Structural Determinants of the Stability of Enzyme-Responsive Polyion Complex Nanoparticles Targeting Pseudomonas aeruginosa’s Elastase

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
  • Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
  • University of Bradford
  • Current address: Department of Microbiology and Molecular Genetics; University of Texas Health Science Center; Houston (TX) USA
  • School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Abstract

Here, we report how the stability of polyion complex (PIC) particles containing Pseudomonas aeruginosa’s elastase (LasB) degradable peptides and antimicrobial poly(ethylene imine) is significantly improved by careful design of the peptide component. Three LasB‐degradable peptides are reported herein, all of them carrying the LasB‐degradable sequence −GLA− and for which the number of anionic amino acids and cysteine units per peptide were systematically varied. Our results suggest that while net charge and potential to cross‐link via disulfide bond formation do not have a predictable effect on the ability of LasB to degrade these peptides, a significant effect of these two parameters on particle preparation and stability is observed. A range of techniques has been used to characterize these new materials and demonstrates that increasing the charge and cross‐linking potential of the peptides results in PIC particles with better stability in physiological conditions and upon storage. These results highlight the importance of molecular design for the preparation of PIC particles and should underpin the future development of these materials for responsive drug delivery.

Details

Original languageEnglish
JournalChemNanoMat
Early online date23 Apr 2018
Publication statusE-pub ahead of print - 23 Apr 2018