title: Nanostructure-templated control of drug release from peptide amphiphile nanofiber gels.
abstract: 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(16)V(2)A(2)E(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.
authors.affiliation: Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL, 60611, USA. ; Tel: (+312) 503-6713.
authors.forename: John B
authors.initials: JB
authors.lastname: Matson
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Newcomb
authors.forename: Ronit
authors.initials: R
authors.lastname: Bitton
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp