One-step preparation of polyelectrolyte-coated PLGA microparticles and their functionalization with model ligands

• Published in: Journal of controlled release Vol. 111; no. 1; pp. 135 - 144
• Main Authors: Fischer, Stefan, Foerg, Christina, Ellenberger, Sabine, Merkle, Hans P., Gander, Bruno
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.03.2006; Elsevier
• Subjects: Biocompatible Materials - chemistry; Biodegradation, Environmental; Biological and medical sciences; Biotin - analogs & derivatives; Biotin - chemistry; Chemistry, Pharmaceutical - methods; Chitosan; Chitosan - chemistry; Electrolytes - chemistry; Fluorescamine - chemistry; General pharmacology; Lactic Acid - chemistry; Ligands; Medical sciences; Microparticles; Microscopy, Confocal; Microscopy, Electron, Scanning; Molecular Weight; Nanostructures - chemistry; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA; Polyethylene Glycols - chemistry; Polyglycolic Acid - chemistry; Polymers - chemistry; Spectrometry, X-Ray Emission; Static Electricity; Static micromixer; Surface modification; Technology, Pharmaceutical - methods; Surface modification; PLGA; Chitosan; Static micromixer; Microparticles; Pharmaceutical technology; Ligand; Glycolic acid polymer; Polyelectrolyte; Lactic acid polymer; Preparation; Microparticle; Copolymer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2005.11.015

This work aimed at the development of a novel surfactant-free, one-step process for the concomitant formation of poly(lactide- co-glycolide) (PLGA) microparticles (MP) and surface coating with the polyelectrolyte chitosan, which is suitable for subsequent covalent conjugation of bioactive ligands. The technology is based on solvent extraction from an O/W-dispersion using a static micromixer. Surface coating occurred through interaction of the negatively charged, nascent PLGA MP with the polycationic chitosan, which was dissolved in the aqueous extraction fluid. Particles of 1–10 μm in diameter were produced with excellent reproducibility. The chitosan-coated PLGA MP were spherical and showed a smooth surface without pores, as demonstrated by scanning electron microscopy (SEM). The chitosan coatings were characterized by zeta potential measurements and X-ray photoelectron spectroscopy (XPS). The functional amino groups of chitosan were used to conjugate two model ligands to the coating, i.e. fluorescamine and NHS-PEG-biotin. The presence of the conjugated ligands was revealed by confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS). Evidence for biotinylation was demonstrated through binding of fluorescently labelled streptavidin. The developed platform technology is straightforward and flexible. Future studies will focus on the design of microparticulate carriers with bioactive surfaces, e.g. as antigen delivery systems.