Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28.701
Filtrar
1.
J Environ Sci (China) ; 147: 359-369, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003053

RESUMO

Agricultural practices significantly contribute to greenhouse gas (GHG) emissions, necessitating cleaner production technologies to reduce environmental pressure and achieve sustainable maize production. Plastic film mulching is commonly used in the Loess Plateau region. Incorporating slow-release fertilizers as a replacement for urea within this practice can reduce nitrogen losses and enhance crop productivity. Combining these techniques represents a novel agricultural approach in semi-arid areas. However, the impact of this integration on soil carbon storage (SOCS), carbon footprint (CF), and economic benefits has received limited research attention. Therefore, we conducted an eight-year study (2015-2022) in the semi-arid northwestern region to quantify the effects of four treatments [urea supplied without plastic film mulching (CK-U), slow-release fertilizer supplied without plastic film mulching (CK-S), urea supplied with plastic film mulching (PM-U), and slow-release fertilizer supplied with plastic film mulching (PM-S)] on soil fertility, economic and environmental benefits. The results revealed that nitrogen fertilizer was the primary contributor to total GHG emissions (≥71.97%). Compared to other treatments, PM-S increased average grain yield by 12.01%-37.89%, water use efficiency by 9.19%-23.33%, nitrogen accumulation by 27.07%-66.19%, and net return by 6.21%-29.57%. Furthermore, PM-S decreased CF by 12.87%-44.31% and CF per net return by 14.25%-41.16%. After eight years, PM-S increased SOCS (0-40 cm) by 2.46%, while PM-U decreased it by 7.09%. These findings highlight the positive effects of PM-S on surface soil fertility, economic gains, and environmental benefits in spring maize production on the Loess Plateau, underscoring its potential for widespread adoption and application.


Assuntos
Agricultura , Pegada de Carbono , Fertilizantes , Plásticos , Zea mays , Zea mays/crescimento & desenvolvimento , Agricultura/métodos , China , Solo/química , Gases de Efeito Estufa/análise , Nitrogênio/análise
2.
Ocul Immunol Inflamm ; : 1-2, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008114

RESUMO

In their recent publication, the authors explored the preventive effect of gentamicin in the irrigating solution on endophthalmitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) after phacoemulsification with intraocular lens (IOL) implantation in rabbits. This letter commends the authors for their innovative approach and discusses the potential of chitosan-based intraocular lenses as a future solution for reducing the incidence of endophthalmitis. Chitosan's natural antibacterial properties, coupled with its capacity for sustained drug release and surface modification, make it a promising material for IOLs. This letter highlights recent advancements and suggests areas for further research to fully realize the potential of chitosan-based IOLs in ocular surgery.

3.
Environ Technol ; : 1-13, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955513

RESUMO

Pyrolysis is an effective process for disposing of municipal sewage sludge (SS). Plastics can affect the SS pyrolysis behaviour and pyrolysis products due to their low ash and high hydrocarbon ratio. The secondary pollutants from the pyrolysis process may also be affected. Therefore, polyethylene terephthalate (PET), a typical plastic, was chosen to investigate the release characteristics of pollutants containing nitrogen, sulphur, and chlorine via SS pyrolysis, and the changes of biochar to adsorb two typical heavy metals, Pb and Cu. The pyrolysis of PET plastics facilitates the migration of N toward solid and liquid-phase products, S and Cl to the gas-phase products via pyrolysis. Oxygenated compounds of pyrolytic volatiles decreased from 38.18% to 28.43%, concurrently promoting the formation of phenolic compounds. The co-pyrolysis improved the quality of biochar and the ability to adsorb Pb and Cu. This systematic study can provide some support for the further improvement of SS pyrolysis technology, and will also be beneficial for subsequent applications.

4.
Int J Biol Macromol ; : 133335, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955548

RESUMO

The use of essential oils is widespread in various fields such as pharmacy, pest control, and active packaging. However, their instability and short-term effects require methods to enhance their durability and effectiveness. Encapsulation in biopolymer matrices appears to be a promising approach due to the environmental safety and cost-effectiveness of such formulations. In this study, different oil-in-water emulsions were prepared by mixing chitosan-gelatin (C-G) or pectin-gelatin (P-G) solutions with lemongrass essential oil (LG). ZnO NPs were used as an additional active component. Encapsulation in biopolymer matrices resulted in stable emulsions with a significantly slower release of LG, and ZnO NPs further suppressed LG release, particularly in the P-G emulsion. They also contributed to the stability of the emulsions and a decrease in the average droplet size of LG. Furthermore, the presence of LG and ZnO NPs improved the smoothness of the films prepared from the emulsions and dispersions using the casting technique. SEM/EDS analysis confirmed the homogeneous distribution of ZnO NPs in both C-G and P-G films. By adjusting the type and content of the biopolymers and NPs, such emulsions could be effectively utilized in various applications where controlled release of active components is required.

5.
Trends Biotechnol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955569

RESUMO

3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure-property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies.

6.
Int J Biol Macromol ; 275(Pt 1): 133557, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955293

RESUMO

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

7.
Crit Rev Food Sci Nutr ; : 1-17, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38965668

RESUMO

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

8.
J Biomater Sci Polym Ed ; : 1-16, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965881

RESUMO

In this study, a novel bio-composite material that allow sustained release of plant derived antimicrobial compound was developed for the biomedical applications to prevent the infections caused by microorganisms resistant to commercial antimicrobials agents. With this aim, bacterial cellulose (BC)-p(HEMA) nanocomposite film that imprinted with eugenol (EU) via metal chelated monomer, MAH was prepared. Firstly, characterization studies were utilized by FTIR, SEM and BET analysis. Then antimicrobial assays, drug release studies and in vitro cytotoxicity test were performed. A significant antimicrobial effect against both Gram (+) Staphylococcus aureus and Gram (-) Escherichia coli bacteria and a yeast Candida albicans were observed even in low exposure time periods. When antimicrobial effect of EU compared with commercially used agents, both antifungal and antibacterial activity of EU were found to be higher. Then, sustained drug release studies showed that approximately 55% of EU was released up to 50 h. This result proved the achievement of the molecular imprinting for an immobilization of molecules that desired to release on an area in a long-time interval. Finally, the in vitro cytotoxicity experiment performed with the mouse L929 cell line determined that the synthesized EU-imprinted BC nanocomposite was biocompatible.

9.
Int J Pharm ; 661: 124407, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955239

RESUMO

This study aimed to develop a 3D-printed fixed-dose combination tablet featuring differential release of two drugs using double-melt extrusion (DME). The hot-melt extrusion (HME) process was divided into two steps to manufacture a single filament containing the two drugs. In Step I, a sustained-release matrix of acetaminophen (AAP) was obtained through HME at 190 °C using Eudragit® S100, a pH-dependent polymer with a high glass transition temperature. In Step II, a filament containing both sustained-release AAP from Step I and solubilized ibuprofen (IBF) was fabricated via HME at 110 °C using a mixture of hydroxy propyl cellulose (HPC-LF) and Eudragit® EPO, whose glass transition temperatures make them suitable for use in a 3D printer. A filament manufactured using DME was used to produce a cylindrical 3D-printed fixed-dose combination tablet with a diameter and height of 9 mm. To evaluate the release characteristics of the manufactured filament and 3D-printed tablet, dissolution tests were conducted for 10 h under simulated gastrointestinal tract conditions using the pH jump method with the United States Pharmacopeia apparatus II paddle method at 37 ± 0.5 °C and 50 rpm. Dissolution tests confirmed that both the sustained-release and solubilized forms of AAP and IBF within the filament and 3D-printed tablet exhibited distinct drug-release behaviors. The physicochemical properties of the filament and 3D-printed tablet were confirmed by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. HME transforms crystalline drugs into amorphous forms, demonstrating their physicochemical stability. Scanning electron microscopy and confocal laser scanning microscopy indicated the presence of sustained AAP granules within the filament, confirming that the drugs were independently separated within the filament and 3D-printed tablets. Finally, sustained-release AAP and solubilized IBF were independently incorporated into the filaments using DME technology. Therefore, a dual-release 3D-printed fixed-dose combination was prepared using the proposed filament.

10.
Nanomedicine ; 61: 102772, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960367

RESUMO

Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and ß-lapachone (ß-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.

11.
MAbs ; 16(1): 2373325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962811

RESUMO

T-cell engaging (TCE) bispecific antibodies are potent drugs that trigger the immune system to eliminate cancer cells, but administration can be accompanied by toxic side effects that limit dosing. TCEs function by binding to cell surface receptors on T cells, frequently CD3, with one arm of the bispecific antibody while the other arm binds to cell surface antigens on cancer cells. On-target, off-tumor toxicity can arise when the target antigen is also present on healthy cells. The toxicity of TCEs may be ameliorated through the use of pro-drug forms of the TCE, which are not fully functional until recruited to the tumor microenvironment. This can be accomplished by masking the anti-CD3 arm of the TCE with an autoinhibitory motif that is released by tumor-enriched proteases. Here, we solve the crystal structure of the antigen-binding fragment of a novel anti-CD3 antibody, E10, in complex with its epitope from CD3 and use this information to engineer a masked form of the antibody that can activate by the tumor-enriched protease matrix metalloproteinase 2 (MMP-2). We demonstrate with binding experiments and in vitro T-cell activation and killing assays that our designed prodrug TCE is capable of tumor-selective T-cell activity that is dependent upon MMP-2. Furthermore, we demonstrate that a similar masking strategy can be used to create a pro-drug form of the frequently used anti-CD3 antibody SP34. This study showcases an approach to developing immune-modulating therapeutics that prioritizes safety and has the potential to advance cancer immunotherapy treatment strategies.


Assuntos
Anticorpos Biespecíficos , Complexo CD3 , Imunoterapia , Pró-Fármacos , Linfócitos T , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/farmacologia , Humanos , Complexo CD3/imunologia , Imunoterapia/métodos , Linfócitos T/imunologia , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Engenharia de Proteínas/métodos , Metaloproteinase 2 da Matriz/imunologia
12.
Sci Rep ; 14(1): 15095, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956125

RESUMO

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.


Assuntos
Elastina , Nanogéis , Neoplasias de Próstata Resistentes à Castração , Masculino , Elastina/química , Humanos , Linhagem Celular Tumoral , Nanogéis/química , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Sistemas de Liberação de Medicamentos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Benzopiranos , Butiratos
13.
Adv Sci (Weinh) ; : e2403795, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995228

RESUMO

The constrained effectiveness of photodynamic therapy (PDT) has impeded its widespread use in clinical practice. Urgent efforts are needed to address the shortcomings faced in photodynamic therapy, such as photosensitizer toxicity, short half-life, and limited action range of reactive oxygen species (ROS). In this study, a biodegradable copolymer nanoamplifier is reported that contains ruthenium complex (Ru-complex) as photosensitizer (PS) and rhenium complex (Re-complex) as carbon monoxide (CO)-release molecule (CORM). The well-designed nanoamplifier brings PS and CORM into close spatial proximity, significantly promotes the utilization of light-stimulated reactive oxygen species (ROS), and cascaded amplifying CO release, thus enabling an enhanced synergistic effect of PDT and gas therapy for cancer treatment. Moreover, owing to its intrinsic photodegradable nature, the nanoamplifier exhibits good tumor accumulation and penetration ability, and excellent biocompatibility in vivo. These findings suggest that the biodegradable cascaded nanoamplifiers pave the way for a synergistic and clinically viable integration of photodynamic and gas therapy.

14.
Small ; : e2403835, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984921

RESUMO

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

15.
Mater Today Bio ; 27: 101126, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38994470

RESUMO

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

16.
ACS Nano ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018483

RESUMO

Neovascular age-related macular degeneration (AMD), a leading cause of blindness, requires frequent intravitreal injection of antivascular endothelial growth factor (anti-VEGF), which could generate a succession of complications with poor patient compliance. The current VEGF-targeting therapies often fail in half of patients due to the complex pathologic microenvironment of excessive reactive oxygen species (ROS) production, and increased levels of inflammation are accompanied by choroidal neovascularization (CNV). We herein reported multifunctional nanotherapeutics featuring superior antioxidant and anti-inflammation properties that aim to reverse the pathological condition, alongside its strong targeted antiangiogenesis to CNV and its ability to provide long-term sustained bioactive delivery via the minimally invasive subconjunctival injection, so as to achieve satisfactory wet AMD treatment effects. Concretely, the nanomedicine was designed by coencapsulation of astaxanthin (AST), a red pigmented carotenoid known for its antioxidative, anti-inflammatory and antiapoptotic properties, and axitinib (AXI), a small molecule tyrosine kinase inhibitor that selectively targets the vascular epidermal growth factor receptor for antiangiogenesis, into the Food and Drug Administration (FDA) approved poly(lactic-co-glycolic acid) (PLGA), which forms the nanodrug of PLGA@AST/AXI. Our results demonstrated that a single-dose subconjunctival administration of PLGA@AST/AXI showed a rational synergistic effect by targeting various prevailing risk factors associated with wet AMD, ensuring persistent drug release profiles, maintaining good ocular biocompatibility, and causing no obvious mechanical damage. Such attributes are vital and hold significant potential in treating ocular posterior segment diseases. Moreover, this nanotherapeutic strategy represents a versatile and broad-spectrum nanoplatform, offering a promising alternative for the complex pathological progression of other neovascular diseases.

17.
J Colloid Interface Sci ; 675: 1080-1090, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018635

RESUMO

Premature drug release in chemotherapy and hypoxic conditions in photodynamic therapy (PDT) are perplexing problems in tumor treatment. Thus, it is of great significance to develop the novel therapeutic system with controllable drug release and effective oxygen generation. Herein, a pH-responsive oxygen self-sufficient smart nanoplatform (named DHCCC), integrating hollow mesoporous silica nanoparticles (HMSNs), chitosan (CS), doxorubicin hydrochloride (DOX), chlorin e6 (Ce6) and catalase (CAT), is fabricated to enhance the tumor therapeutic efficacy efficiently through avoiding premature drug release and mitigating hypoxia of tumor microenvironment (TME). The drug DOX can be efficiently loaded into the HMSNs with large cavity and be controllable released because of the pH responsiveness of CS to the weak acidic TME, thereby elevating the chemotherapy efficacy. Meanwhile, CAT can catalyze the decomposition of endogenous hydrogen peroxide in situ generating oxygen to alleviate the hypoxia and enhance the PDT efficiency considerably. In vitro and in vivo results demonstrate that the combined chemo-photodynamic therapy based on the DHCCC nanoplatform exerts more effective antitumor efficacy than chemotherapy or PDT alone. The current study provides a promising inspiration to construct the pH-responsive oxygen self-sufficient smart nanomedicine with potentials to prevent premature drug leakage and overcome hypoxia for efficient tumor therapy.

18.
Carbohydr Res ; 543: 109207, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018698

RESUMO

Folic acid receptor-targeted drug delivery system is a promising candidate for tumor-targeted delivery because its elevated expression specifically on tumor cells enables the selective delivery of cytotoxic cargo to cancerous tissue, thereby minimizing toxic side effects and increasing the therapeutic index. Pyridine bisfolate-chitosan (PyBFA@CS NPs) and folate-chitosan nanocomposite (FA@CS NPs) were synthesized with suitable particle size (256.0 ± 15.0 and 161.0 ± 5.0 nm), high stability (ζ = -27.0 ± 0.1 and -30.0 ± 0.2 mV), respectively, and satisfactory biocompatibility to target cells expressing folate receptors and try to answer the question: Is the metal center always important for activity? Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding of human serum albumin (HSA) to PyBFA@CS NPs and FA@CS NPs has been investigated and compared with PyBFA. Strong affinity to HSA is shown by quenching and binding constants in the range of 105 and 104 M-1, respectively with PyBFA@CS NPs showing the strongest. The compounds-HSA kinetic stability, affinity, and association constants were investigated using a stopped-flow method. The findings showed that all formulations bind by a static quenching mechanism that consists of two reversible steps: rapid second-order binding and a more slowly first-order isomerization reaction. The overall coordination affinity of HSA to PyBFA@CS NPs (6.6 × 106 M-1), PyBFA (4.4 × 106 M-1), and FA@CS NPs (1.3 × 106 M-1) was measured and The relative reactivity is roughly (PyBFA@CS NPs)/(PyBFA)/(FA@CS NPs) = 5/3/1. Additionally, in vitro cytotoxicity revealed that, consistent with the binding constants and coordination affinity, active-targeting formulations greatly inhibited FR-positive MCF-7 cells in compared to FRs-negative A549 cells in the following trend: PyBFA@CS NPs > PyBFA > FA@CS NPs. Furthermore, in vitro drug release of PyBFA@CS NPs was found to be stable in PBS at pH 7.4, however, the in pH 5.4 and in pH 5.4 containing 10 mM glutathione (GSH) (mimicking the tumor microenvironment) reached 43 % and 73 %, respectively indicating that the PyBFA@CS NPs system is sensitive to GSH. Folate-modified nanoparticles, PyBFA@CS NPs, are a promising therapeutic for MCF-7 therapy because they not only showed a greater affinity for HSA, but also showed higher cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way, as well as effective antibacterial activity that avoids the usage of extra antibiotics.‬‬‬‬‬‬‬‬‬‬‬‬ ‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

19.
J Environ Manage ; 366: 121871, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39018844

RESUMO

To assess the application potential of sewage sludge biochar produced by industrial-scale pyrolysis (ISB), the release characteristics of nutrients (NH4+, PO43-, K, Ca, Mg and Fe) and heavy metals (Mn, Cu, Zn, Pb, Ni and Cr) were investigated. Their release amounts increased with decreasing initial pH and increasing solid-liquid ratios (RS-L) and temperature. The release types of NH4+, K, Mg, and Mn were diffusion/dissolution, while those of Cu, Zn, Pb, Ni, and Cr were diffusion/resorption. The release types of PO43- and Ca varied with initial pH and RS-L, respectively. The chemical actions played dominant roles in their release, while particle surface diffusion and liquid film diffusion determined the rates of diffusion and resorption phases, respectively. The release of NH4+, PO43-, K, Ca, Mg, Mn and Zn was a non-interfering, spontaneous (except PO43-), endothermic, and elevated randomness process. The release efficiency of NH4+, PO43- and K met the Chinese standard for slow-release fertilizers, while the total risk of ISB was low. The eutrophication and potential ecological risks of ISB were acceptable when the dose was less than 3 g L-1 and the initial pH was no lower than 3. In conclusion, ISB had potential as a slow-release fertilizer and adsorbent.

20.
J Diabetes Complications ; 38(8): 108809, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018898

RESUMO

AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...