In vivo and in vitro assessment of baseline blood-brain barrier parameters in the presence of novel nanoparticles

被引:78
作者
Lockman, PR
Koziara, J
Roder, KE
Paulson, J
Abbruscato, TJ
Mumper, RJ
Allen, DD
机构
[1] Texas Tech Univ HSC, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA
[2] Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40536 USA
关键词
cerebral perfusion flow; drug delivery; integrity; polybutylcyanoacrylate; permeability;
D O I
10.1023/A:1023492015851
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. Nanoparticles have advantage as CNS drug delivery vehicles given they disguise drug permeation limiting characteristics. Conflicting toxicological data, however, is published with regard to blood-brain barrier integrity and gross mortality. Methods. To address this issue two novel nanoparticle types: "emulsifying wax/Brij 78" and "Brij 72/Tween 80 nanoparticles were evaluated in vivo for effect on cerebral perfusion flow, barrier integrity, and permeability using the in situ brain perfusion technique. Additional evaluation was completed in vitro using bovine brain microvessel endothelial cells for effect on integrity, permeability, cationic transport interactions, and tight junction protein expression. Results. In the presence of either nanoparticle formulation, no overall significant differences were observed for cerebral perfusion flow in vivo. Furthermore, observed in vitro and in vivo data showed no statistical changes in barrier integrity, membrane permeability, or facilitated choline transport. Western blot analyses of occludin and claudin-1 confirmed no protein expression changes with incubation of either nanoparticle. Conclusions. The nanoparticle formulations appear to have no effect on primary BBB parameters in established in vitro and in vivo blood-brain barrier models.
引用
收藏
页码:705 / 713
页数:9
相关论文
共 30 条
  • [1] Abbruscato TJ, 1999, J PHARMACOL EXP THER, V289, P668
  • [2] Abbruscato TJ, 1996, J PHARMACOL EXP THER, V276, P1049
  • [3] Characterization of the blood-brain barrier choline transporter using the in situ rat brain perfusion technique
    Allen, DD
    Smith, QR
    [J]. JOURNAL OF NEUROCHEMISTRY, 2001, 76 (04) : 1032 - 1041
  • [4] ALLEN DD, 1997, PHARMACOL RES S, V14, P337
  • [5] Interaction of poly(butylcyanoacrylate) nanoparticles with the blood-brain barrier in vivo and in vitro
    Alyaudtin, RN
    Reichel, A
    Löbenberg, R
    Ramge, P
    Kreuter, J
    Begley, DJ
    [J]. JOURNAL OF DRUG TARGETING, 2001, 9 (03) : 209 - +
  • [6] BOVINE BRAIN MICROVESSEL ENDOTHELIAL-CELL MONOLAYERS AS A MODEL SYSTEM FOR THE BLOOD-BRAIN-BARRIER
    AUDUS, KL
    BORCHARDT, RT
    [J]. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 507 : 9 - 18
  • [7] CHARACTERIZATION OF AN INVITRO BLOOD-BRAIN-BARRIER MODEL SYSTEM FOR STUDYING DRUG TRANSPORT AND METABOLISM
    AUDUS, KL
    BORCHARDT, RT
    [J]. PHARMACEUTICAL RESEARCH, 1986, 3 (02) : 81 - 87
  • [8] BICKEL U, 1998, INTRO BLOOD BRAIN BA, P4
  • [9] Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines
    Blum, MS
    Toninelli, E
    Anderson, JM
    Balda, MS
    Zhou, JY
    O'Donnell, L
    Pardi, R
    Bender, JR
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1997, 273 (01): : H286 - H294
  • [10] ELECTRICAL-RESISTANCE ACROSS THE BLOOD-BRAIN-BARRIER IN ANESTHETIZED RATS - A DEVELOPMENTAL-STUDY
    BUTT, AM
    JONES, HC
    ABBOTT, NJ
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1990, 429 : 47 - 62