title: Solid peptide nanoparticles--structural characterization and quantification of cargo encapsulation.
abstract: CD3ac, an uncharged and strongly hydrophobic 10 amino acid peptide (Ac-LK(Ac)-LK(Ac)-LK(Ac)-LW-DL-LW-DL-LW-DL-LW-NH2) was synthesized and purified. The peptide readily dissolves in ethanol and--upon solvent exchange to water--assembles into solid spherical particles with diameters of around 500 nm and low size-polydispersity. CD3ac self-assembles in a convenient one-step-process in the absence of a templating two-phase solvent system or any other templating agents. Circular dichroism reveals a gramicidin-like secondary structure, which can be attributed to the presence of D-leucine, whereas LCD3ac, a peptide of identical constitution yet composed entirely of L-amino acids precipitates amorphously. The unacetylated derivative of LCD3ac (LCD3) displays α-helical character in circular dichroism. During the process of bead formation, CD3ac can take up and enrich water-soluble and--insoluble cargo compounds, which is exemplified by the encapsulation of rose bengal (RB) and 5-carboxy-fluorescein (CF), two xanthene derivatives. We confirmed their presence in CD3ac beads by confocal fluorescence microscopy and quantified the encapsulation efficiency by absorption measurements of dissolved RB-containing peptide bead suspensions. Loaded CD3ac beads consist of up to 40 mol-% RB, which corresponds to a logarithmic partition coefficient of 2.95. To the best of our knowledge CD3ac is the first peptide synthesized by Fmoc chemistry which forms solid particles in the nano- and micrometer size range and holds promise for drug delivery applications.
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland. christian_dittrich@hms.harvard.edu
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meier
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D016503:Drug Delivery Systems / Q000379:methods*; D000431:Ethanol; D005452:Fluoresceins; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics; D012395:Rose Bengal; D014867:Water
chemical_list: D005452:Fluoresceins; D010455:Peptides; D014867:Water; D012395:Rose Bengal; D000431:Ethanol; C045132:4-carboxyfluorescein