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Effect of charge density on the interaction between cationic peptides and oppositely charged microgels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2010 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 21, 7207-7215 p.Article in journal (Refereed) Published
Abstract [en]

The effect of charge density on the interaction between cationic peptides and oppositely charged poly(acrylic acid-co-acrylamide) microgels was investigated together with effects of charge localization and interplay between electrostatic and hydrophobic interactions. The microgel charge content was controlled by varying acrylic acid/acrylamide ratios (25/75-100/0 mol %) in the microgel synthesis, whereas peptide charge density was controlled by using monodisperse peptides containing alanine and lysine in a series of repeated patterns (25-50 mol % lysine). Results show that peptide uptake in the microgels is largely determined by microgel charge density, whereas peptide-induced microgel deswelling kinetics is influenced by peptide charge density to a higher degree. Furthermore, electrolyte-induced peptide detachment is highly influenced by both microgel and peptide charge density. Thus, at high charge contrast, peptides could not be detached from the microgels, whereas reducing the charge density of either peptide or microgel promoted electrolyte-induced peptide release. The localization of charges in the peptide sequence also plays a significant role as the interaction strength increased for peptides where all charged groups are located at the end of the sequence, as opposed to homogenously distributed throughout the peptide. Such an asymmetrically charged peptide thus displayed higher uptake, faster deswelling response, and lower release degrees than its homogeneously charged analogue in microgels with high charge content, while these differences were absent for lower microgel charge densities. Hydrophobic substitutions (alanine → leucine) in the peptide chain at fixed charge content increased peptide binding strength and eliminated peptide detachment at high ionic strength. Theoretical modeling of the effect of peptide and microgel charge density on peptide-induced microgel deswelling gave good agreement with experimental results.

Place, publisher, year, edition, pages
2010. Vol. 114, no 21, 7207-7215 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-109208DOI: 10.1021/jp1016664ISI: 000278004300009PubMedID: 20459071OAI: oai:DiVA.org:uu-109208DiVA: diva2:271535
Available from: 2009-10-12 Created: 2009-10-12 Last updated: 2010-12-13Bibliographically approved
In thesis
1. Interaction Between Microgels and Oppositely Charged Peptides
Open this publication in new window or tab >>Interaction Between Microgels and Oppositely Charged Peptides
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lightly cross-linked polyelectrolyte microgels are materials with interesting properties for a range of applications. For instance, the volume of these particles can be drastically changed in response to pH, ionic strength, temperature, or the concentration of specific ions and metabolites. In addition, microgel particles can bind substantial amounts of oppositely charged substances, such as proteins and peptides, and release them upon changes in the external environment. Consequently, microgels have potential in catalysis, photonics, biomaterials, and not at least, as protective and stimuli-sensitive carriers for protein and peptide drugs.

In this thesis, the interaction between anionic microgels and cationic peptides was investigated by monitoring microgel deswelling and reswelling in response to peptide binding and release using micromanipulator-assisted light microscopy. In addition, peptide distribution in microgels was analyzed with confocal laser scanning microscopy and peptide uptake determined with solution depletion measurements. The aim of the thesis was to clarify how parameters such as peptide size, charge density, pH, ionic strength and hydrophobicity influences the peptide binding to, distribution in and release from, polyelectrolyte microgels.

Results obtained in this thesis show that electrostatic attraction is a prerequisite for interaction to occur although non-electrostatic contributions are responsible the finer details of the interactions. The size and charge density of the interacting peptides play a major role, as large and highly charged peptides are restricted to enter and interact with the microgel core, thus displaying a surface-confined distribution. The peptide-microgel interaction strength is highly reflected in the probability of peptides to be detached from the gel network. For instance, reducing the electrostatic interactions by adding salt induces significant peptide release of sufficiently small and moderately charged peptides, whereas longer and more highly charged peptides is retained in the microgel network due to the strong interaction, insufficient salt screening, and gel network pore size restriction. Decreasing the charge density of microgel network and/or peptides increases the probability for peptide detachment tremendously.

To summarize, interactions occurring in oppositely charged microgel-peptide systems can be tuned by varying parameters such as charge density and peptide size and through this, the peptide uptake, distribution and release can be controlled to alter the performance of microgels in peptide drug delivery.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 113
Keyword
antimicrobial peptides, binding, cationic peptides, confocal microscopy, deswelling, distribution, electrostatic, homopolypeptides, microgels, peptides, release, swelling
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-109203 (URN)978-91-554-7635-9 (ISBN)
Public defence
2009-11-27, B21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-11-06 Created: 2009-10-12 Last updated: 2009-11-06

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