RESUMO
The lack of in vivo studies on the delivery of doxorubicin within human skin, especially the absence of data on the doxorubicin diffusion coefficient, has made understanding its transdermal delivery kinetics challenging. In this study, as a first step, governing equations and finite element methods were employed to reproduce Franz diffusion cell experiment in human cadaver skin. The application of this experiment representative model with a fitting method resulted in approximate values for the diffusivity of doxorubicin across various skin layers. The estimated values were used later to conduct a comprehensive examination of doxorubicin administration for breast tumor treatments. In a 2D axisymmetric model using Fick's Law and then a microneedles array 3D model, crucial parameters effects on delivery efficiency were examined, such as the microneedle tip diameter, tip-to-tip distance, and tumor depth. As highlighted by the findings of this study, these parameters have an impact on the effectiveness of doxorubicin delivery for treating breast tumors. The focus of this research is on the potential of numerical methods in biomedical engineering, which addresses the urgent need for data on doxorubicin diffusion in human skin and offers valuable insights into optimizing drug delivery strategies for enhanced therapeutic outcomes.
Assuntos
Administração Cutânea , Neoplasias da Mama , Doxorrubicina , Sistemas de Liberação de Medicamentos , Agulhas , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Humanos , Neoplasias da Mama/tratamento farmacológico , Feminino , Análise de Elementos Finitos , Pele/metabolismo , Modelos Biológicos , DifusãoRESUMO
Antioxidant and cytocompatible chemically modified polysaccharides and their hydrogels were obtained by a biomimetic approach. For this purpose, carboxymethylpullulan grafted with ferulic acid (CMP-FA) was firstly synthesized with different substitution degrees (DSFA). Their hydrogels were secondly obtained by enzymatic cross-linking with laccase. Hydrogel swelling has been found dependent on both DSFA and media ionic strength. The CMP-FA antioxidant properties were evaluated by the DPPH method and ABTS assays. The DPPH radical scavenging effect was high for CMP-FA solutions (80% after 30â¯min) and lower for the corresponding hydrogels (70% after 7â¯h). The antibacterial properties of ferulic acid and CMP-FA derivatives were tested against Staphylococcus aureus but the minimal inhibitory concentration of CMP-FA was not reached in the range of concentrations studied. Finally the CMP-FA derivatives showed no cytotoxicity towards mouse fibroblast cells.
Assuntos
Antioxidantes/farmacologia , Ácidos Cumáricos/química , Glucanos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Linhagem Celular , Ácidos Cumáricos/farmacologia , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Glucanos/química , Concentração de Íons de Hidrogênio , Lacase/química , Camundongos , Testes de Sensibilidade Microbiana , Concentração Osmolar , Staphylococcus aureus/efeitos dos fármacosRESUMO
Aminoguaiacol, the aminated derivative of guaiacol, a natural phenolic compound, was chemically grafted onto a polysaccharide (carboxymethylpullulan, CMP) in the presence of the activator agent 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDCI). The grafted polysaccharides were characterized by FTIR and 1H NMR spectroscopy to confirm and quantify the grafting. All polysaccharide derivatives (grafting rates of aminoguaiacol between 16% and 58%) were soluble in water. Their physicochemical properties were studied in a dilute regime and a semidilute regime by light scattering, fluorescence, and rheology, showing associative properties with peculiar polysoap behavior. The antibacterial activities of the synthesized products against Staphyloccocus aureus were assessed using a counting method. The antioxidant activities of the derivatives were also highlighted using the α,α-diphenyl-ß-picrylhydrazyl (DPPH) method. Finally, the cytotoxicity of the derivatives was studied with fibroblast cells and they showed a very good cytocompatibility. Such polymers could be used to replace chemical preservatives in food and cosmetic aqueous formulations.