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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.
This article was published in the following journal.
Name: ACS nano
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A layer of protein coating adsorbed by NANOPARTICLES upon entry into PLASMA or other protein-containing biological fluids, which affects how nanoparticles are internalized by cells and cleared from the body.
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
A retinoblastoma-binding protein that is involved in CHROMATIN REMODELING, histone deacetylation, and transcription repression. Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 where it plays a role in the deposition of NUCLEOSOMES on newly synthesized DNA.
A retinoblastoma-binding protein that is found as a subunit of protein complexes involved in the acetylation of newly synthesized histones. Although initially discovered as a retinoblastoma binding protein, it also has an affinity for core HISTONES and plays a role in recruiting core histone proteins to the active site of the acetyltransferase enzyme complexes.
A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.
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<!--LGfEGNT2Lhm-->Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. <!--LGfEGNT2Lhm-->Drug delivery technologies are <!--LGfEGNT2Lhm-->patent pr...