RESUMO
The post COVID-19 pandemic era has emerged with more efficient vaccines, all based on genetic materials. However, to expand the use of nucleic components as vaccines, a new generation of nanosystems particularly constructed to increase RNA/DNA stability, half-life and facilitate administration are still required. This review highlights novel developments in mRNA and pDNA vaccines formulated into nanostructures exclusively composed by biopolymeric materials. Recent advances suggest that a new generation of vaccines may arise by adapting the structural features of biopolymers with the effectiveness of nucleic acids. The advantages offered by biopolymers, such as increased stability and targeting ability may cause a revolution in the immunization field for offering promptly adaptable and effective formulations for worldwide distribution.
[Box: see text].
RESUMO
ABSTRACT: Chrysin flavonoid has been presented as having numerous and promising bioactive effects, such as antioxidant, anticonvulsant, antihypertensive, anti-inflammatory, antineoplastic, antihyperlipidemic, and antidepressant. However, one of the main challenges for advances in studies on the bioactivity of chrysin is its low bioavailability in humans. Thus, aiming to overcome this barrier, several studies have demonstrated the bioactive potential of capsules containing chrysin. The objective of this review was to present the main methodologies used for the encapsulation of chrysin, and its main biological effects demonstrated so far. Our intention is to offer ways to advancement of research in the area of flavonoid encapsulation. As for the encapsulation techniques, it was found that they are diverse, and the most recurrent encapsulating agents were PEG, PLGA polymers and their derivatives, in addition to other agents, such as PCL, albumin, lipids and chitosan.The bioactive effects of the capsules are also numerous, and anticarcinogenic effects are the most frequent, in addition to other effects such as antioxidant, antidiabetic, antimicrobial and neuroprotective. In conclusion, we verified a lack of use of green techniques for the encapsulation of chrysin, and the production of lipid-water emulsions and the dissolution of chrysin in ethanol seems to be alternatives in this regard. In addition, bioactive potential of these capsules can be evaluated in other experimental models, and should advance to clinical trials and application in food formulations.
RESUMO: O flavonoide crisina tem sido apresentado como tendo numerosos e promissores efeitos bioativos, como antioxidante, anticonvulsivante, anti-hipertensivo, anti-inflamatório, antineoplásico, anti-hiperlipidêmico e antidepressivo. No entanto, um dos principais desafios para o avanço dos estudos sobre a bioatividade da crisina é sua baixa biodisponibilidade em humanos. Assim, visando superar essa barreira, diversos estudos têm demonstrado o potencial bioativo de cápsulas contendo crisina. O objetivo desta revisão é apresentar as principais metodologias utilizadas para o encapsulamento da crisina e seus principais efeitos biológicos demonstrados até o momento. Nossa intenção é oferecer caminhos para o avanço das pesquisas na área de encapsulação de flavonoides. Quanto às técnicas de encapsulamento, verificou-se que são diversas, e os agentes encapsulantes mais recorrentes são os polímeros PEG, PLGA e seus derivados, além de outros agentes como PCL, albumina, lipídeos e quitosana. Os efeitos bioativos das cápsulas também são numerosos, sendo os efeitos anticarcinogênicos os mais frequentes, além de outros efeitos como antioxidante, antidiabético, antimicrobiano e neuroprotetor. Em conclusão, verificamos a falta de utilização de técnicas verdes para o encapsulamento de crisina, e a produção de emulsões lipídeo-água e dissolução da crisina em etanol parecem ser alternativas neste aspecto. Além disso, o potencial bioativo destas cápsulas pode ainda ser avaliado em outros modelos experimentais, e deve-se avançar para ensaios clínicos e aplicação em formulações alimentícias.
RESUMO
Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανß3 y ανß5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.
RESUMO
This work proposes a combination of polyethylene glycol 400 (PEG) and trehalose as a surface modification approach to enhance PLGA-based nanoparticles as a drug carrier for neurons. PEG improves nanoparticles' hydrophilicity, and trehalose enhances the nanoparticle's cellular internalization by inducing a more auspicious microenvironment based on inhibiting cell surface receptor denaturation. To optimize the nanoprecipitation process, a central composite design was performed; nanoparticles were adsorbed with PEG and trehalose. PLGA nanoparticles with diameters smaller than 200 nm were produced, and the coating process did not considerably increase their size. Nanoparticles entrapped curcumin, and their release profile was determined. The nanoparticles presented a curcumin entrapment efficiency of over 40%, and coated nanoparticles reached 60% of curcumin release in two weeks. MTT tests and curcumin fluorescence, with confocal imaging, were used to assess nanoparticle cytotoxicity and cell internalization in SH-SY5Y cells. Free curcumin 80 µM depleted the cell survival to 13% at 72 h. Contrariwise, PEG:Trehalose-coated curcumin-loaded and non-loaded nanoparticles preserved cell survival at 76% and 79% under the same conditions, respectively. Cells incubated with 100 µM curcumin or curcumin nanoparticles for 1 h exhibited 13.4% and 14.84% of curcumin's fluorescence, respectively. Moreover, cells exposed to 100 µM curcumin in PEG:Trehalose-coated nanoparticles for 1 h presented 28% fluorescence. In conclusion, PEG:Trehalose-adsorbed nanoparticles smaller than 200 nm exhibited suitable neural cytotoxicity and increased cell internalization proficiency.
RESUMO
Introduction: More than 1.9 million new cases of colorectal cancer and 935,000 deaths were estimated to have occurred worldwide in 2020. Therapies for metastatic colorectal cancer include cytotoxic chemotherapy and targeted therapies in multiple lines of treatment. Nevertheless, the optimal use of these agents has not yet been resolved. Regorafenib (RGF) is an Food and Drug Administration (FDA)-authorized multikinase inhibitor indicated for patients with metastatic colorectal cancer, non-responding to priority lines of chemotherapy and immunotherapy. Nanoparticles have been used in specific applications, such as site-specific drug delivery systems, cancer therapy, and clinical bioanalytical diagnostics. C-X-C Chemokine receptor type 4 (CXCR4) is the most widely-expressed chemokine receptor in more than 23 human cancer types, including colorectal cancer. This research aimed to synthesize and preclinically evaluate a targeted nanosystem for colorectal cancer chemo-radiotherapy using RGF encapsulated in Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles coated with a CXCR4 ligand (CXCR4L) and 177Lu as a therapeutic ß-emitter. Methods: Empty PLGA and PLGA(RGF) nanoparticles were prepared using the microfluidic method, followed by the DOTA and CXCR4L functionalization and nanoparticle radiolabeling with 177Lu. The final nanosystem gave a particle size of 280 nm with a polydispersity index of 0.347. In vitro and in vivo toxicity effects were assessed using the HCT116 colorectal cancer cell line. Results: 177Lu-PLGA(RGF)-CXCR4L nanoparticles decreased cell viability and proliferation by inhibiting Erk and Akt phosphorylation and promoting apoptosis. Moreover, in vivo administration of 177Lu-PLGA(RGF)-CXCR4L significantly reduced tumor growth in an HCT116 colorectal cancer xenograft model. The biokinetic profile showed hepatic and renal elimination. Discussion: Data obtained in this research justify additional preclinical safety trials and the clinical evaluation of 177Lu-PLGA(RGF)-CXCR4L as a potential combined treatment of colorectal cancer.
RESUMO
Articular cartilage is a specialized tissue that provides a smooth surface for joint movement and load transmission. Unfortunately, it has limited regenerative capacity. Tissue engineering, combining different cell types, scaffolds, growth factors, and physical stimulation has become an alternative for repairing and regenerating articular cartilage. Dental Follicle Mesenchymal Stem Cells (DFMSCs) are attractive candidates for cartilage tissue engineering because of their ability to differentiate into chondrocytes, on the other hand, the polymers blend like Polycaprolactone (PCL) and Poly Lactic-co-Glycolic Acid (PLGA) have shown promise given their mechanical properties and biocompatibility. In this work, the physicochemical properties of polymer blends were evaluated by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) and were positive for both techniques. The DFMSCs demonstrated stemness by flow cytometry. The scaffold showed to be a non-toxic effect when we evaluated it with Alamar blue, and the samples were analyzed using SEM and phalloidin staining to evaluate cell adhesion to the scaffold. The synthesis of glycosaminoglycans was positive on the construct in vitro. Finally, the PCL/PLGA scaffold showed a better repair capacity than two commercial compounds, when tested in a chondral defect rat model. These results suggest that the PCL/PLGA (80:20) scaffold may be suitable for applications in the tissue engineering of articular hyaline cartilage.
RESUMO
Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and ß parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a ß value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and ß values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the ß parameter for determining the drug release mechanism.
Assuntos
Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Liberação Controlada de Fármacos , Sistemas de Liberação de MedicamentosRESUMO
The development of scaffolding obtained by electrospinning is widely used in tissue engineering due to porous and fibrous structures that can mimic the extracellular matrix. In this study, poly (lactic-co-glycolic acid) (PLGA)/collagen fibers were fabricated by electrospinning method and then evaluated in the cell adhesion and viability of human cervical carcinoma HeLa and NIH-3T3 fibroblast for potential application in tissue regeneration. Additionally, collagen release was assessed in NIH-3T3 fibroblasts. The fibrillar morphology of PLGA/collagen fibers was verified by scanning electron microscopy. The fiber diameter decreased in the fibers (PLGA/collagen) up to 0.6 µm. FT-IR spectroscopy and thermal analysis confirmed that both the electrospinning process and the blend with PLGA give structural stability to collagen. Incorporating collagen in the PLGA matrix promotes an increase in the material's rigidity, showing an increase in the elastic modulus (38%) and tensile strength (70%) compared to pure PLGA. PLGA and PLGA/collagen fibers were found to provide a suitable environment for the adhesion and growth of HeLa and NIH-3T3 cell lines as well as stimulate collagen release. We conclude that these scaffolds could be very effective as biocompatible materials for extracellular matrix regeneration, suggesting their potential applications in tissue bioengineering.
RESUMO
Hybrid scaffolds from natural and synthetic polymers have been widely used due to the complementary nature of their physical and biological properties. The aim of the present study, therefore, has been to analyzein vivoa bilayer scaffold of poly(lactide-co-glycolide)/fibrin electrospun membrane and fibrin hydrogel layer on a rat skin model. Fibroblasts were cultivated in the fibrin hydrogel layer and keratinocytes on the electrospun membrane to generate a skin substitute. The scaffolds without and with cells were tested in a full-thickness wound model in Wistar Kyoto rats. The histological results demonstrated that the scaffolds induced granulation tissue growth, collagen deposition and epithelial tissue remodeling. The wound-healing markers showed no difference in scaffolds when compared with the positive control. Activities of antioxidant enzymes were decreased concerning the positive and negative control. The findings suggest that the scaffolds contributed to the granulation tissue formation and the early collagen deposition, maintaining an anti-inflammatory microenvironment.
Assuntos
Hidrogéis , Alicerces Teciduais , Ratos , Animais , Fibrina , Colágeno/farmacologia , Polímeros , Engenharia Tecidual/métodosRESUMO
In previous work, we reported on the design of biodegradable rhein-loaded PLGA microparticles for the treatment of osteoarthritis. Considering that a formulation designed for intra-articular administration must meet sterility requirements to guarantee its safety, in this study the effect of gamma radiation sterilization on these microparticles was evaluated. The size, morphology, and surface characteristics of the microparticles and the encapsulation efficiency of rhein were not affected by the sterilization process. Although DSC and PXRD analyses suggested otherwise, rhein release profiles were not altered by gamma radiation. The release of rhein from the microparticles was fitted to a Gompertz model. In conclusion, the results of this study suggest that gamma radiation is a suitable method for the sterilization of rhein-loaded PLGA microparticles to enable their intra-articular administration in order to provide a therapeutic solution to patients suffering from chronic joint diseases.