Chitosan has the potential to act as mediators of DNA transfection targeted to phagocytic cells such as macrophages, and to protect against biological degradation by nucleases as well as enhance gene expression. However, the poor solubility of Chitosan is the major limiting factor in its utilization. 2-hydroxypropyltrimcthyl ammonium chloride Chitosan has be prepared successfully through covalent binding of 2,3-Epoxypropyltrimethylammonium chloride ligands to the polymer’s primary amino groups and the polymer’s structure was verified with FT-IR spectra and NMR spectra. The new polymers were obtained with degree of quaternization (DQ) values around 34%, except in the case of the Phe-derived polymer, and thus possess reduced net positive charge as compared to the parent Chitosan. This study provided the new peptide-Chitosans with full water-solubility over practically the entire physiological pH range and led to more disordered. Globally, the new peptide Chitosans and especially the Asp-derived polymer, possess physico-chemical properties that turn them into promising candidates as novel Chitosan-based vaccine delivery systems.