Effect of Size and Concentration of PLGA-PEG Nanoparticles on Activation and Aggregation of Washed Human Platelets

Pharmaceutics. 2019 Oct 4;11(10):514. doi: 10.3390/pharmaceutics11100514.

Abstract

Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and blood constituents, presenting possible safety risks. While NPs investigated are predominantly based on the biodegradable, biocompatible, and FDA approved poly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been reported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined. The aims of this study were to determine the impact of size-selected PLGA-PEG (PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three average sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0-2.2 mg/mL on the activation and aggregation of washed human platelets (WP) was examined. The results of this study show, for the first time, NPs of all sizes associated with the surface of platelets, with >50% binding, leading to possible internalisation. The NP-platelet interaction, however, did not lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The outcome of this study is promising, suggesting that these NPs could be potential carriers for targeted drug delivery to platelets.

Keywords: PLGA-PEG; activation; aggregation; binding; nanoparticles; platelet; uptake.