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1.
Small ; 20(25): e2307247, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38243871

RESUMEN

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.


Asunto(s)
Sistemas CRISPR-Cas , Lípidos , Morus , Nanopartículas , Hojas de la Planta , Nanopartículas/química , Hojas de la Planta/química , Animales , Administración Oral , Morus/química , Lípidos/química , Ratones , Enfermedades del Colon/terapia , Humanos , Masculino , Liposomas
2.
J Biomed Sci ; 31(1): 13, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38254117

RESUMEN

Cancer remains a serious burden in society and while the pace in the development of novel and more effective therapeutics is increasing, testing platforms that faithfully mimic the tumor microenvironment are lacking. With a clear shift from animal models to more complex in vitro 3D systems, spheroids emerge as strong options in this regard. Years of development have allowed spheroid-based models to better reproduce the biomechanical cues that are observed in the tumor-associated extracellular matrix (ECM) and cellular interactions that occur in both a cell-cell and cell-ECM manner. Here, we summarize some of the key cellular interactions that drive tumor development, progression and invasion, and how successfully are these interactions recapitulated in 3D spheroid models currently in use in the field. We finish by speculating on future advancements in the field and on how these can shape the relevance of spherical 3D models for tumor modelling.


Asunto(s)
Neoplasias , Animales , Comunicación Celular , Modelos Animales de Enfermedad , Matriz Extracelular , Microambiente Tumoral
3.
Biomacromolecules ; 25(3): 1592-1601, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38377534

RESUMEN

Spinal cord injuries (SCI) have devastating physical, psychological, and psychosocial consequences for patients. One challenge of nerve tissue repair is the lack of a natural extracellular matrix (ECM) that guides the regenerating axons. Hyaluronic acid (HA) is a major ECM component and plays a fundamental role in facilitating lesion healing. Herein, we developed HA-based adhesive hydrogels by modification of HA with dopamine, a mussel-inspired compound with excellent adhesive properties in an aqueous environment. The hydrogels were loaded with the anti-inflammatory drug ibuprofen and the response of neuronal cells (SH-SY5Y) was evaluated in terms of viability, morphology, and adhesion. The obtained results suggested that the developed materials can bridge lesion gaps, guide axonal growth, and simultaneously act as a vehicle for the delivery of bioactive compounds.


Asunto(s)
Neuroblastoma , Traumatismos de la Médula Espinal , Humanos , Ácido Hialurónico , Hidrogeles , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Neuronas/patología , Médula Espinal/patología
4.
J Nanobiotechnology ; 22(1): 4, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38169394

RESUMEN

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Morus , Nanopartículas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Hojas de la Planta
5.
Mar Drugs ; 22(2)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38393026

RESUMEN

Chondrosia reniformis is a collagen-rich marine sponge that is considered a sustainable and viable option for producing an alternative to mammalian-origin collagens. However, there is a lack of knowledge regarding the properties of collagen isolated from different sponge parts, namely the outer region, or cortex, (ectosome) and the inner region (choanosome), and how it affects the development of biomaterials. In this study, a brief histological analysis focusing on C. reniformis collagen spatial distribution and a comprehensive comparative analysis between collagen isolated from ectosome and choanosome are presented. The isolated collagen characterization was based on isolation yield, Fourier-transformed infrared spectroscopy (FTIR), circular dichroism (CD), SDS-PAGE, dot blot, and amino acid composition, as well as their cytocompatibility envisaging the development of future biomedical applications. An isolation yield of approximately 20% was similar for both sponge parts, as well as the FTIR, CD, and SDS-PAGE profiles, which demonstrated that both isolated collagens presented a high purity degree and preserved their triple helix and fibrillar conformation. Ectosome collagen had a higher OHpro content and possessed collagen type I and IV, while the choanosome was predominately constituted by collagen type IV. In vitro cytotoxicity assays using the L929 fibroblast cell line displayed a significant cytotoxic effect of choanosome collagen at 2 mg/mL, while ectosome collagen enhanced cell metabolism and proliferation, thus indicating the latter as being more suitable for the development of biomaterials. This research represents a unique comparative study of C. reniformis body parts, serving as a support for further establishing this marine sponge as a promising alternative collagen source for the future development of biomedical applications.


Asunto(s)
Micropartículas Derivadas de Células , Poríferos , Animales , Micropartículas Derivadas de Células/metabolismo , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/metabolismo , Poríferos/metabolismo , Colágeno/química , Colágeno Tipo I/metabolismo , Mamíferos/metabolismo
6.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732135

RESUMEN

Glioblastoma (GBM) is the most lethal and common malignant primary brain tumor in adults. An important feature that supports GBM aggressiveness is the unique composition of its extracellular matrix (ECM). Particularly, fibronectin plays an important role in cancer cell adhesion, differentiation, proliferation, and chemoresistance. Thus, herein, a hydrogel with mechanical properties compatible with the brain and the ability to disrupt the dynamic and reciprocal interaction between fibronectin and tumor cells was produced. High-molecular-weight hyaluronic acid (HMW-HA) functionalized with the inhibitory fibronectin peptide Arg-Gly-Asp-Ser (RGDS) was used to produce the polymeric matrix. Liposomes encapsulating doxorubicin (DOX) were also included in the hydrogel to kill GBM cells. The resulting hydrogel containing liposomes with therapeutic DOX concentrations presented rheological properties like a healthy brain. In vitro assays demonstrated that unmodified HMW-HA hydrogels only caused GBM cell killing after DOX incorporation. Conversely, RGDS-functionalized hydrogels displayed per se cytotoxicity. As GBM cells produce several proteolytic enzymes capable of disrupting the peptide-HA bond, we selected MMP-2 to illustrate this phenomenon. Therefore, RGDS internalization can induce GBM cell apoptosis. Importantly, RGDS-functionalized hydrogel incorporating DOX efficiently damaged GBM cells without affecting astrocyte viability, proving its safety. Overall, the results demonstrate the potential of the RGDS-functionalized hydrogel to develop safe and effective GBM treatments.


Asunto(s)
Doxorrubicina , Fibronectinas , Glioblastoma , Ácido Hialurónico , Hidrogeles , Oligopéptidos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Oligopéptidos/química , Oligopéptidos/farmacología , Fibronectinas/metabolismo , Fibronectinas/antagonistas & inhibidores , Hidrogeles/química , Línea Celular Tumoral , Ácido Hialurónico/química , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Liposomas/química , Apoptosis/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo
7.
Crit Rev Food Sci Nutr ; : 1-43, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36688280

RESUMEN

Global population growth tremendously impacts the global food industry, endangering food safety and quality. Mycotoxins, particularly Ochratoxin-A (OTA), emerge as a food chain production threat, since it is produced by fungus that contaminates different food species and products. Beyond this, OTA exhibits a possible human toxicological risk that can lead to carcinogenic and neurological diseases. A selective, sensitive, and reliable OTA biodetection approach is essential to ensure food safety. Current detection approaches rely on accurate and time-consuming laboratory techniques performed at the end of the food production process, or lateral-flow technologies that are rapid and on-site, but do not provide quantitative and precise OTA concentration measurements. Nanoengineered optical biosensors arise as an avant-garde solution, providing high sensing performance, and a fast and accurate OTA biodetection screening, which is attractive for the industrial market. This review core presents and discusses the recent advancements in optical OTA biosensing, considering engineered nanomaterials, optical transduction principle and biorecognition methodologies. Finally, the major challenges and future trends are discussed, and current patented OTA optical biosensors are emphasized for a particular promising detection method.

8.
J Surg Res ; 283: 632-639, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36446251

RESUMEN

INTRODUCTION: Human adipose tissue contains a heterogeneous and synergistic mixture of cells called stromal vascular fraction (SVF) with highly proliferative and angiogenic properties, conferring promising applicability in the field of regenerative medicine. This study aims to investigate if age, body mass index (BMI), history of obesity and massive weight loss, and harvest site are related to SVF cell marker expression. METHODS: A total of 26 samples of subcutaneous adipose tissue were harvested from patients admitted to the Plastic and Reconstructive department in University Hospital Center of São João, Porto, Portugal, for body contouring surgery. The percentage of cells expressing CD31, CD34, CD45, CD73, CD90, and CD105 was assessed and compared with patient's age, BMI, history of obesity and massive weight loss (ex-obese group), and harvest site. RESULTS: In the ex-obese group, a significantly higher number of cells expressing CD90 (P = 0.002) was found. BMI, harvest site, and age appear to have no association with SVF subpopulations. CONCLUSIONS: This study suggests that ex-obese patients have a higher percentage of SVF cells expressing CD90, which correlates with higher proliferative and angiogenic rates. The effect of former obesity and massive weight loss on the expression of CD90 is a new and relevant finding because it makes this population a suitable candidate for reconstructive and aesthetic surgery and other fields of regenerative medicine. The use of SVF appears also promising in older patients because no negative correlation between increasing age and different cell markers expression was found.


Asunto(s)
Tejido Adiposo , Fracción Vascular Estromal , Humanos , Anciano , Obesidad/metabolismo , Grasa Subcutánea , Células del Estroma , Diferenciación Celular , Células Cultivadas
9.
Cell Mol Life Sci ; 79(3): 135, 2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35179655

RESUMEN

Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+ stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+ stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA. The CD133+ tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity.


Asunto(s)
Resistencia a Antineoplásicos , Metiltransferasas/metabolismo , Células Madre Neoplásicas/patología , Oxaliplatino/farmacología , Poli(ADP-Ribosa) Polimerasa-1/genética , Estabilidad del ARN , Neoplasias Gástricas/tratamiento farmacológico , Antígeno AC133 , Animales , Antineoplásicos/farmacología , Apoptosis , Proliferación Celular , Niño , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Metiltransferasas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasa-1/química , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Pronóstico , ARN Mensajero , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Mar Drugs ; 21(2)2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36827098

RESUMEN

The industrial processing of fish for food purposes also generates a considerable number of by-products such as viscera, bones, scales, and skin. From a value-added perspective, fish by-products can act also as raw materials, especially because of their collagen content (particularly in fish skin). Interestingly, the potential of marine collagen for cosmetic applications is enormous and, remarkably, the extraction of this protein from fish skins has been established for different species. Using this approach, we investigated the integration of marine collagen (COLRp_I) extracted from the skin of the Greenland halibut as an active ingredient in a cosmetic hydrogel formulation. In this study, extracts of marine collagen at concentrations up to 10 mg/mL showed a non-cytotoxic effect when cultured with fibroblast cells for 3 days. In addition, marine collagen extract, when incorporated into a cosmetic hydrogel formulation, met criterion A of ISO 11930:2019 regarding the efficacy of the preservative system (challenge test). In addition, the cosmetic formulations based on marine collagen at dosages of 0.1, 0.25 and 0.5% were tested in a clinical study on the skin of the forearms of 23 healthy volunteers, showing a sightly hydration effect, suggesting its potential for beauty applications. Moreover, this work illustrates that the circular economy concept applied to the fish processing industry can represent important benefits, at innovation, environmental and economic levels.


Asunto(s)
Cosméticos , Lenguado , Animales , Groenlandia , Piel/metabolismo , Colágeno/metabolismo , Peces
11.
Mar Drugs ; 21(2)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-36827137

RESUMEN

Arthropods, the largest animal phylum, including insects, spiders and crustaceans, are characterized by their bodies being covered primarily in chitin. Besides being a source of this biopolymer, crustaceans have also attracted attention from biotechnology given their cuticles' remarkable and diverse mechanical properties. The goose barnacle, Pollicipes pollicipes, is a sessile crustacean characterized by their body parts covered with calcified plates and a peduncle attached to a substrate covered with a cuticle. In this work, the composition and structure of these plates and cuticle were characterized. The morphology of the tergum plate revealed a compact homogeneous structure of calcium carbonate, a typical composition among marine invertebrate hard structures. The cuticle consisted of an outer zone covered with scales and an inner homogenous zone, predominantly organic, composed of successive layers parallel to the surface. The scales are similar to the tergum plate and are arranged in parallel and oriented semi-vertically. Structural and biochemical characterization confirmed a bulk composition of ɑ-chitin and suggested the presence of elastin-based proteins and collagen. The mechanical properties of the cuticle showed that the stiffness values are within the range of values described in elastomers and soft crustacean cuticles resulting from molting. The removal of calcified components exposed round holes, detailed the structure of the lamina, and changed the protein properties, increasing the rigidity of the material. This flexible cuticle, predominantly inorganic, can provide bioinspiration for developing biocompatible and mechanically suitable biomaterials for diverse applications, including in tissue engineering approaches.


Asunto(s)
Artrópodos , Thoracica , Animales , Thoracica/metabolismo , Quitina/química
12.
Mar Drugs ; 21(7)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37504925

RESUMEN

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.


Asunto(s)
Quitosano , Emulsiones , Diclofenaco , Aceites de Plantas/química , Aceite de Coco/química
13.
Mar Drugs ; 21(5)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37233496

RESUMEN

Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus, FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8-2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.


Asunto(s)
Fucus , Ratones , Animales , Lipopolisacáridos , Polisacáridos/farmacología , Citocinas
14.
Pediatr Surg Int ; 40(1): 7, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-37999778

RESUMEN

BACKGROUND: Patch repair of congenital diaphragmatic hernia (CDH) using Gore-Tex® is associated with infection, adhesions, hernia recurrence, long-term musculoskeletal sequels and poor tissue regeneration. To overcome these limitations, the performance of two novel biodegradable membranes was tested to repair CDH in a growing pig model. METHODS: Twelve male pigs were randomly assigned to 3 different groups of 4 animals each, determined by the type of patch used during thoracoscopic diaphragmatic hernia repair (Gore-Tex®, polycaprolactone electrospun membrane-PCLem, and decellularized human chorion membrane-dHCM). After 7 weeks, all animals were euthanized, followed by necropsy for diaphragmatic evaluation and histological analysis. RESULTS: Thoracoscopic defect creation and diaphragmatic repair were performed without any technical difficulty in all groups. However, hernia recurrence rate was 0% in Gore-Tex®, 50% in PCLem and 100% in dHCM groups. At euthanasia, Gore-Tex® patches appeared virtually unchanged and covered with a fibrotic capsule, while PCLem and dHCM patches were replaced by either floppy connective tissue or vascularized and floppy regenerated membranous tissue, respectively. CONCLUSION: Gore-Tex® was associated with a higher survival rate and lower recurrence. Nevertheless, the proposed biodegradable membranes were associated with better tissue integration when compared with Gore-Tex®.


Asunto(s)
Hernias Diafragmáticas Congénitas , Politetrafluoroetileno , Animales , Masculino , Diafragma , Hernias Diafragmáticas Congénitas/cirugía , Herniorrafia , Porcinos
15.
Int J Mol Sci ; 25(1)2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38203483

RESUMEN

Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPs' uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Poliésteres , Polietilenglicoles , Humanos , Femenino , Transporte Biológico , Sistemas de Liberación de Medicamentos , Neoplasias de la Mama/tratamiento farmacológico
16.
Molecules ; 28(3)2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36770658

RESUMEN

The demand for bio-based and safer composite materials is increasing due to the growth of the industry, human population, and environmental concerns. In this framework, sustainable and safer cork-polymer composites (CPC), based on green low-density polyethylene (LDPE) were developed using melt-based technologies. Chitosan and polyethylene-graft-maleic anhydride (PE-g-MA) were employed to enhance the CPC's properties. The morphology, wettability, mechanical, thermal, and antibacterial properties of the CPC against Pseudomonas putida (P. putida) and Staphylococcus aureus (S. aureus) were examined. The CPC showed improved stiffness when compared with that of the LDPE matrix, preferably when combined with chitosan and PE-g-MA (5 wt. %), reinforcing the stiffness (58.8%) and the strength (66.7%). Chitosan also increased the composite stiffness and strength, as well as reduced the surface hydrophilicity. The CPCs' antibacterial activity revealed that cork significantly reduces the biofilm on the polymer matrix. The highest biofilm reduction was found with CPC containing cork and 5 wt. % chitosan for both P. putida (54% reduction) and S. aureus (36% reduction), confirming their potential to extend the lifespan of products for packaging and healthcare, among other applications. This work leads to the understanding of the factors that influence biofilm formation in cork composites and provides a strategy to reinforce their behavior using chitosan.


Asunto(s)
Incrustaciones Biológicas , Quitosano , Humanos , Quitosano/farmacología , Polietileno , Incrustaciones Biológicas/prevención & control , Staphylococcus aureus , Antibacterianos/farmacología , Polímeros
17.
Molecules ; 28(8)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37110628

RESUMEN

Collagen is the major structural protein in extracellular matrix present in connective tissues, including skin, being considered a promising material for skin regeneration. Marine organisms have been attracting interest amongst the industry as an alternative collagen source. In the present work, Atlantic codfish skin collagen was analyzed, to evaluate its potential for skincare. The collagen was extracted from two different skin batches (food industry by-product) using acetic acid (ASColl), confirming the method reproducibility since no significant yield differences were observed. The extracts characterization confirmed a profile compatible with type I collagen, without significant differences between batches or with bovine skin collagen (a reference material in biomedicine). Thermal analyses suggested ASColl's native structure loss at 25 °C, and an inferior thermal stability to bovine skin collagen. No cytotoxicity was found for ASColl up to 10 mg/mL in keratinocytes (HaCaT cells). ASColl was used to develop membranes, which revealed smooth surfaces without significative morphological or biodegradability differences between batches. Their water absorption capacity and water contact angle indicated a hydrophilic feature. The metabolic activity and proliferation of HaCaT were improved by the membranes. Hence, ASColl membranes exhibited attractive characteristics to be applied in the biomedical and cosmeceutical field envisaging skincare.


Asunto(s)
Gadiformes , Gadus morhua , Animales , Bovinos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/análisis , Gadus morhua/metabolismo , Reproducibilidad de los Resultados , Piel/metabolismo , Colágeno/química , Gadiformes/metabolismo
18.
Molecules ; 28(11)2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37298999

RESUMEN

Current management for diabetes has stimulated the development of versatile 3D-based hydrogels as in vitro platforms for insulin release and as support for the encapsulation of pancreatic cells and islets of Langerhans. This work aimed to create agarose/fucoidan hydrogels to encapsulate pancreatic cells as a potential biomaterial for diabetes therapeutics. The hydrogels were produced by combining fucoidan (Fu) and agarose (Aga), marine polysaccharides derived from the cell wall of brown and red seaweeds, respectively, and a thermal gelation process. The agarose/fucoidan (AgaFu) blended hydrogels were obtained by dissolving Aga in 3 or 5 wt % Fu aqueous solutions to obtain different proportions (4:10; 5:10, and 7:10 wt). The rheological tests on hydrogels revealed a non-Newtonian and viscoelastic behavior, while the characterization confirmed the presence of the two polymers in the structure of the hydrogels. In addition, the mechanical behavior showed that increasing Aga concentrations resulted in hydrogels with higher Young's modulus. Further, the ability of the developed materials to sustain the viability of human pancreatic cells was assessed by encapsulation of the 1.1B4HP cell line for up to 7 days. The biological assessment of the hydrogels revealed that cultured pancreatic beta cells tended to self-organize and form pseudo-islets during the period studied.


Asunto(s)
Diabetes Mellitus , Hidrogeles , Humanos , Sefarosa/química , Hidrogeles/farmacología , Hidrogeles/química , Polisacáridos/farmacología , Polisacáridos/química , Diabetes Mellitus/tratamiento farmacológico
19.
Biomacromolecules ; 23(6): 2415-2427, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35623028

RESUMEN

Metronidazole (MTZ) is a drug potentially used for the treatment of intestinal infections, namely, the ones caused by colorectal surgery. The traditional routes of administration decrease its local effectiveness and present off-site effects. To circumvent such limitations, herein a drug delivery system (DDS) based on MTZ-loaded nanoparticles (NPs) immobilized at the surface of electrospun fibrous meshes is proposed. MTZ at different concentrations (1, 2, 5, and 10 mg mL-1) was loaded into chitosan-sodium tripolyphosphate NPs. The MTZ loaded into NPs at the highest concentration showed a quick release in the first 12 h, followed by a gradual release. This DDS was not toxic to human colonic cells. When tested against different bacterial strains, a significant reduction of Escherichia coli and Staphylococcus aureus was observed, but no effect was found against Enterococcus faecalis. Therefore, this DDS offers high potential to locally prevent the occurrence of infections after colorectal anastomosis.


Asunto(s)
Quitosano , Neoplasias Colorrectales , Nanopartículas , Antibacterianos/farmacología , Bacterias , Quitosano/farmacología , Sistemas de Liberación de Medicamentos , Escherichia coli , Humanos , Metronidazol/farmacología , Virulencia
20.
Photochem Photobiol Sci ; 21(7): 1159-1173, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35366753

RESUMEN

Curcumin (Cur), a polyphenolic compound derived from Curcuma longa L., has garnered the attention of the scientific community due to its remarkable biological properties such as its potential as a photosensitizing agent for photodynamic therapy (PDT). However, due to its low solubility in aqueous media and instability at physiological and alkaline pH, Cur has struggled to find relevant clinical application. To tackle these shortcomings, two distinct Cur-based formulations based on either complexation with methyl-ß-cyclodextrin (MßCD), MßCDC-Cur, or dissolution in a choline chloride (ChCl): glycerol (Gly) deep eutectic solvent (DES), DES-Cur, were produced, physio-chemically characterized and compared regarding their potential as phototherapeutic agents for blue-light antimicrobial photodynamic therapy (aPDT) approaches. Both MßCD-Cur and DES-Cur were able to greatly enhance Cur solubility profile when compared to Cur powder. However, MßCD-Cur appears to hinder some of Cur's basal biological properties and possessed greater basal cytotoxicity towards L929 murine fibroblast cell line. Furthermore, MßCD-Cur was less photo-responsive when exposed to light which may hamper its application in blue-light aPDT approaches. In contrast, DES-Cur showed good biological properties and high photoresponsivity, displaying relevant phototoxicity against bacterial pathogens (≥ 99.9% bacterial reduction) while being better tolerated by L929 murine cells. Overall, this study found DES to be the more effective vehicle for Cur in terms of phototherapeutic potential which will serve as basis to develop novel platforms and approaches for blue-light aPDT targeting localized superficial infections.


Asunto(s)
Curcumina , Ciclodextrinas , Fotoquimioterapia , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Curcumina/química , Curcumina/farmacología , Disolventes Eutécticos Profundos , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico
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