Development of chitosan-hyaluronic acid polyelectrolyte nanoparticles for intraductal delivery

Abstract

Polyelectrolytes are polymeric macromolecules with positive or negative charges. Through electrostatic interaction, oppositely charged polyelectrolytes can form complexes spontaneously, which presents many applications and utilities. Considering the simple, efficient and low-cost process to obtain these molecules, as well as its good biodegradability, biocompatibility and low toxicity, polyelectrolyte complexes (PECs) can be used as nanocarriers for drug incorporation, seeking the optimization of bioavailability, modulation of release and residence time in the target site. A promising application is within the treatment of breast cancer, a disease with high incidence and prevalence worldwide that lacks less invasive therapeutic alternatives. Therefore, it is proposed the development of polyelectrolyte nanoparticles composed of hyaluronic acid and chitosan, which will be latter incorporated into Poloxamer 407 dispersions, aiming to obtain a formulation for intraductal administration and a jellified pharmaceutical form for topical application. The developed nanocarriers will be used to encapsulate paclitaxel, piplartine and 5-fluorouracil, looking for the evaluation of the system's capacity of incorporation of molecules with different solubilities. In the formation process of PECs, different conditions will be employed to analyze its influence in the system's properties, which will be characterized through size particle determination, polydispersity index and zeta potential. Lastly, after selecting the optimized formulation, mammary tissue localization and cutaneous penetration assays will be conducted. (AU)