title: Micellar nanomedicine of human neuropeptide Y.
abstract: Human neuropeptide Y (NPY) is an important biologics that regulates a multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (within minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and biodegradable sterically stabilized phospholipid micelles (SSM) improves its stability and bioactivity. We found that in saline NPY spontaneously aggregates; however, in the presence of SSM it self-associates with the micelles as monomers. Three NPY molecules self-associate with 1 SSM at saturation. This process stabilizes the peptide in α-helix conformation, abrogates its degradation by dipeptidyl peptidase-4 and potentiates NPY-induced inhibition of cAMP elaboration in SK-N-MC cells. Collectively, these data indicate that self-association of NPY with SSM stabilizes and protects the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro. We propose further development of NPY in SSM as a novel, long-acting nanomedicine.
  
  
  BACKGROUND
  Human neuropeptide Y (NPY) regulates a multitude of physiological functions and could be amenable to therapeutic manipulations, which is currently limited by its short half life. Self-association of NPY with spherically stabilized micelles (SSM) protects and stabilizes the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro, enabling future therapeutic considerations.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Antonina
authors.initials: A
authors.lastname: Kuzmis
authors.forename: Sok Bee
authors.initials: SB
authors.lastname: Lim
authors.forename: Esha
authors.initials: E
authors.lastname: Desai
authors.forename: Eunjung
authors.initials: E
authors.lastname: Jeon
authors.forename: Bao-Shiang
authors.initials: BS
authors.lastname: Lee
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*; D009478:Neuropeptide Y / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry
chemical_list: D008823:Micelles; D009478:Neuropeptide Y; D010743:Phospholipids; D000242:Cyclic AMP; D018819:Dipeptidyl Peptidase 4