Ternary polysaccharide complexes: Colloidal drug delivery systems stabilized in physiological media

Chitosan-hyaluronan (HYA) polyelectrolyte complexes (PECs) were designed to maintain their colloidal stabilities in physiological ionic strength and pH, via a new concept of ternary complexes. This strategy relied on the formation of a binary PEC between chitosan and a strong polyacid, dextran sulphate (DS) or heparin (HEP), and further functionalization with HYA. The major parameter leading to stabilized colloids was a high ratio of the degrees of polymerization of chitosan versus the strong polyacid. The process afforded either positive or negative particles when HYA was used in default or in excess (vs. chitosan) for the functionalization of the binary complexes. The most stable formulations were loaded with an antiretroviral drug tenofovir (TF), and could be surface functionalized with targeting IgAs. In vitro, the cationic TF loaded ternary complexes exhibited an inhibition of infection of PBMCs by the HIV-1 virus, superior to the free drug.