Self-assembled hydrophobic Ala-Aib peptide encapsulating curcumin: a convenient system for water insoluble drugs

The exploitation of self-assembled systems to improve the solubility of drugs is getting more and moreattention. Among the different types of self-assembled biomaterials, peptides and in particular peptidescontaining non-coded amino acids (NCAPs) are promising because their use opens the door to morestable materials inducing increased stability to proteolysis. New classes of NCAP, Ac-Ala-X-Ala-Aib-AlaCONH2 (X ¼ alpha-aminoisobutyric acid (Aib) or X ¼ cyclopentane amino acid (Ac5c)) have beenprepared and the correlation between the different secondary peptide structure and solvent (i.e. CD3CN,CD3OH, H2O/D2O) verified by NMR. Furthermore, the formation of a nanocolloidal system in water wasdeeply studied by DLS and the morphology of the obtained spherical aggregates with nanometricdimensions was assessed by TEM. Aib containing pentapeptide was selected for greater ease ofsynthesis. Its ability to encapsulate curcumin, as a model insoluble drug molecule, was investigated usingfluorescence emission and confocal microscopy analyses. Two different approaches were used to studythe interaction between curcumin and peptide aggregates. In the first approach peptide aggregates wereformed in the presence of curcumin, while in the second approach curcumin was added to the alreadyformed peptide aggregates. We succeeded in our challenge by using the second approach and 53.8% ofadded curcumin had been encapsulated.