Investigation of the interaction of biodegradable micro- and nanoparticulate drug delivery systems with platelets

Abstract

Objectives Biodegradable micro- and nanoparticles are being increasingly investigated for drug delivery and targeting of therapeutics. The size and surface properties of these particles are important factors influencing their interaction and uptake by various cells, tissues and organs. Optimising these properties, to enhance cellular uptake, may increase their potential for interaction with other physiological components such as platelets resulting in platelet activation and inappropriate thrombus formation. The aim of this study was to investigate the potential interaction of particulates with platelets. Methods Biodegradable micro- and nanoparticles based on poly-lactide-co-glycolide (PLGA), poly-lactide-co-glycolide–macrogol (PLGA-macrogol) and chitosan were prepared using solvent evaporation, spray drying or solvent dispersion techniques. Key findings Microparticles formulated had a median diameter (D50%) of 2–9 µm, while nanoparticles had an average diameter of 100–500 nm. The surface morphology ranged from smooth and spherical to irregular depending on polymer and preparation method used. Particles, reconstituted in the concentration range of 0.1–500 µg/ml, were tested for their ability to induce or inhibit platelet aggregation. No effects on either induction of platelet activity or inhibition of aggregation were detected. Conclusions None of the particles examined were found to alter platelet activity. These results suggested that the biodegradable micro- and nanoparticles tested were safe for use as potential drug carriers of therapeutic agents.