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

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.

PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma

“…This high heterodispersity of the 321 nm NPs may have resulted in the formation of a larger physical barrier to the passage of light through the sample during measurement, hence, giving a lower % PA for these NPs. The results observed in this study were similar to the platelet aggregometry data for thrombin-activated WPs incubated with various sized NPs which we reported previously [ 9 ]. The response of platelets in PRP in the presence of NPs did not appear to vary despite the additional components present in PRP.…”

“…Using the formulation parameters as those used in our previous study, PLGA-PEG NPs of three different sizes similar to those previously reported, were obtained [ 9 ]. The average particle size (PS) and polydispersity index (PDI) obtained were 113 ± 7.22, 321 ± 46.43, and 585 ± 5.87 nm and 0.10 ± 0.03, 0.55 ± 0.07, and 0.67 ± 0.03 respectively, for PLGA-PEG concentrations of 10, 55, and 100 mg/mL.…”

“…NPs of 321 nm showed a higher reduction in % PA of platelets in PRP. This was related to the greater tendency of the 321 nm NPs to aggregate as compared with the larger-sized NPs of 585 nm [ 9 ]. This high heterodispersity of the 321 nm NPs may have resulted in the formation of a larger physical barrier to the passage of light through the sample during measurement, hence, giving a lower % PA for these NPs.…”

“…The interaction of NPs with platelets may lead to disruption of normal platelet function, predominantly resulting in the inadvertent generation of a thrombus leading to a cardiovascular event, such as myocardial infarct or stroke [ 8 ]. We previously reported the dependency of size and concentration of PLGA-PEG NPs on the aggregation profile of washed platelets (WPs) and showed a delay in the aggregation profile of WPs in the presence of NPs of 348 and 576 nm at NP concentrations of 1.5–2.2 mg/mL [ 9 ].…”

PLGA Based Drug Carrier and Pharmaceutical Applications: The Most Recent Advances

“…PLGA toxicity was investigated by Bakhaidar et al [ 29 ]. Here, the researchers studied the impact of size-selected PLGA–PEG nanoparticles on platelet activation and aggregation.…”