Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury

被引:186
作者
Kim, Young-tae
Caldwell, Jon-Michael
Bellamkonda, Ravi V.
机构
[1] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Lab Neuroengn, Atlanta, GA 30332 USA
[2] Emory Univ, Atlanta, GA 30332 USA
关键词
Nerve regeneration; Inflammation; Hydrogel; Drug delivery; CONTROLLED-TRIAL; EXPRESSION; MICROGLIA; REPAIR; BRAIN; MODEL; RATS;
D O I
10.1016/j.biomaterials.2008.12.077
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Systemic administration of a high-dose of Methylprednisolone (MP) can reduce neurological deficits after acute spinal cord injury (SCI). However, the use of high-dose MP in treating acute SO is controversial due to significant dose related side effects and relatively modest improvements in neurological function. Here, using a rat model of SCI, we compare the efficacy of controlled, nanoparticle-enabled local delivery of MP to the injured spinal cord with systemic delivery of MP, and a single local injection of MP without nanoparticles. Based on histological and behavioral data, we report that local, sustained delivery of MP via nanoparticles is significantly more effective than systemic delivery. Relative to systemic delivery, MP-nanoparticle therapy significantly reduced lesion volume and improved behavioral outcomes. Nanoparticle-enabled delivery of MP presents an effective method for introducing MP locally after SO and significantly enhances therapeutic effectiveness compared to bare MP administered either systemically or locally. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2582 / 2590
页数:9
相关论文
共 28 条
[1]   INFLUENCE OF ROUTE OF ADMINISTRATION ON THE PHARMACOKINETICS OF METHYLPREDNISOLONE [J].
ANTAL, EJ ;
WRIGHT, CE ;
GILLESPIE, WR ;
ALBERT, KS .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1983, 11 (06) :561-576
[2]   A new mechanism of methylprednisolone and other corticosteroids action demonstrated in vitro: Inhibition of a proteinase (calpain) prevents myelin and cytoskeletal protein degradation [J].
Banik, NL ;
Matzelle, D ;
Terry, E ;
Hogan, EL .
BRAIN RESEARCH, 1997, 748 (1-2) :205-210
[3]   Pharmacological approaches to repair the injured spinal cord [J].
Baptiste, DC ;
Fehlings, MG .
JOURNAL OF NEUROTRAUMA, 2006, 23 (3-4) :318-334
[4]   Chemiluminescent detection of S-nitrosated proteins:: Comparison of tri-iodide, copper/CO/cysteine, and modified copper/cysteine methods [J].
Basu, Swati ;
Wang, Xunde ;
Gladwin, Mark T. ;
Kim-Shapiro, Daniel B. .
NITRIC OXIDE, PART F: OXIDATIVE AND NITROSATIVE STRESS IN REDOX REGULATION OF CELL SIGNALING, 2008, 440 :137-156
[5]   Restoring function after spinal cord injury [J].
Becker, D ;
Sadowsky, CL ;
McDonald, JW .
NEUROLOGIST, 2003, 9 (01) :1-15
[6]   A RANDOMIZED, CONTROLLED TRIAL OF METHYLPREDNISOLONE OR NALOXONE IN THE TREATMENT OF ACUTE SPINAL-CORD INJURY - RESULTS OF THE 2ND NATIONAL ACUTE SPINAL-CORD INJURY STUDY [J].
BRACKEN, MB ;
SHEPARD, MJ ;
COLLINS, WF ;
HOLFORD, TR ;
YOUNG, W ;
BASKIN, DS ;
EISENBERG, HM ;
FLAMM, E ;
LEOSUMMERS, L ;
MAROON, J ;
MARSHALL, LF ;
PEROT, PL ;
PIEPMEIER, J ;
SONNTAG, VKH ;
WAGNER, FC ;
WILBERGER, JE ;
WINN, HR .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (20) :1405-1411
[7]   Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up - Results of the third National Acute Spinal Cord Injury randomized controlled trial [J].
Bracken, MB ;
Shepard, MJ ;
Holford, TR ;
Leo-Summers, L ;
Aldrich, EF ;
Fazl, M ;
Fehlings, MG ;
Herr, DL ;
Hitchon, PW ;
Marshall, LF ;
Nockels, RP ;
Pascale, V ;
Perot, PL ;
Piepmeier, J ;
Sonntag, VKH ;
Wagner, F ;
Wilberger, JE ;
Winn, HR ;
Young, W .
JOURNAL OF NEUROSURGERY, 1998, 89 (05) :699-706
[8]   A realistic brain tissue phantom for intraparenchymal infusion studies [J].
Chen, ZJ ;
Gillies, GT ;
Broaddus, WC ;
Prabhu, SS ;
Fillmore, H ;
Mitchell, RM ;
Corwin, FD ;
Fatouros, PP .
JOURNAL OF NEUROSURGERY, 2004, 101 (02) :314-322
[9]   Spatial distribution and acute anti-inflammatory effects of Methylprednisolone after sustained local delivery to the contused spinal cord [J].
Chvatal, Stacie A. ;
Kim, Young-Tae ;
Bratt-Leal, Andres M. ;
Lee, Hyunjung ;
Bellamkonda, Ravi V. .
BIOMATERIALS, 2008, 29 (12) :1967-1975
[10]   Consequences of high-dose steroid therapy for acute spinal cord injury [J].
Gerndt, SJ ;
Rodriguez, JL ;
Pawlik, JW ;
Taheri, PA ;
Wahl, WL ;
Micheals, AJ ;
Papadopoulos, SM .
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 1997, 42 (02) :279-282