Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management

Zhang, Xiaopei; Xu, Duo; Jin, Xin; Liu, Gan; Liang, Sheng; Wang, Hui; Chen, Wei; Zhu, Xinyuan; Lu, Yunfeng

doi:10.1016/j.jconrel.2017.03.019

Cited by 26 publications

(22 citation statements)

References 31 publications

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“…To investigate whether the linear correlation between PK parameters with the K A value can be extended to other hydrophilic surfaces, we chose polyphosphoester (PEEP) and polyvinylpyrrolidone (PVP) as the hydrophilic moiety because PEEP and PVP can reduce macrophage clearance similar to PEG. ,, We synthesized a series of PEEP- b -PLA and PVP- b -PLA diblock polymers according to previous literature. ,,− The hydrophilic block (PEEP and PVP) with an identical molecular weight of 5 kDa and 5.7 kDa was chosen (the same with PEG), and the molecular weight of the PLA block ranged from 4540 to 14,400 Da and 4950 to 21,370 Da, respectively (Tables S3 and S4). PEEP- b -PLA and PVP- b -PLA NPs were formulated using the same method as PEG- b -PLA NPs, named as NP-9 to NP-15 and NP-16 to NP-22, of which the detailed preparation conditions are summarized in Tables S3 and S4.…”

Section: Results and Discussionmentioning

confidence: 99%

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

et al. 2020

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Polymeric nanoparticles (NPs) are an important category of drug delivery systems, and their in vivo fate is closely associated with delivery efficacy. Analysis of the protein corona on the 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 (K A), 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 (C max), 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 K A. Subsequently, we verified the reliability of the approach for in vivo fate prediction using poly(methoxyethyl ethylene phosphate)-block-poly(d,l-lactide) (PEEP-b-PLA) and poly(vinylpyrrolidone)-block-poly(d,l-lactide) (PVP-b-PLA) NPs, and the linear relationship between the K A value and their PK parameters further suggests that the protein binding affinity of polymeric NPs can be a direct indicator of their pharmacokinetics.

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Section: Results and Discussionmentioning

confidence: 99%

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

et al. 2020

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“…[77] Then, acryloylated enzymes, monomers, and crosslinkers are incubated in buffer solutions, and free radical polymerization can be initiated in those mild reaction conditions upon the addition of radical initiators. [77a] After purification by exclusion chromatography [78] or ion exchange chromatography, [79] stable polymeric nanocapsules are yielded. This two-step protocol is a widely used procedure for the preparation of enzyme-loaded nanocapsules.…”

Section: Cross-linked In Situ Polymerizationmentioning

confidence: 99%

Weaving Enzymes with Polymeric Shells for Biomedical Applications

Blum

et al. 2021

Advanced Materials

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the most common administration method. However, the sizes of most enzymes are smaller than the kidney filtration threshold (50-60 kDa), resulting in fast renal clearance and short half-lives. [5] Also, limited by its hydrophilicity and large molecular weight, it is difficult for exogenous enzyme macromolecules to pass through the cell membrane to effectively catalyze intracellular target reactions. [6] To date, most of the clinical protein therapeutics were explored toward extracellular targets owing to the low translocation efficiency. [7] However, for enzyme therapeutics, especially for the enzyme replacement therapy, intracellular delivery is considered critical for effective therapy. [8] Typically, even if a number of enzymes are transfected into

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“…43). [275][276][277][278] A prolonged plasma circulation time can be observed (as high as 7 days) with low level of immunogenicity. This in situ polymerization technique can be universally applied to a library of proteins, with different sizes, surface charges, and structures.…”

Section: In Situ Polymerization For Protein Modificationmentioning

confidence: 99%