Self-assembly of recombinant amphiphilic oligopeptides into vesicles.
The aim of the present study was to design amphiphilic oligopeptides that can self-assemble into vesicular structures. The ratio of hydrophilic to hydrophobic block length was varied, and peptides were designed to have a hydrophobic tail in which the bulkiness of the amino acid side groups increases toward the hydrophilic domain (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu(2/7)-COOH). These peptides were recombinantly produced in bacteria as an alternative to solid-phase synthesis. We demonstrate with different complementary techniques (dynamic and static light scattering, tryptophan fluorescence anisotropy, and electron microscopy) that these amphiphilic peptides spontaneously form vesicles with a radius of approximately 60 nm and a low polydispersity when dispersed in aqueous solution at neutral pH. Morphology and size of the vesicles were relatively insensitive to the variations in hydrophilic block length. Exposure to acidic pH resulted in formation of visible aggregates, which could be fully reversed to vesicles upon pH neutralization. In addition, it was demonstrated that water-soluble molecules can be entrapped inside these peptide vesicles. Such peptide vesicles may find applications as biodegradable drug delivery systems with a pH-dependent release profile.
van Hell
Albert J
AJ
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Costa
Cristina I C A
CI
Flesch
Frits M
FM
Sutter
Marc
M
Jiskoot
Wim
W
Crommelin
Daan J A
DJ
Hennink
Wim E
WE
Mastrobattista
Enrico
E
D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D005454:Fluorescence Polarization; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D006863:Hydrogen-Ion Concentration; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000737:chemistry*
D005452:Fluoresceins; D009842:Oligopeptides; D013501:Surface-Active Agents; C007740:fluorexon