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% w/w each) and bath sonication, displayed nanometric size (209.4nm, PDI = 0.19), and cationic zeta potential (+28.0mV). 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 μg/cm2) and 4.5-fold (2.8±0.8 μg/cm2) increases in PTX penetration into the stratum corneum and viable skin layers, respectively, were observed after 12hours. 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 by 1.5- and 1.2-fold (1.55 and 35.10 μM for PTX and 5-FU, respectively) compared to the control solutions. IC50 values found for keratinocytes were higher (5.74 and 162.6 μM 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.