Nanoemulsions of an anti-oxidant synergy formulation containing gamma tocopherol have enhanced bioavailability and anti-inflammatory properties

被引:49
作者
Kuo, Fonghsu [1 ]
Subramanian, Balajikarthick [1 ]
Kotyla, Timothy [1 ]
Wilson, Thomas A. [1 ]
Yoganathan, Subbiah [2 ]
Nicolosi, Robert J. [1 ]
机构
[1] Univ Massachusetts Lowell, Ctr Hlth & Dis Res, Div NanoMed, Biomed Engn & Biotechnol PhD Program, Lowell, MA 01854 USA
[2] Forsyth Inst, Boston, MA 02115 USA
关键词
MicroFluidizer Processor (R)-based nanoemulsions; Anti-oxidant synergy formulation; Croton oil; Tocopherol;
D O I
10.1016/j.ijpharm.2008.07.022
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study investigated whether MicroFluidizer Processor (R)-based nanoemulsions of an antioxidant synergy formulation (ASF), containing delta, alpha and gamma tocopherol influenced inflammation and bioavailability in CD-1 mice. Croton oil was applied to all animals' right ear lobe to induce inflammation. Auricular thickness was measured after 2 and 6 h after the various treatments. The animal plasma and ear lobes were collected and frozen for bioavailability and cytokine analyses. The ASF nanoemulsions of alpha,delta, orgamma tocopherol significantly reduced auricular thickness compared to control (57, -57, and -71%, respectively) and blank nanoemulsion (-50, -50, -67%, respectively). Relative to the suspensions of ASF, only the nanoemulsion of ASF containing gamma tocopherol significantly reduced auricular thickness (-60%). whereas the 40% reduction with nanoemulsions of delta tocopherol compared to suspension was not statistically significant. Auricular concentrations of cytokines TNF-alpha and IL-1 alpha were significantly reduced in mice treated only with ASF nanoemulsions of gamma tocopherol compared to control (-53, -46%, respectively) and blank nanoemulsion (-52, -46%, respectively). Auricular thickness was significantly associated with tissue TNF-alpha (r=0.539, p < 0.001) and IL-1 alpha concentrations (r=0.404, p=0.01). Bioavailability for gamma and delta was dramatically enhanced (2.2- and 2.4-folds) with the nanoemulsion compared to suspensions. Only the plasma gamma tocopherol concentration was significantly associated with auricular thickness (r=-0.643, P=0.001). In conclusion, nanoemulsions of ASF containing gamma, alpha, and delta tocopherol, have enhanced anti-inflammatory properties and increased bioavailability, with gamma tocopherol, in particular compared to their suspensions. (c) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:206 / 213
页数:8
相关论文
共 41 条
[1]  
AMY LH, 2003, NEUROSCI RES COMMUN, V33, P73
[2]   VITAMIN-E ACTIVITY OF GAMMA-TOCOPHEROL IN RAT, CHICK AND HAMSTER [J].
BIERI, JG ;
EVARTS, RP .
JOURNAL OF NUTRITION, 1974, 104 (07) :850-857
[3]   gamma-Tocopherol traps mutagenic electrophiles such as NOx and complements alpha-tocopherol: Physiological implications [J].
Christen, S ;
Woodall, AA ;
Shigenaga, MK ;
SouthwellKeely, PT ;
Duncan, MW ;
Ames, BN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (07) :3217-3222
[4]   Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel [J].
Constantinides, PP ;
Lambert, KJ ;
Tustian, AK ;
Schneider, B ;
Lalji, S ;
Ma, WW ;
Wentzel, B ;
Kessler, D ;
Worah, D ;
Quay, SC .
PHARMACEUTICAL RESEARCH, 2000, 17 (02) :175-182
[5]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867
[6]   Tumor necrosis factor-α antagonists for the treatment of rheumatic diseases [J].
Criscione, LG ;
St Clair, EW .
CURRENT OPINION IN RHEUMATOLOGY, 2002, 14 (03) :204-211
[7]  
DESAI A, 2007, J PHARM SCI
[8]  
Ghosh PK, 2006, AAPS PHARMSCITECH, V7
[9]   ORAL ALPHA-TOCOPHEROL SUPPLEMENTS DECREASE PLASMA GAMMA-TOCOPHEROL LEVELS IN HUMANS [J].
HANDELMAN, GJ ;
MACHLIN, LJ ;
FITCH, K ;
WEITER, JJ ;
DRATZ, EA .
JOURNAL OF NUTRITION, 1985, 115 (06) :807-813
[10]  
Jiang Q, 2001, AM J CLIN NUTR, V74, P714