A Novel Formulation of VIP in Sterically Stabilized Micelles Amplifies Vasodilation In Vivo

Purpose. To determine whether human vasoactive intestinal peptide (VlP)-poly(ethylene glycol) (PEG)-grafted distearoyl-phosphatidyleth-anolamine (DSPE) micelles elicit potent and stable vasodilation in vivo.Methods. PEG-DSPE micelles were prepared by co-precipitation. VIP was loaded into micelles by incubation at room temperature. Vasoactivity of VIP in SSM was determined by monitoring changes in diameter of resistance arterioles in the in situ hamster cheek pouch using intravital microscopy.Results. VIP easily undergoes self-assembly into small PEG-DSPE micelles (mean [±SEM] size, 18 ± 1 nm) in a time-dependent fashion. This generates a potent vasoactive matrix at nanomole concentrations of VIP as manifested by ~3-fold potentiation and prolongation of vasodilation relative 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. Micellar VIP dispersion remains vasoactive for at least 14 days after preparation and storage at 4°C.Conclusions. A novel, self-associated, small and stable PEG-DSPE micellar formulation of VIP amplifies vasodilation in the in situ peripheral microcirculation 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.