Evidence map›Paper›PMID 34314146›Full record

ArticleBiomacromolecules2021

Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation

Caitlin L Maikawa, Andrea I d'Aquino, Eric T Vuong, Bo Su, Lei Zou, Peyton C Chen, Leslee T Nguyen, Anton A A Autzen, Joseph L Mann, Matthew J Webber and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomacromolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Caitlin L MaikawaDepartment of Bioengineering, Stanford University, Stanford, California 94305, United States.
Andrea I d'AquinoDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Eric T VuongDepartment of Bioengineering, Stanford University, Stanford, California 94305, United States.
Bo SuDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Lei ZouDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Peyton C ChenDepartment of Bioengineering, Stanford University, Stanford, California 94305, United States.
Leslee T NguyenDepartment of Biochemistry, Stanford University, Stanford, California 94305, United States.
Anton A A AutzenDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Joseph L MannDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Matthew J WebberDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.ORCID 0000-0003-3111-6228
Eric A AppelDepartment of Bioengineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0002-2301-7126

Funding

Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Co-Formulations of Amylin Analogues with Insulin Analogues for Treatment of DiabetesR01DK119254 · NIDDK · STANFORD UNIVERSITY · PI APPEL, ERIC ANDREW · 2019 to 2023
$2.9M
NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK119254
6 · The paper itself

Abstract

Proteins are an impactful class of therapeutics but can exhibit suboptimal therapeutic performance, arising from poor control over the timescale of clearance. Covalent PEGylation is one established strategy to extend circulation time but often at the cost of reduced activity and increased immunogenicity. Supramolecular PEGylation may afford similar benefits without necessitating that the protein be permanently modified with a polymer. Here, we show that insulin pharmacokinetics can be modulated by tuning the affinity-directed dynamics of a host-guest motif used to non-covalently endow insulin with a poly(ethylene glycol) (PEG) chain. When administered subcutaneously, supramolecular PEGylation with higher binding affinities extends the time of total insulin exposure systemically. Pharmacokinetic modeling reveals that the extension in the duration of exposure arises specifically from decreased absorption from the subcutaneous depot governed directly by the affinity and dynamics of host-guest exchange. The lifetime of the supramolecular interaction thus dictates the rate of absorption, with negligible impact attributed to association of the PEG upon rapid dilution of the supramolecular complex in circulation. This modular approach to supramolecular PEGylation offers a powerful tool to tune protein pharmacokinetics in response to the needs of different disease applications.

Indexed as

Polyethylene GlycolsPolymersInsulinProteinsInsulinPolyethylene GlycolsPolymersProteins

Identifiers

PMID34314146
PMCPMC8627827

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.