Novel, Biocompatible, and Disease Modifying VIP Nanomedicine for Rheumatoid Arthritis

被引：45
|
作者：
Sethi, Varun [1 ]
Rubinstein, Israel [2 ,5 ]
Kuzmis, Antonina [1 ]
Kastrissios, Helen [1 ]
Artwohl, James [4 ]
Onyuksel, Hayat [1 ,3 ]
机构：
[1] Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Med, Chicago, IL 60612 USA
[3] Univ Illinois, Dept Bioengn, Chicago, IL 60612 USA
[4] Univ Illinois, Dept Biol Resources Lab, Chicago, IL 60612 USA
[5] Jesse Brown VA Med Ctr, Chicago, IL 60612 USA
来源：
MOLECULAR PHARMACEUTICS | 2013年 / 10卷 / 02期
关键词：
inflammation; autoimmune disorders; phospholipids; micelles; nanomedicine; vasoactive intestinal peptide; VASOACTIVE-INTESTINAL-PEPTIDE; COLLAGEN-INDUCED ARTHRITIS; PHOSPHOLIPID MICELLES; INFLAMMATORY-DISEASES; GAMMA-CAMERA; TH17; CELLS; IN-VIVO; AUTOIMMUNE; ALPHA; PATHOGENESIS;
D O I：
10.1021/mp300539f
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
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.
引用
收藏
页码：728 / 738
页数：11
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