Polysialic acid-based micelles for encapsulation of hydrophobic drugs

Abstract

Despite improvements relative to unmodified counterparts, poly(ethylene glycol) (PEG) conjugation may not be the ideal solution for improving circulatory stability of current nanoparticle carriers or free drugs. Polysialic acid (PSA), a natural polymer for which the body possesses no receptors, has been conjugated directly to biologically active molecules to prevent premature clearance; however, this concept has not yet been applied to nanoparticle drug carrier systems. In the current study, PSA was modified with a long-chain hydrocarbon through reaction of the carboxylic acid side groups with N-decylamine (DA). The resultant PSA-DA conjugates self-assembled into micelles for encapsulation of hydrophobic drug molecules, as demonstrated with Cyclosporine A. Cytotoxicty was dependent on the degree of substitution with DA. On the basis of size and zeta potential, the micelles are capable of passively targeting diseased regions, such as cancer and inflammatory tissue. Further investigations are necessary to explore whether the PSA-based micelles possess stealth properties similar to those of PEG and to establish in vitro and in vivo efficacy.