Abstract The high incidence of melanoma has received significant attention. Despite advances in early detection and standard treatment options, new strategies that improve therapy with reduced side effects are highly desirable. Several studies have demonstrated the efficiency of doxorubicin (Dox) to treat melanoma, however, side effects limit its clinical use. Drug delivery systems, especially nanostructured ones, are a useful approach to enhance antitumor activity and reduce toxicity of drugs. Here, the use of calcium phosphate nanoparticles functionalized with Dox and hyaluronic acid (N-Dox) to enhance Dox antiproliferative activity is reported. The effects were accessed in A-375 melanoma cells, in which N-Dox IC50 significantly decreased over 48 hours (0.14 ± 0.07 (M) compared to free drug (0.44 ± 0.25 (M) and showed selective action against A-375 when compared with HEK-293 cells. Treatment triggered DNA damage, increased nuclear area, and elicited senescent phenotype. Furthermore, it did not form colonies after 14 days of incubation preceded by short exposure treatment. These preliminary results indicate that N-Dox hold promise for melanoma treatment, reducing the minimum effective dose and perhaps a reduction in the cost of treatment.

Abstract Controlled release systems can modify the release rate of drugs and direct them to specific sites of action, making them more effective and/or reducing the adverse effects. The objective of this study was investigated, poly(β-hydroxybutyrate) (PHB) and poly(ε-caprolactone) (PCL) nanospheres to improve the delivery of Simvastatin (SIM). Nanospheres were prepared by the emulsion/evaporation technique of the solvent, varying the amount of SIM added. The SIM quantification was performed using a validated high-performance liquid chromatography method. The average diameter and PDI of formulations without SIM were lower 250 nm and 0.3, respectively. Nanospheres containing 30% of SIM showed values of 265 nm and 0.09, respectively. The average zeta potential was -31.8 mV, suggesting the predominance of repulsive forces that prevent aggregation. In vitro release suggest transport occurs by diffusion. Morphological analysis demonstrated spherical particles and rough surfaces. In conclusion, data suggest that PHB/PCL nanospheres are promising delivery systems to SIM.

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.