Chitosan-modified hyaluronic acid-based nanosized drug carriers.

Fabrication possibilities, detailed size and structural characterization of biodegradable chitosan (Chit) polysaccharide-modified hyaluronic acid (HyA)-based colloidal carriers are demonstrated. The negatively charged and highly hydrophilic HyA polymer chains have been ionically modified by positively charged pure Chit and crosslinked Chit macromolecules at various Chit/HyA weight ratios, which resulted in the formation of carrier nanoparticles (NPs) having three different nanostructures depending on the polymer concentrations. Electrostatically-compensated Chit/HyA polymer coils with loose colloidal structure, tripolyphosphate (TPP)-crosslinked Chit-TPP/HyA NPs having interpenetrating polymer network and well-defined Chit-TPPcore-HyAshell NPs with diameters of 100-300 nm were also prepared and were loaded with tocopherol (TCP) and cholecalciferol (D3) having Vitamin E and D activity, respectively. By using rheological, particle charge titration and conductivity studies we first confirmed that the expected 1:1 Chit/HyA monomer molar ratio is strongly influenced by the pH of the polymer solutions as well as the deacetylation degree of Chit which are crucial factors for the solubility, purity and the quality of the commercially available biocompatible Chit in aqueous medium. Encapsulation studies revealed that D3 could be better incorporated in every system, especially in Chit-TPP/HyA NPs, while for TCP the simple Chit/HyA polymer coils were the most promising carriers.