Bioreducible insulin-loaded nanoparticles and their interaction with model lipid membranes
Journal article, 2011

To improve design processes in the field of nanomedicine, in vitro characterization of nanoparticles with systematically varied properties is of great importance. In this study, surface sensitive analytical techniques were used to evaluate the responsiveness of nano-sized drug-loaded polyelectrolyte complexes when adsorbed to model lipid membranes. Two bioreducible poly(amidoamine)s (PAAs) containing multiple disulfide linkages in the polymer backbone (SS-PAAs) were synthesized and used to form three types of nanocomplexes by self-assembly with human insulin, used as a negatively charged model protein at neutral pH. The resulting nanoparticles collapsed on top of negatively charged model membranes upon adsorption, without disrupting the membrane integrity. These structural rearrangements may occur at a cell surface which would prevent uptake of intact nanoparticles. By the addition of glutathione, the disulfide linkages in the polymer backbone of the SS-PAAs were reduced, resulting in fragmentation of the polymer and dissociation of the adsorbed nanoparticles from the membrane. A decrease in ambient pH also resulted in destabilization of the nanoparticles and desorption from the membrane. These mimics of intracellular environments suggest dissociation of the drug formulation, a process that releases the protein drug load, when the nanocomplexes reaches the interior of a cell. (C) 2011 Elsevier Inc. All rights reserved.

1993

in-vitro

side-chains

Supported

lmadge je

p247

carriers

poly(amido amine)s

protein therapeutics

polymers

v10

Protein delivery

biomedical applications

lipid bilayer

gene delivery

Nanoparticle

QCM-D

anticancer therapeutics

cells

Poly(amidoamine)s

Author

Rickard Frost

Chalmers, Applied Physics, Biological Physics

G. Coue

University of Twente

J. F. J. Engbersen

University of Twente

Michael Zäch

Chalmers, Applied Physics, Chemical Physics

Bengt Herbert Kasemo

Chalmers, Applied Physics, Chemical Physics

Sofia Svedhem

Chalmers, Applied Physics, Biological Physics

Journal of Colloid and Interface Science

0021-9797 (ISSN) 1095-7103 (eISSN)

Vol. 362 2 575-583

Areas of Advance

Nanoscience and Nanotechnology

Life Science Engineering (2010-2018)

Materials Science

Subject Categories

Chemical Sciences

DOI

10.1016/j.jcis.2011.05.082

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6/8/2018 5