Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Tobias AA Bauer
  • Irina Alberg
  • Lydia AA Zengerling
  • Pol Besenius
  • Kaloian Koynov
  • Bram Slutter
  • Rudolf Zentel
  • Ivo Que
  • Heyang Zhang
  • Matthias Barz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001031629700001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1021/acs.biomac.3c00308
eISSN
1526-4602
Externe Identifier
  • Clarivate Analytics Document Solution ID: O8BR5
  • PubMed Identifier: 37449781
ISSN
1525-7797
Ausgabe der Veröffentlichung
8
Zeitschrift
BIOMACROMOLECULES
Paginierung
3545 - 3556
Datum der Veröffentlichung
2023
Status
Published
Titel
Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice
Sub types
  • Article
Ausgabe der Zeitschrift
24

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Tobias A Bauer
  • Irina Alberg
  • Lydia A Zengerling
  • Pol Besenius
  • Kaloian Koynov
  • Bram Slütter
  • Rudolf Zentel
  • Ivo Que
  • Heyang Zhang
  • Matthias Barz
DOI
10.1021/acs.biomac.3c00308
eISSN
1526-4602
ISSN
1525-7797
Ausgabe der Veröffentlichung
8
Zeitschrift
Biomacromolecules
Sprache
en
Online publication date
2023
Paginierung
3545 - 3556
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
American Chemical Society (ACS)
Herausgeber URL
http://dx.doi.org/10.1021/acs.biomac.3c00308
Datum der Datenerfassung
2023
Titel
Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice
Ausgabe der Zeitschrift
24

Datenquelle: Crossref

Abstract
Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-<i>block</i>-poly(<i>S</i>-ethylsulfonyl-l-cysteine) [pSar-<i>b</i>-pCys(SO<sub>2</sub>Et)] were employed. While the pCys(SO<sub>2</sub>Et) chain lengths varied from <i>X</i><sub><i>n</i></sub> = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO<sub>2</sub>Et)]<sub>17</sub>, increasing the cross-linking density or the pCys(SO<sub>2</sub>Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.
Addresses
  • Leiden Academic Centre for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Autoren
  • Tobias A Bauer
  • Irina Alberg
  • Lydia A Zengerling
  • Pol Besenius
  • Kaloian Koynov
  • Bram Slütter
  • Rudolf Zentel
  • Ivo Que
  • Heyang Zhang
  • Matthias Barz
DOI
10.1021/acs.biomac.3c00308
eISSN
1526-4602
Externe Identifier
  • PubMed Identifier: 37449781
  • PubMed Central ID: PMC10428167
Funding acknowledgements
  • Max-Planck-Gesellschaft:
  • Evonik Stiftung:
  • Stichting Voortgezet Onderwijs van de Bovenwindse Eilanden:
  • Deutsche Forschungsgemeinschaft: SFB1066-3 - B8
Open access
true
ISSN
1525-7797
Ausgabe der Veröffentlichung
8
Zeitschrift
Biomacromolecules
Schlüsselwörter
  • Plasma
  • Animals
  • Humans
  • Mice
  • Polymers
  • Tissue Distribution
  • Micelles
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Open access status
Open Access
Paginierung
3545 - 3556
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
24

Files

https://pubs.acs.org/doi/pdf/10.1021/acs.biomac.3c00308 https://europepmc.org/articles/PMC10428167?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) [pSar-b-pCys(SO2Et)] were employed. While the pCys(SO2Et) chain lengths varied from Xn = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO2Et)]17, increasing the cross-linking density or the pCys(SO2Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.
Autoren
  • Tobias A Bauer
  • Irina Alberg
  • Lydia A Zengerling
  • Pol Besenius
  • Kaloian Koynov
  • Bram Slütter
  • Rudolf Zentel
  • Ivo Que
  • Heyang Zhang
  • Matthias Barz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37449781
DOI
10.1021/acs.biomac.3c00308
eISSN
1526-4602
Externe Identifier
  • PubMed Central ID: PMC10428167
Ausgabe der Veröffentlichung
8
Zeitschrift
Biomacromolecules
Schlüsselwörter
  • Humans
  • Animals
  • Mice
  • Micelles
  • Tissue Distribution
  • Polymers
  • Plasma
Sprache
eng
Country
United States
Paginierung
3545 - 3556
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
24

Datenquelle: PubMed

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