RESUMO
Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.
Assuntos
Ouro , Nanofibras , Poliuretanos , Espécies Reativas de Oxigênio , Selênio , Cicatrização , Cicatrização/efeitos dos fármacos , Poliuretanos/química , Poliuretanos/farmacologia , Animais , Nanofibras/química , Selênio/química , Selênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ouro/química , Ouro/farmacologia , Ratos , Nanotubos/química , Antibacterianos/farmacologia , Antibacterianos/química , Desferroxamina/farmacologia , Desferroxamina/química , Ratos Sprague-Dawley , Humanos , Indometacina/farmacologia , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
The macrophages take significant roles in homeostasis, phagocytosis of pathogenic organisms, and modulation of host defense and inflammatory processes. In this study, the enantiomeric poly-D-lysine (PDL) and poly-L-lysine (PLL) were conjugated to gold nanorods (AuNRs) to study their influence on the polarization of macrophages. The AuNRs capped with cetyl trimethyl ammonium bromide (CTAB) (AuNRs@CTAB) exhibited larger toxicity to macrophages when their concentration was higher than 50 µg/ml, whereas the AuNRs@PDL and AuNRs@PLL showed neglectable toxicity at the same concentration compared with the control. The AuNRs@PDL and AuNRs@PLL were internalized into the macrophages with a higher value than the AuNRs@CTAB as revealed by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) characterization. Unlike the grafted PDL/PLL on flat substrates, the AuNRs@PDL and AuNRs@PLL were not able to polarize M0 macrophages to any other phenotype after internalization as confirmed by ELISA, flow cytometry, and fluorescence microscopy analysis. Nonetheless, the expression of M1 phenotype markers was reduced after the internalization of AuNRs@PDL and AuNRs@PLL by M1 macrophages. The assays of ELISA, flow cytometry, and reactive oxygen species levels exhibited decrease in inflammation of the M1 macrophages.
Assuntos
Ouro , Nanotubos , Ouro/química , Ouro/farmacologia , Macrófagos , Microscopia Eletrônica de Transmissão , Nanotubos/química , Polilisina/farmacologiaRESUMO
Tissue regeneration involves versatile types of cells. The accumulation and disorganized behaviors of undesired cells impair the natural healing process, leading to uncontrolled immune response, restenosis, and/or fibrosis. Cell-selective surfaces and interfaces can have specific and positive effects on desired types of cells, allowing tissue regeneration with restored structures and functions. This review outlines the importance of surfaces and interfaces of biomaterials with cell-selective properties. The chemical and biological cues including peptides, antibodies, and other molecules, physical cues such as topography and elasticity, and physiological cues referring mainly to interactions between cells-cells and cell-chemokines or cytokines are effective modulators for achieving cell selectivity upon being applied into the design of biomaterials. Cell-selective biomaterials have also shown practical significance in tissue regeneration, in particular for endothelialization, nerve regeneration, capture of stem cells, and regeneration of tissues of multiple structures and functions.
Assuntos
Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Animais , Anticorpos/química , Anticorpos/farmacologia , Materiais Biocompatíveis/farmacologia , Comunicação Celular , Endotélio Vascular/citologia , Humanos , Regeneração Nervosa , Peptídeos/química , Peptídeos/farmacologia , Regeneração , Células-Tronco/fisiologia , Propriedades de SuperfícieRESUMO
BACKGROUND: Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. RESULTS: Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. CONCLUSION: PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail.