期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 100, 期 3, 页码 1045-1056出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.22342
关键词
ligand density; poly(DL-lactic-co-glycolic acid) nanoparticles; cLABL; Pluronic (R); binding and cellular uptake
资金
- Cystic Fibrosis Foundation
- Coulter Foundation
- Higuchi Biosciences Center
- American Heart Association
- NIH [R01-AI-063002, R03 AR054035, P20 RR016443, T32 GM08359-20]
- Department of Defense
- NSF [CHE 0719464]
During infection, pathogens utilize surface receptors to gain entry into intracellular compartments. Multiple receptor-ligand interactions that lead to pathogen internalization have been identified and the importance of multivalent ligand binding as a means to facilitate internalization has emerged. The effect of ligand density, however, is less well known. In this study, ligand density was examined using poly(DL-lactic-co-glycolic acid) nanoparticles (PLGA NPs). A cyclic peptide, cLABL, was used as a targeting moiety, as it is a known hgand for intercellular cell adhesion molecule-1 (ICAM-1). To modulate the number of reactive sites on the surface of PLGA NPs, modified Pluronic (R) with carboxyl groups and Pluronic (R) with hydroxyl groups were combined in different ratios and the particle properties were examined. Utilizing a surfactant mixture directly affected the particle charge and the number of reactive sites for cLABL conjugation. The surface density of cLABL peptide increased as the relative amount of reactive Pluronic (R) was increased. Studies using carcinomic human alveolar basal epithelial cells (A549) showed that cLABL density might be optimized to improve cellular uptake. These results complement other studies, suggesting that surface density of the targeting moiety on the NP surface should be considered to enhance the effect of hgands used for cell targeting. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1045-1056, 2011
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