Polysialic acid (PSA) has been identified as a natural, hydrophilic
polymer that can be used to extend circulation time and improve therapeutic efficacy when used as the basis of
drug carrier systems. Here, to further investigate the potential of PSA to alter the pharmacokinetic and pharmacodynamic profiles of associated
therapeutics, PSA-based
micelles were formed via self-assembly of PSA grafted with
polycaprolactone (PCL) at a critical
micelle concentration of 84.7±13.2 μg/ml.
Cyclosporine A (CyA), a therapeutic used in the treatment of
rheumatoid arthritis, was loaded into the PSA-PCL
micelles with a loading capacity and loading efficiency of 0.09±0.02 mg CyA/mg PSA-PCL and 29.3±6.4%, respectively. CyA loading resulted in a size increase from 73.8±12.4 nm to 107.5±9.3 nm at 25 °C and from 138.4±40.7 nm to 195.3±52.1 nm at 37 °C, favorable size ranges for
drug delivery to inflamed tissue characterized by leaky vasculature, as occurs during
rheumatoid arthritis pathogenesis. As an
indicator of the stealth nature the
micelles are expected to exhibit in vivo, the fixed aqueous layer thickness of the PSA-PCL
micelles was determined to be 0.63±0.02 nm, comparable to that obtained for traditionally utilized poly(
ethylene glycol) coated
liposomes. The PSA-PCL
micelles had a negligible effect on the viability of the SW982 synovial fibroblast cell line. Fluorescent microscopy was utilized to demonstrate uptake by the synovial fibroblasts through a non-receptor mediated form of endocytosis and partitioning of CyA into the membrane.