期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 37, 期 2, 页码 141-150出版社
ELSEVIER
DOI: 10.1016/j.ejps.2009.02.008
关键词
ICAM-1; Peptide; PLGA; Nanoparticles; Targeting
资金
- Royal Thai Government
- Cystic Fibrosis Foundation
- Coulter Foundation
- Higuchi Biosciences Center
- American Heart Association
- NIH [1103 AR054035, P20 RR016443, T32 GM08359-11]
- Department of Defense
- NSF [CHE 0719464]
Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading. and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been identified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to [CAM-1. In addition. cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic (R) surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1-mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-I using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system. Published by Elsevier B.V.
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