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In this study, two types of cutaneous-directed nanoparticles are proposed for the co-encapsulation of imiquimod (a drug approved for the treatment of basal cell carcinoma) and copaiba oil (oil that exhibits anti-proliferative properties). Nanostructured copaiba capsules (NCC_Imq) were prepared using the interfacial deposition method, and nanostructured Brazilian lipids (NBL_Imq) were prepared by high-pressure homogenization. The formulations exhibited average diameter, zeta potential, pH and drug content of approximately 200 nm, − 12 mV, 6 and 1 mg mL^− 1, respectively. In addition, the formulations exhibited homogeneity regarding particle size, high encapsulation efficiency and stability. Both nanocarriers controlled imiquimod release, and NBL_Imq exhibited slower drug release (p < 0.05), likely due to increased interaction of the drug with the solid lipid (cupuaçu seed butter). The in vitro evaluation of the …