title: Novel, biocompatible, and disease modifying VIP nanomedicine for rheumatoid arthritis.
abstract: Despite advances in rheumatoid arthritis (RA) treatment, efficacious and safe disease-modifying therapy still represents an unmet medical need. Here, we describe an innovative strategy to treat RA by targeting low doses of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized micelles (SSMs). This spontaneous interaction of VIP with SSM protects the peptide from degradation or inactivation in biological fluids and prolongs circulation half-life. Treatment with targeted low doses of nanosized SSM-VIP but not free VIP in buffer significantly reduced the incidence and severity of arthritis in an experimental model, completely abrogating joint swelling and destruction of cartilage and bone. In addition, SSM associated VIP, unlike free VIP, had no side-effects on the systemic functions due to selective targeting to inflamed joints. Finally, low doses of VIP in SSM successfully downregulated both inflammatory and autoimmune components of RA. Collectively, our data clearly indicate that VIP-SSM should be developed to be used as a novel nanomedicine for the treatment of RA.
authors.affiliation: Department of Biopharmaceutical Sciences, Jesse Brown VA Medical Center, Chicago, Illinois 60612, United States.
authors.forename: Varun
authors.initials: V
authors.lastname: Sethi
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Antonina
authors.initials: A
authors.lastname: Kuzmis
authors.forename: Helen
authors.initials: H
authors.lastname: Kastrissios
authors.forename: James
authors.initials: J
authors.lastname: Artwohl
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyuksel
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008823:Micelles; D050997:Nanomedicine; D010743:Phospholipids / Q000737:chemistry; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D008823:Micelles; D010743:Phospholipids; D014660:Vasoactive Intestinal Peptide