence measurements of calcein release and particle size analysis.