RESUMO
Introduction: The use of chitosan in pharmaceutical formulations is an advantageous approach due to this compound intrinsic biodegradability and biocompatibility, as well as ready availability and low polymer cost. Methods: Herein, the naphthoquinones 3- chloromethylene-menadione (NQ1) and 2,3-dichloro-1,4-naphthoquinone (NQ2) were nanoencapsulated into chitosan (CNP) by the ionotropic gelatinization technique and characterized by DLS, FTIR, SEM, TGA and DSC, and their release profiles evaluated. The antimicrobial and wound healing activities were investigated. Results and Discussion: Homogeneous chitosan nanocapsulses of about 193 nm and Z potential ranging from +30.6 to +33.1 mV loaded with NQ1 (CNP-NQ1) or NQ2 (CNPQNQ2). With nanoencapsulation efficiencies of ≥ 96%, the solubility of naphthoquinones in aqueous environments was improved, making them suitable for biological system applications. The encapsulated naphthoquinones displayed a controlled release of approximately 80% for CNP-NQ1 and 90% for CNP-NQ2 over an 8 h period at 36°C. Both CNP-NQ1 and CNP-NQ2 retained the already established free naphthoquinone antimicrobial activity against two Staphylococcus aureus strains, Staphylococcus epidermidis, Streptococcus pyogenes and Pseudomonas aeruginosa. Although presenting low toxicity to healthy human cells, only CNP-NQ1 displayed therapeutic indices above 100 for S. aureus and S. epidermidis and above 27 for S. pyogenes and P. aeruginosa, allowing for safe use in human tissues. Furthermore, CNP-NQ1 did not impair the migration of human fibroblast cells in scratch assays, adding promising wound healing properties to this formulation. These findings emphasize that CNP-NQ1 may be useful in protecting injured skin tissue from bacterial contamination, avoiding skin infections not only by reducing bacterial loads but also by accelerating the healing process until complete dermal tissue recovery.
RESUMO
We developed a novel method for the synthesis of bis-naphthoquinones (BNQ), which are hybrids of lawsone (2-hydroxy-1,4-naphthoquinone) and 3-hydroxy-juglone (3,5-dihydroxy-1,4-naphthoquinone). The anticancer activity of three synthesized compounds, named 4 (RC10), 5 (RCDFC), and 6 (RCDOH) was evaluated in vitro against two metastatic prostate cancer (PCa) cell lines, DU145 and PC3, using MTT assays. We found that 4 (RC10) and 5 (RCDFC) induced cytotoxicity against DU145 and PC3 cells. Flow cytometry analysis revealed that these two compounds promoted cell cycle arrest in G1/S and G2/M phases, increased Sub-G1 peak and induced inhibition in cell viability. We also showed that these effects are cell-type context dependent and more selective for these tested PCa cells than for HUVEC non-tumor cells. The two BNQ compounds 4 (RC10) and 5 (RCDFC) displayed promising anticancer activity against the two tested metastatic PCa cell lines, DU145 and PC3. Their effects are mainly associated with inhibition of cell viability, possibly through apoptotic cell death, besides altering the SubG1, G1/S and G2/M phases of cell cycle. 5 (RCDFC) compound was found to be more selective than 4 (RC10), when comparing their cytotoxic effects in relation to HUVEC non-tumoral cells. Future work should also test these compounds in combination with other chemotherapeutic drugs to evaluate their effects on further sensitizing drug-resistant metastatic PCa cells.
