Solid Peptide Nanoparticles : Structural Characterization and Quantification of Cargo Encapsulation

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 diams. 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. CD 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 ppts. amorphously. The unacetylated deriv. of LCD3ac (LCD3) displays ?-helical character in CD. During the process of bead formation, CD3ac can take up and enrich water-sol. and - insol. cargo compds., which is exemplified by the encapsulation of rose bengal (RB) and 5-carboxy-fluorescein (CF), two xanthene derivs. We confirmed their presence in CD3ac beads by confocal fluorescence microscopy and quantified the encapsulation efficiency by absorption measurements of dissolved RB-contg. peptide bead suspensions. Loaded CD3ac beads consist of up to 40 mol-% RB, which corresponds to a logarithmic partition coeff. of 2.95. To the best of our knowledge CD3ac is the first peptide synthesized by Fmoc chem. which forms solid particles in the nano- and micrometer size range and holds promise for drug delivery applications. [on SciFinder(R)]