Preparation of Poly(ethylene glycol) Protected Nanoparticles with Variable Bioconjugate Ligand Density

• Published in: Biomacromolecules Vol. 9; no. 10; pp. 2705 - 2711
• Main Authors: Gindy, Marian E, Ji, Shengxiang, Hoye, Thomas R, Panagiotopoulos, Athanassios Z, Prud’homme, Robert K
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.10.2008
• Subjects: Animals; Applied sciences; Biological and medical sciences; Cattle; Exact sciences and technology; Forms of application and semi-finished materials; General pharmacology; Ligands; Light; Maleimides - chemistry; Medical sciences; Miscellaneous; Molecular Conformation; Nanoparticles - chemistry; Nanotechnology - methods; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Polymer industry, paints, wood; Polymers - chemistry; Scattering, Radiation; Serum Albumin, Bovine - chemistry; Sulfhydryl Compounds - chemistry; Surface Properties; Technology of polymers; Surface reaction; End group; Chemical precipitation; Nanoparticle; Control release polymer; Drug carrier; Serum albumin; Ethylene oxide copolymer; Experimental study; Protein; Chemical coupling; Particle size distribution; Chemical modification; Caprolactone copolymer; Diblock copolymer; Manufacturing; Chemical reactivity; Aliphatic copolymer; Amphiphilic polymer
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/bm8002013

Maleimide-functional poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles (NPs) were prepared via the Flash NanoPrecipitation technique. Subsequent reaction with a model ligand, bovine serum albumin (BSA), was conducted using thiol-maleimide conjugation. Reaction of up to 22% of NP surface maleimide-PEG tethers was obtained, with the percent conversion being essentially independent of the ratio of maleimide-PEG to methyl-PEG over the range 30−100%, respectively. At the highest surface coverage, BSA is calculated to essentially cover the NP surface area. Reaction parameters (reaction order and docking constant) describing the extent of ligand conjugation were determined. The reaction order is applicable to the conjugation of ligands presenting free thiol functionalities, while the value of the docking constant is ligand-dependent and accounts for physical and dynamic properties of the ligand−PEG interaction. Jointly, the particle formation process, using block copolymer-directed kinetically controlled assembly and surface functionalization represent a versatile new platform for the preparation of bioconjugated NPs with accurate control of ligand density and minimal processing steps.