Recent Developments and Limitations of Poloxamine-Coated Long-Circulating Particles in Experimental Drug Delivery

Abstract

There has been growing interest in the engineering of colloidal carrier systems that upon intravenous administration avoid rapid recognition by scavenger cells of the reticuloendothelial system and adequately remain in the blood. There are several reasons as to why the search for such ‘phagocyte-resistant’ or long-circulating particles is so extensive. First, long-circulating drug carriers may act as a’ sustained release system’ in the blood and slowly discharge their entrapped materials for better treatment and diagnosis. Secondly, long-circulating drug carriers may passively accumulate in pathological sites with affected vasculature (e.g., selected tumours, rheumatoid arthritis, infections) and improve or enhance treatment or diagnosis in those areas (Bakker-Woudenberg et al., 1993; Wu et al., 1993; Huang et al., 1994; Yuan et al., 1994). Thirdly, grafting or covalent attachment of homing molecules such as antibodies, peptides that mimic ligands for αvβ3 and αvβ5 integrins, oligosaccharides that mimic ligands for P-selectin (e.g., synthetic sialyl-Lewis X and small heparin chains containing four or more monosaccharide residues), folate, etc. to long-circulating carries can dramatically improve the targeting precision to sites beyond the reticuloendothelial system (e.g., vascular and tumour endothelial cells, circulating blood cells, circulating toxic materials) (Mulligan et al., 1993; Nelson et al., 1993; Lee and Low, 1994; Bloemen et al., 1995; Gabizon, 1995; Moghimi, 1995a, c; Torchilin, 1995; Lee and Huang, 1996; Huang et al., 1997; Pasqualini et al., 1997).