Human VIP-alpha: a long-acting, biocompatible and biodegradable peptide nanomedicine for essential hypertension.
We have previously shown that self-association of human vasoactive intestinal peptide with sterically stabilized liposomes (VIP-alpha) alters peptide conformation from random coil in aqueous solution to alpha-helix. This, in turn, protects the peptide from hydrolysis and amplifies and prolongs its bioactivity. The purpose of this study was to determine whether a single, intravenous injection of low-dose human VIP-alpha normalizes systemic arterial pressure in anesthetized spontaneously hypertensive hamsters for a prolonged period of time in a selective fashion. We found that intravenous injection of human VIP-alpha, VIP alone (each, 1.0 nmol) and empty liposomes had no significant effects on mean arterial pressure (MAP) in normotensive hamsters. By contrast, human VIP-alpha (0.01-1.0 nmol) evoked a significant concentration-dependent decrease in MAP to the normative range in spontaneously hypertensive hamsters that lasted throughout the observation period (6 h; p<0.05). VIP alone and empty liposomes had no significant effects on MAP in these animals. We conclude that a single, low-dose intravenous injection of human VIP-alpha normalizes systemic arterial pressure in spontaneously hypertensive hamsters for a prolonged period of time in a selective fashion. We suggest that human VIP-alpha should be further developed as a long-acting, biocompatible and biodegradable peptide nanomedicine for essential hypertension.
Onyüksel
Hayat
H
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, IL 60612, United States.
Séjourné
Florence
F
Suzuki
Hideyuki
H
Rubinstein
Israel
I
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D001673:Biodegradation, Environmental; D006224:Cricetinae; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D049329:Nanostructures / Q000737:chemistry; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001672:Biocompatible Materials; D014660:Vasoactive Intestinal Peptide