The in vitro cell association of invasin coated polylactide-co-glycolide nanoparticles

To determine the effect of particle size and ligand surface density on the cellular association of poly lactide-co-glycolide nanoparticles covalently coated with bacterial invasin. Poly lactide-co-glycolide nanoparticles containing a flourescent probe were prepared at four diameters 155 nm, 200 nm,...

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Bibliographic Details
Published in:	Pharmaceutical research 2000-11, Vol.17 (11), p.1420-1425
Main Authors:	DAWSON, Gordon F, HALBERT, Gavin W
Format:	Article
Language:	eng
Subjects:	Adhesins, Bacterial Amino acids Bacterial Proteins - administration & dosage Bacterial Proteins - metabolism Biocompatible Materials - administration & dosage Biocompatible Materials - metabolism Biological and medical sciences Carbocyanines Carrier Proteins - administration & dosage Carrier Proteins - metabolism Cell Line Chromatography Drug Carriers E coli Flow Cytometry Fluorescent Dyes General pharmacology Humans Kinetics Lactic Acid - administration & dosage Lactic Acid - metabolism Ligands Maltose-Binding Proteins Medical sciences Nanoparticles Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Polyglycolic Acid - administration & dosage Polyglycolic Acid - metabolism Polylactic Acid-Polyglycolic Acid Copolymer Polymers - administration & dosage Polymers - metabolism Proteins Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - metabolism
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Summary:	To determine the effect of particle size and ligand surface density on the cellular association of poly lactide-co-glycolide nanoparticles covalently coated with bacterial invasin. Poly lactide-co-glycolide nanoparticles containing a flourescent probe were prepared at four diameters 155 nm, 200 nm, 375 nm and 600 nm using standard techniques. Bacterial invasin was covalently coupled to the particles surface at varying surface concentrations using a water soluble carbodiimide. The modified particle's cellular association with HEp2 2B cells in tissue culture was determined using flow cytometry. Cellular association of modified nanoparticles was time dependent, abolished at low temperature, competitively inhibited by free invasin or the RGD peptide ligand and saturable. Increased cell association was produced by increasing the particle's surface invasin concentration however, this effect was size dependent. Small particles (155 nm and 200 nm) exhibiting a maximal association with increasing invasin concentration whilst the larger particles (375 nm and 600 nm) provide a minimum at low invasin concentrations. Modified particle cell association provided results commensurate with a receptor dependent uptake mechanism related to the presence of invasin. The size and surface concentration dependency however illustrate that application of these ligands to particulate drug delivery or targeting systems will be controlled by their natural cellular association properties.
ISSN:	0724-8741 1573-904X