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Protein Binding Affinity of Polymeric Nanoparticles as a Direct Indicator of Their Pharmacokinetics.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Protein Binding Affinity of Polymeric Nanoparticles as a Direct Indicator of Their Pharmacokinetics."

Polymeric nanoparticles (NPs) are important category of drug delivery systems, and their in vivo fate is closely associated with delivery efficacy. Analysis of the protein corona on surface of NPs to understand the in vivo fate of different NPs has been shown to be reliable but complicated and time-consuming. In this work, we establish a simple approach for predicting the in vivo fate of polymeric NPs. We prepared a series of poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-b-PLA) NPs with different protein binding behaviors by adjusting their PEG densities, which were determined by analyzing the serum protein adsorption. We further determined the protein binding affinity, denoted as the equilibrium association constant (KA), to correlate with in vivo fate of NPs. The in vivo fate, including blood clearance and Kupffer cell uptake, was studied, and the maximum concentration (Cmax), the area under the plasma concentration-time curve (AUC) and the mean residence time (MRT) were negatively linearly dependent, while Kupffer cell uptake was positively linearly dependent on KA. Subsequently, we verified the reliability of the approach for in vivo fate prediction using poly(methoxyethyl ethylene phosphate)-b-poly(D,L-lactide) (PEEP-b-PLA) and poly(vinylpyrrolidone)-b-poly(D,L-lactide) (PVP-b-PLA) NPs, and the linear relationship between the KA value and their PK parameters further suggest that the protein binding affinity of polymeric NPs can be a direct indicator of their pharmacokinetics.

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This article was published in the following journal.

Name: ACS nano
ISSN: 1936-086X
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