RESUMO
Nanotechnology's potential in revolutionising cancer treatments is evident in targeted drug delivery systems (DDSs) engineered to optimise therapeutic efficacy and minimise toxicity. This study examines a novel nanocarrier constructed with carbon nano-onions (CNOs), engineered and evaluated for its ability to selectively target cancer cells overexpressing the hyaluronic acid receptor; CD44. Our results highlighted that the CNO-based nanocarrier coupled with hyaluronic acid as the targeting agent demonstrated effective uptake by CD44+ PANC-1 and MIA PaCa-2 cells, while avoiding CD44- Capan-1 cells. The CNO-based nanocarrier also exhibited excellent biocompatibility in all tested pancreatic ductal adenocarcinoma (PDAC) cells, as well as healthy cells. Notably, the CNO-based nanocarrier was successfully loaded with chemotherapeutic 4-(N)-acyl- sidechain-containing prodrugs derived from gemcitabine (GEM). These prodrugs alone exhibited remarkable efficacy in killing PDAC cells which are known to be GEM resistant, and their efficacy was amplified when combined with the CNO-based nanocarrier, particularly in targeting GEM-resistant CD44+ PDAC cells. These findings demonstrate the potential of CNOs as promising scaffolds in advancing targeted DDSs, signifying the translational potential of carbon nanoparticles for cancer therapy.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pró-Fármacos , Humanos , Gencitabina , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Cebolas , Ácido Hialurônico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Recently a new series of nitrooxy-acyl derivatives of salicylic acid (SA) was described presenting similar anti-inflammatory activities but reduced or no gastrotoxicity compared to aspirin. In this work, lipophilicity and permeability profiles of SA derivatives were performed to evaluate their ADME properties related to oral or transdermic delivery. All tested compounds showed potential good passive permeation through gastrointestinal track and also through percutaneous barrier which could be a way to avoid the first hepatic pass.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Aspirina/análogos & derivados , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Fenômenos Químicos , Avaliação Pré-Clínica de Medicamentos , Humanos , Absorção Intestinal , Membranas Artificiais , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacocinética , Permeabilidade , Potenciometria , Absorção CutâneaRESUMO
A new class of products in which the phenol group of salicylic acid is linked to alkanoyl moieties bearing nitrooxy functions has been synthesized and studied for their polyvalent actions. The products were stable in acid and neutral media, while they were hydrolyzed in human serum. Their half-lives were dependent upon the structure of alkanoyl moieties. The products showed anti-inflammatory activities similar to aspirin when tested in the carrageenan-induced paw edema assay in the rat. Interestingly, unlike aspirin, they showed reduced or no gastrotoxicity in a lesion model in rats at equimolar doses. A number of them were able to inhibit platelet aggregation induced by collagen in human platelet-rich plasma. All of the products were capable of relaxing rat aortic strips precontracted with phenylephrine in a concentration-dependent manner. Selected members of this new class of nonsteroidal anti-inflammatory drugs might represent possible safer alternatives to aspirin in different clinical settings.