A novel formulation of VIP in sterically stabilized micelles amplifies vasodilation in vivo

Purpose. To determine whether human vasoactive intestinal peptide (VIP)-pol y(ethylene glycol) (PEG)-grafted distearoyl-phosphatidylethanolamine (DSPE) micelles elicit potent and stable vasodilation in vivo. Methods. PEG-DSPE micelles were prepared by co-precipitation. VIP was loade d into micelles by incubation at room temperature. Vasoactivity of VIP in S SM was determined by monitoring changes in diameter of resistance arteriole s in the in situ hamster cheek pouch using intravital microscopy. Results. VIP easily undergoes self-assembly into small PEG-DSPE micelles (m ean [+/-SEM] size, 18 +/- 1 nm) in a time-dependent fashion. This generates a potent vasoactive matrix at nanomole concentrations of VIP as manifested by similar to 3-fold potentiation and prolongation of vasodilation relativ e to that evoked by aqueous VIP alone (p < 0.05). This response is specific and mediated by the L-arginine/nitric oxide (NO) biosynthetic pathway. Mic ellar VIP dispersion remains vasoactive for at least 14 days after preparat ion and storage at 4 degrees C. Conclusions. A novel, self-associated, small and stable PEG-DSPE micellar f ormulation of VIP amplifies vasodilation in the in situ peripheral microcir culation in a specific fashion by elaborating NO. An optimized formulation could be considered for certain cardiovascular disorders associated with L- arginine/NO biosynthetic pathway dysfunction.