Evaluation of polyelectrolyte nanoparticles of chitosan and hyaluronic acid as topical delivery systems for cytotoxic agents

In this study, we developed polyelectrolyte complexes (PECs), composed of hyaluronic acid and chitosan, aiming at obtaining a bioadhesive topical formulation for potential application for skin cancer treatment. Selected nanocarriers were obtained at a 1:1 (w/w) ratio of polyelectrolytes (0.25 mg/mL each) and probe sonication, displayed nanometric size (209.4 nm, PDI = 0.19), and cationic zeta potential (+28.0 +28.0 mV). PECs presented bioadhesive potential, demonstrated by shifts in size and zeta potential upon incubation with mucin, and reduced transepidermal water loss. Paclitaxel (PTX) and 5-fluorouracil (5-FU), cytotoxic drugs with distinct physical- chemical characteristics, were incorporated at 0.25 and 0.75 %, respectively; propylene glycol addition was necessary for PTX incorporation. Compared to the control, 2.3- (9.4 +/- 3.6 +/- 3.6 mu g/cm2) 2 ) and 4.5-fold (2.8 +/- 0.8 +/- 0.8 mu g/cm2) 2 ) increases in PTX penetration into the stratum corneum and viable skin layers, respectively, were observed after 12 hours. No increase in 5-FU penetration was demonstrated. Incorporation in PECs resulted in slight increases in the cytotoxicity of PTX and 5-FU against melanoma cells, reducing IC50 50 values by 1.5- and 1.2-fold (1.55 and 35.10 mu M for PTX and 5-FU, respectively) compared to the control solutions. IC50 50 values found for keratinocytes were higher (5.74 and 162.6 mu M for paclitaxel and 5-FU, respectively). At non-cytotoxic concentrations, drug loaded PECs promoted 24-31 % reductions on cell migration, suggesting that drug incorporation in PECs did not hinder their biological effects.