Novel highly-soluble peptide-chitosan polymers: Chemical synthesis and spectral characterization

Novel water-soluble polymers, N-(gamma-propanoyl-valin)-chitosan and N-(gamma-propanoyi-aspartic acid)-chitosan, were synthesized by reaction of low molecular weight chitosan with N-alpha-(3-bromopropanoyl)-valine and N-alpha-(3-bromopropanoyl)-aspartic acid, respectively, under mild conditions. Prior to reaction with chitosan, the peptide substituents have been prepared by standard peptide chemistry methods from 3-bromopropanoic acid and the relevant a-amino acid tert-butyl esters. The chemical structure and physical properties of the novel chitosan derivatives were characterized by H-1 NMR and IR spectroscopy. The polymers are highly soluble in a wide pH range, which opens new perspectives for the applications of chitosan-based materials

Radiochemical and biological evaluation of novel Sm-153/Ho-166-amino acid-chitosan complexes

Sm-153/Ho-166-chitosan complexes have been considered promising agents for internal radiation therapy. By direct administration, complexes solution converts into a gel, at physiological pH, allowing its retention for a long time. Herein, we report on the synthesis of Sm-153/Ho-166 complexes with the novel amino acid-chitosan polymers, N-(gamma-propanoylvalin)-chitosan (CHICO-val) and N-(gamma-propanoyl-aspartic acid)-chitosan (CHICO-asp). The main goal of this study was to obtain data on the radiochemical and biological behaviour of these complexes and information regarding their therapeutic potential when compared to Sm-153/Ho-166-chitosan. Radiolabelling yield of Sm-153/Ho-166-amino acid-chitosan complexes was dependent on polymer concentration but less dependent on pH. Radiochemical stability was shown to be higher for amino acid-chitosans than for chitosan, with Sm-153/Ho-166-CHICO-val being stable up to 3 h, while Sm-153/Ho-166-CHICO-asp is stable up to 24 h. In the presence of ascorbic acid radiochemical stability of Sm-153/Ho-166-CHICO-val and Sm-153/Ho-166-CHICO was improved, decreasing for Sm-153/Ho-166-CHICO-asp. In vivo behaviour of Sm-153 complexes was studied in mice. The radioactive amino acid-chitosans can be directly injected into blood stream without significant retention on injection site, being trapped by liver. Biodistribution studies suggest that the radioactive amino acid-chitosans, due to its water solubility and stability may be considered potential candidates to be further explored for liver targeted nuclear therapy