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1.
Coord Chem Rev ; 4722022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37600158

RESUMEN

Engineered nanostructures are materials with promising properties, enabled by precise design and fabrication, as well as size-dependent effects. Biomedical applications of nanomaterials in disease-specific prevention, diagnosis, treatment, and recovery monitoring require precise, specific, and sophisticated approaches to yield effective and long-lasting favorable outcomes for patients. In this regard, carbon nanofibers (CNFs) have been indentified due to their interesting properties, such as good mechanical strength, high electrical conductivity, and desirable morphological features. Broadly speaking, CNFs can be categorized as vapor-grown carbon nanofibers (VGCNFs) and carbonized CNFs (e.g., electrospun CNFs), which have distinct microstructure, morphologies, and physicochemical properties. In addition to their physicochemical properties, VGCNFs and electrospun CNFs have distinct performances in biomedicine and have their own pros and cons. Indeed, several review papers in the literature have summarized and discussed the different types of CNFs and their performances in the industrial, energy, and composites areas. Crucially however, there is room for a comprehensive review paper dealing with CNFs from a biomedical point of view. The present work therefore, explored various types of CNFs, their fabrication and surface modification methods, and their applications in the different branches of biomedical engineering.

2.
Environ Res ; 214(Pt 3): 113966, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35952738

RESUMEN

Alginate-grafted polyaniline (Alg-g-PANI) microparticles were synthesized through the grafting of aniline onto functionalized Alg followed by double crosslinking by glutaraldehyde and calcium chloride. The performance of the developed microparticles as adsorbent in simultaneous removal of malachite green (MG) and congo red (CR) dyes were examined by the batch method. Experimental parameters, including adsorbent amount, pH, initial dyes concentrations, and contact time were optimized. Langmuir and Freundlich adsorption models were employed to explore the equilibrium isotherm. As the Langmuir model results, the maximum adsorption capacities (Qm) of microparticles for the MG and CR dyes were obtained as 578.3 and 409.6 mgg-1, respectively. Adsorption kinetics for both dyes were well-fitted with the pseudo-second-order model that confirm the rate-limiting step might be the chemical adsorption. The adsorbent was regenerated via desorption process and was reusable five times without a substantial decrease in its adsorption efficacy in first three cycles. Adsorbent-dyes interactions were computationally evaluated using Gromacs package, and it was found that both MG and CR are able to interact strongly with the adsorbent. In accordance with experimental results, simulation data revealed that MG can be removed more efficiently than those of the CR. As the experimental results, we could conclude that the synthesized Alg-g-PANI microparticles can be used as a nature-inspired adsorbent for simultaneous removals of CR and MG dyes.


Asunto(s)
Colorantes , Contaminantes Químicos del Agua , Adsorción , Aniones , Cationes , Rojo Congo , Concentración de Iones de Hidrógeno , Cinética , Contaminantes Químicos del Agua/análisis
3.
Drug Dev Ind Pharm ; 47(7): 1166-1174, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34590962

RESUMEN

A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for 'smart' treatment of cancer by chemo/hyperthermia approach. For this objective, Fe3O4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N,N'-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe3O4@P(DMAEMA-co-MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.


Asunto(s)
Antineoplásicos , Hipertermia Inducida , Nanopartículas , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Fenómenos Magnéticos
4.
Nanomedicine ; 24: 102149, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31927133

RESUMEN

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence, development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis. According to our overview of the current literature, AD is a multi-factorial disorder with various pathogenic trajectories; hence, a multifunctional strategy to create effective neuroprotective agents is required to treat this disorder.


Asunto(s)
Enfermedad de Alzheimer/patología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Enfermedades Neurodegenerativas/patología , Enfermedad de Alzheimer/terapia , Animales , Humanos , Enfermedades Neurodegenerativas/terapia
5.
Drug Dev Ind Pharm ; 46(11): 1832-1843, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32897756

RESUMEN

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly(N-isopropylacrylamide-block-acrylic acid) (HS-PNIPAAm-b-PAA) onto Fe3O4@Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe3O4@Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm-b-PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe3O4@Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe3O4@Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe3O4@Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe3O4 nanomaterials in its structure.


Asunto(s)
Hipertermia Inducida , Nanopartículas del Metal , Nanopartículas , Neoplasias , Doxorrubicina/química , Doxorrubicina/farmacología , Oro , Humanos , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica
6.
Sci Rep ; 14(1): 10418, 2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710793

RESUMEN

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.


Asunto(s)
Antibacterianos , Sistemas de Liberación de Medicamentos , Membranas Artificiales , Polímeros , Dióxido de Silicio , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Dióxido de Silicio/química , Polímeros/química , Porosidad , Sulfonas/química , Sulfonas/administración & dosificación , Liberación de Fármacos , Animales , Azitromicina/administración & dosificación , Azitromicina/farmacocinética , Azitromicina/química , Azitromicina/farmacología , Humanos
7.
Sci Rep ; 14(1): 6398, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493249

RESUMEN

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33's protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.


Asunto(s)
Queso , Neoplasias de la Boca , Probióticos , Humanos , Animales , Lactobacillus , Leche , Células CACO-2 , Yogur , Probióticos/farmacología , Antibacterianos/farmacología
8.
Int J Biol Macromol ; 231: 123333, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36682661

RESUMEN

Water pollution is increasing significantly owing to industrialization and population growth that lead to serious environmental and health issues. Therefore, the design and development of more effective wastewater treatment approaches are necessary due to a significant upsurge in demand for freshwater. More recently, metal-organic frameworks (MOFs) have attracted attention in environmental science owing to their tunable porosity, unique structure, flexibility, and various composition. Despite these attractive advantages, some drawbacks, including intrinsic fragility, unsatisfied processability, dust formation, and poor reusability, have greatly limited their applications. Therefore, MOFs are often designed as supported-based MOFs (e.g., MOFs-coated composites) or 3D structured composites, such as MOFs-based hydrogels. MOFs-based hydrogels are excellent candidates in the sorption process because of their appropriate adsorption capacity, porous structure, good mechanical properties, durability as well as biodegradable features. In this review, the removal of different pollutants (e.g., synthetic dyes, phosphates, heavy metals, antibiotics, and some organic compounds) from aqueous media has been studied by the adsorption process using MOFs-based hydrogels. The important advancements in the fabrication of MOFs-based hydrogels and their capacities in the adsorption of pollutants under experimental conditions have been discussed. Finally, problems and future perspectives on the adsorption process using MOFs-based hydrogels have been investigated.


Asunto(s)
Contaminantes Ambientales , Estructuras Metalorgánicas , Metales Pesados , Contaminantes Ambientales/química , Estructuras Metalorgánicas/química , Adsorción , Metales Pesados/química , Contaminación del Agua
9.
Int J Biol Macromol ; 249: 125991, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37499719

RESUMEN

Novel electrically conductive nanofibrous scaffolds were designed and fabricated through the grafting of aniline monomer onto a phenylamine-functionalized alginate (Alg-NH2) followed by electrospinning with poly(vinyl alcohol) (PVA). Performance of the prepared scaffolds in bone tissue engineering (TE) were studied in terms of physicochemical (e.g., conductivity, electroactivity, morphology, hydrophilicity, water uptake, and mechanical) and biological (cytocompatibility, in vitro biodegradability, cells attachment and proliferation, hemolysis, and protein adsorption) properties. The contact angles of the scaffolds with water drop were obtained about 50 to 60° that confirmed their excellent hydrophilicities for TE applications. Three dimensional (3D), inter-connected and uniform porous structures of the scaffolds without any bead formation was confirmed by scanning electron microscopy (SEM). Electrical conductivities of the fabricated scaffolds were obtained as 1.5 × 10-3 and 2.7 × 10-3 Scm-1. MTT assay results revealed that the scaffolds have acceptable cytocompatibilities and can enhance the cells adhesion as well as proliferation, which approved their potential for TE applications. Hemolysis rate of the developed scaffolds were quantified <2 % even at high concentration (200 µgmL-1) of samples that approved their hemocompatibilities. The scaffolds were also exhibited acceptable protein adsorption capacities (65 and 68 µgmg-1). As numerous experimental results, the developed scaffolds have acceptable potential for bone TE.


Asunto(s)
Nanofibras , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Nanofibras/química , Alginatos , Biomimética , Hemólisis , Agua , Proliferación Celular
10.
Biomed Pharmacother ; 166: 115408, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37651798

RESUMEN

Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed.


Asunto(s)
Enfermedad de Parkinson , Humanos , Proteolisis , Enfermedad de Parkinson/tratamiento farmacológico , Quimera Dirigida a la Proteólisis
11.
Int J Biol Macromol ; 249: 126041, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37516227

RESUMEN

As pivotal role of scaffold in tissue engineering (TE), the aim of present study was to design and development of extracellular matrix (ECM)-mimetic electrically conductive nanofibrous scaffolds composed of polyaniline-grafted tragacanth gum (TG-g-PANI) and poly(vinyl alcohol) (PVA) with different PANI content for skin tissue engineering (STE) application. The fabricated scaffolds were preliminary evaluated in terms of some physicochemical and biological properties. Cytocompatibility and cells proliferation properties of the scaffolds were examined with the well-known MTT assay, and it was found that the developed scaffolds have proper cytocompatibilities and can enhances the mouse fibroblast L929 cells adhesion as well as proliferation, which confirm their potential for STE applications. Hemocompatibility assay revealed that the hemolysis rate of the fabricated scaffolds were <2 % even at a relatively high concentration (200 µgmL-1) of samples, therefore, these scaffolds can be considered as safe. Human serum albumin (HSA) protein adsorption capacities of the fabricated scaffolds were quantified as 42 and 49 µgmg-1 that represent suitable values for a successful TE. Overall, the fabricated scaffold with 20 wt% of TG-g-PANI showed higher potential in both physicochemical and biological features than scaffold with 30 wt% of mentioned copolymer for STE application.


Asunto(s)
Nanofibras , Tragacanto , Ratones , Animales , Humanos , Ingeniería de Tejidos , Alcohol Polivinílico/química , Andamios del Tejido/química , Tragacanto/química , Nanofibras/química , Poliésteres/química , Matriz Extracelular
12.
ACS Omega ; 8(1): 771-781, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36643496

RESUMEN

Ischemic stroke accompanies oxidative stress and cell death in the cerebral tissue. The microRNA miR-34a plays a pivotal role in this molecular pathology. This study presents the rational repositioning of aminoglycosidic antibiotics as miR-34a antagonists in order to assess their efficiency in protecting the PC12 stroke model cells from oxidative stress occurring under cerebral ischemic conditions. A library of 29 amino-sugar compounds were screened against anticipated structural models of miR-34a through molecular docking. MiR-ligand interactions were mechanistically studied by molecular dynamics simulations and free-energy calculations. Cultured PC12 cells were treated by H2O2 alone or in combination with gentamycin and neomycin as selected drugs. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and annexin V-FITC/propidium iodate (PI) double staining assays, respectively. The expression levels of key factors involved in cell proliferation, oxidative stress, and apoptosis in treated PC12 cells were measured through a quantitative real-time polymerase chain reaction and flow cytometric annexin V-FITC/PI double staining assays. A stable and energetically favorable binding was observed for miR-34a with gentamycin and neomycin. Gentamycin pretreatments followed by H2O2 oxidative injury led to increased cell viability and protected PC12 cells against H2O2-induced apoptotic events. This study will help in further understanding how the suppression of miR-34a in neural tissue affects the cell viability upon stroke.

13.
Int J Biol Macromol ; 253(Pt 6): 127214, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37797855

RESUMEN

A novel strategy was designed and developed based of horseradish peroxidase (HRP)-mediated crosslinking of tyramine-functionalized starch (Tyr-St), tannic acid (TA) and phenolated-magnetic nanoparticles (Fe3O4-PhOH NPs), and simultaneous loading of doxorubicin hydrochloride (Dox) to afford a pH-responsive magnetic hydrogel-based drug delivery system (DDS) for synergistic in vitro chemo/hyperthermia therapy of human breast cancer (MCF-7) cells. The developed St-g-PTA/Fe3O4 magnetic hydrogel showed porous micro-structure with saturation magnetization (δs) value of 19.2 emu g-1 for Fe3O4 NPs content of ∼7.4 wt%. The pore sizes of the St-g-PTA/Fe3O4 hydrogel was calculated to be 2400 ± 200 nm-2. In vitro drug release experiments exhibited the developed DDS has pH-dependent drug release behavior, while at physiological pH (7.4) released only 30 % of the loaded drug after 100 h. Human serum albumin (HSA) adsorption capacities of the synthesized St/Fe3O4 and St-g-PTA/Fe3O4 magnetic hydrogels were obtained as 86 ± 2.2 and 77 ± 1.9 µgmg-1, respectively. The well-known MTT-assay approved the cytocompatibility of the developed St-g-PTA/Fe3O4 hydrogel, while the Dox-loaded system exhibited higher anti-cancer activity than those of the free Dox as verified by MTT-assay, and optical as well as florescent microscopies imaging. The synergistic chemo/hyperthermia therapy effect was also verified for the developed St-g-PTA/Fe3O4-Dox via hot water approach.


Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Hidrogeles , Almidón , Doxorrubicina/química , Hipertermia Inducida/métodos , Fenómenos Magnéticos , Liberación de Fármacos
14.
Int J Biol Macromol ; 253(Pt 6): 127297, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37813210

RESUMEN

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca2+. The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings.


Asunto(s)
Quitosano , Hidrogeles , Hidrogeles/farmacología , Hidrogeles/química , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Alginatos/química , Vendajes
15.
RSC Adv ; 13(49): 34587-34597, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38024994

RESUMEN

The anticancer properties of curcumin have been broadly examined in several shapes, such as nanoparticles and nanocomposite structures. Despite its benefits, curcumin also has some disadvantages, including rapid metabolism, poor absorption, and rapid systemic excretion. Therefore, numerous strategies have been used to increase curcumin's bioavailability. One of these approaches is the use of porous particles like aerogels as drug carriers. Aerogels are special due to their peculiar physical structure. They have a high specific surface area, a significant amount of porosity, and a solid composition, which make them a good choice for drug delivery systems. In the present study, a pH-sensitive aerogel was constructed and evaluated for targeted drug delivery of curcumin to colon cancer. To control the release of curcumin, trehalose was used as a coating agent, and PLP (poly(l-lysine isophthalamide)) was used as a targeted drug delivery agent. PLP is a pseudo-peptidic polymer that increases the cell permeability. In order to investigate and compare the synthesized aerogel before and after loading curcumin and coating with trehalose, physicochemical characterization analyses were performed. Finally, the efficacy of the final formulation was evaluated on HT29 colon cells using the cell bioavailability test. The results indicated the successful synthesis of the aerogel with porous structure with solitary cavities. The trehalose coating performed well, preventing drug release at lower pH but allowing the drug to be released at its intended site. The designed curcumin-loaded porous particles functionalized with PLP showed significant efficacy due to increasing penetration of curcumin into cells, and has potential for use as a new drug carrier with dual effectivity in cancer therapy.

16.
Eur J Med Chem ; 260: 115765, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37659194

RESUMEN

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.


Asunto(s)
Descubrimiento de Drogas , Procesamiento Proteico-Postraduccional , Proteolisis , Fosforilación , Ubiquitinación , Quimera Dirigida a la Proteólisis
17.
Int J Biol Macromol ; 241: 124529, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37085077

RESUMEN

The use of hydrogel dressings has become increasingly popular as a scaffold for skin tissue engineering. Herein, we have developed an innovative wound dressing using chitosan, fibrinogen, nisin, and EDTA as an effective antibacterial scaffold for wound treatment. The structural and functional characteristics of the hydrogel, including morphology, mechanical strength, drug encapsulation and release, swelling behaviors, blood coagulation, cytotoxicity, and antibacterial activity, were studied. Spectroscopic studies indicated that the attachment of chitosan to fibrinogen is associated with minimal change in its secondary structure; subsequently, at higher temperatures, it is expected to preserve fibrinogen's conformational stability. Mechanical and blood coagulation analyses indicated that the incorporation of fibrinogen into the hydrogel resulted in accelerated clotting and enhanced mechanical properties. Our cell studies showed biocompatibility and non-toxicity of the hydrogel along with the promotion of cell migration. In addition, the prepared hydrogel indicated an antibacterial behavior against both Gram-positive and Gram-negative bacteria. Interestingly, the in vivo data revealed enhanced tissue regeneration and recovery within 17 days in the studied animals. Taken together, the results obtained from in vitro and histological assessments indicate that this innovatively designed hydrogel shows good potential as a candidate for wound healing.


Asunto(s)
Antibacterianos , Quitosano , Animales , Antibacterianos/farmacología , Antibacterianos/química , Hidrogeles/farmacología , Hidrogeles/química , Quitosano/farmacología , Quitosano/química , Bacterias Gramnegativas , Bacterias Grampositivas , Cicatrización de Heridas , Vendajes , Coagulación Sanguínea , Fibrinógeno
18.
J Drug Target ; 30(3): 233-243, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34415800

RESUMEN

As a non-invasive method of local and systemic drug delivery, the administration of active pharmaceutical ingredients (APIs) via the pulmonary route represents an ideal approach for the therapeutic treatment of pulmonary diseases. The pulmonary route provides a number of advantages, including the rapid absorption which results from a high level of vascularisation over a large surface area and the successful avoidance of first-pass metabolism. Aerosolization of nanoparticles (NPs) is presently under extensive investigation and exhibits a high potential for targeted delivery of therapeutic agents for the treatment of a wide range of diseases. NPs need to possess specific characteristics to facilitate their transport along the pulmonary tract and appropriately overcome the barriers presented by the pulmonary system. The most challenging aspect of delivering NP-based drugs via the pulmonary route is developing colloidal systems with the optimal physicochemical parameters for inhalation. The physiochemical properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been investigated as a template for the synthesis of NPs to assist in the formulation of virus-like particles (VLPs) for pharmaceutical delivery, vaccine production and diagnosis assays.


Asunto(s)
Antivirales/administración & dosificación , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Nanopartículas/administración & dosificación , SARS-CoV-2 , Administración por Inhalación , Humanos , Farmacología en Red
19.
Sci Rep ; 12(1): 7213, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-35508533

RESUMEN

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14-198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.


Asunto(s)
Hidrogeles , Nisina , Alginatos/química , Alginatos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Fibrinógeno/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Nisina/farmacología , Cicatrización de Heridas
20.
Tissue Eng Part B Rev ; 28(5): 1053-1066, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34696626

RESUMEN

Type 1 diabetes (T1D) is caused by low insulin production and chronic hyperglycemia due to destruction of pancreatic ß-cells. Cell transplantation is an attractive alternative approach compared to insulin injection. However, cell therapy has been limited by major challenges, including life-long requirement for immunosuppressive drugs to prevent host immune responses. Encapsulation of the transplanted cells can solve the problem of immune rejection, by providing a physical barrier between the transplanted cells and the recipient's immune cells. Despite current disputes in cell encapsulation approaches, thanks to recent advances in the fields of biomaterials and transplantation immunology, extensive effort has been dedicated to immunoengineering strategies, in combination with encapsulation technologies, to overcome the problem of host's immune responses. This review summarizes the most commonly used encapsulation and immunoengineering strategies combined with cell therapy, which have been applied as a novel approach to improve cell replacement therapies for management of T1D. Recent advances in the fields of biomaterial design, nanotechnology, as well as deeper knowledge about immune modulation had significantly improved cell encapsulation strategies. However, further progress requires combined application of novel immunoengineering approaches and islet/ß-cell transplantation. Impact statement Cell encapsulation shows promising potential in preventing host's immune responses and rejection of islets or ß-cells by providing a selectively permeable barrier between the host and the transplanted cells. Innovative materials, conformal nanocoatings, and immunomodulation have provided promising approaches in the field of encapsulation technology. Novel nanocarriers have been synthesized to release and deliver immunosuppressive agents to islets/ß-cells within the capsules in a controlled manner. The immunoengineering approach (immunosuppressive and immunomodulatory agents) could overcome the challenges of cell replacement therapy in type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Insulinas , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Materiales Biocompatibles , Cápsulas/metabolismo , Islotes Pancreáticos/metabolismo , Inmunosupresores/metabolismo , Insulinas/metabolismo
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