Nanostructure-templated control of drug release from peptide amphiphile nanofiber gels

John B. Matson, Christina J. Newcomb, Ronit Bitton, Samuel I. Stupp

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


High aspect ratio peptide nanofibers have potential as biodegradable vehicles for drug delivery. We report here the synthesis of four self-assembling peptide amphiphiles (PAs) containing a lysine ε-amine-derivatized hydrazide that was systematically placed at different positions along the backbone of the peptide sequence C 16V 2A 2E 2 (where C 16 = palmitic acid). Hydrazones were formed from each hydrazide by condensation with the solvatochromic dye 6-propionyl-2- dimethylaminonaphthalene (Prodan), which is typically used to probe cell membranes. All four compounds were found to self-assemble into nanofibers, and Prodan release was measured from filamentous gels prepared by screening PA charges with divalent cations. Near zero-order release kinetics were observed for all nanofibers, but release half-lives differed depending on the position of the fluorophore in the PA sequence. Dye release kinetics were rationalized through the use of cryogenic transmission electron microscopy, small-angle X-ray scattering, fluorescence spectroscopy, fluorescence anisotropy, circular dichroism, and partition coefficient calculations. Relative release rates were found to correlate directly with fluorophore mobility, which varied inversely with packing density, degree of order in the hydrophobic PA core, and the β-sheet character of the peptide.

Original languageEnglish
Pages (from-to)3586-3595
Number of pages10
JournalSoft Matter
Issue number13
StatePublished - 7 Apr 2012
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • Condensed Matter Physics


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