| Summary: |
Nanoparticulate drug carriers such as nanocapsules and drug polymer conjugates can be used to improve the therapeutic index of drugs by modifying their distribution, and thus increasing their efficacy and/or reducing their toxicity. If these systems are carefully designed with respect to the target and the route of administration, they may provide one solution to some of the delivery problems posed by new classes of active molecules, such as peptides and proteins. Peptides are potential therapeutic drugs for the treatment of a variety of diseases including cancer and neurodegenerative disorders. However their wider use has been hindered by issues such as poor bioavailability in vivo. The applications considered in this project are concentrated in design controlled delivery systems of peptides that were proved to be valuable potential candidates for amyloid-related diseases in particular Alzheimer's disease. Therefore, based in multidisciplinary fundamental research, the goals of this project are to produce nanocapsules with specific properties and to prepare polymer conjugates so that the bioavailability of an active peptide will increase. The peptide to be encapsulated and conjugated is a short sequence homologous to the central region of amyloid beta-peptide (residues 17-21) that contains proline residues. Amyloid beta-peptide is the major fibrillar component of neuritic plaques in Alzheimer's disease and its aggregation is inhibited by the short peptide. By encapsulating or conjugating the active peptide it is expected to increase its plasma residence time and therapeutic index and to reduce its immunogenicity. |