Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
Nutr Cancer ; : 1-24, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847479

RESUMEN

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/ß-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

2.
Biopharm Drug Dispos ; 45(2): 71-82, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38400763

RESUMEN

This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P-gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P-gp, but the observations suggest that P-gp is significant in reducing vildagliptin absorption. Verapamil co-perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co-administration showed a non-significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site-dependent and may be related to the intestinal P-glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug-drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P-glycoprotein level.


Asunto(s)
Metformina , Animales , Humanos , Conejos , Vildagliptina/farmacología , Metformina/farmacología , Verapamilo/farmacología , Absorción Intestinal , Intestinos , Subfamilia B de Transportador de Casetes de Unión a ATP
3.
Chem Biodivers ; 21(2): e202301470, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38161147

RESUMEN

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Liposomas , Ácido Hialurónico , Doxorrubicina/farmacología , Células MCF-7
4.
J Liposome Res ; 34(1): 178-202, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37378553

RESUMEN

Liposomes are spherical lipidic nanocarriers composed of natural or synthetic phospholipids with a hydrophobic bilayer and aqueous core, which are arranged into a polar head and a long hydrophobic tail, forming an amphipathic nano/micro-particle. Despite numerous liposomal applications, their use encounters many challenges related to the physicochemical properties strongly affected by their constituents, colloidal stability, and interactions with the biological environment. This review aims to provide a perspective and a clear idea about the main factors that regulate the liposomes' colloidal and bilayer stability, emphasising the roles of cholesterol and its possible alternatives. Moreover, this review will analyse strategies that offer possible approaches to provide more stable in vitro and in vivo liposomes with enhanced drug release and encapsulation efficiencies.


Asunto(s)
Liposomas , Fosfolípidos , Liposomas/química , Fosfolípidos/química , Colesterol/química , Estabilidad de Medicamentos
5.
Environ Res ; 238(Pt 1): 117088, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37683781

RESUMEN

Water treatment is crucial in solving the rising people's appetite for water and global water shortages. Carbon nanotubes (CNTs) have considerable promise for water treatment because of their adjustable and distinctive arbitrary, physical, as well as chemical characteristics. This illustrates the benefits and risks of integrating CNT into the traditional water treatment resource. Due to their outstanding adsorbent ability and chemical and mechanical properties, CNTs have gained global consideration in environmental applications. The desalination and extraction capability of CNT were improved due to chemical or physical modifications in pure CNTs by various functional groups. The CNT-based composites have many benefits, such as antifouling performance, high selectivity, and increased water permeability. Nevertheless, their full-scale implementations are still constrained by their high costs. Functionalized CNTs and their promising nanocomposites to eliminate contaminants are advised for marketing and extensive water/wastewater treatment.


Asunto(s)
Nanotubos de Carbono , Purificación del Agua , Humanos , Nanotubos de Carbono/química
6.
Environ Res ; 238(Pt 2): 116909, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37673119

RESUMEN

Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.


Asunto(s)
Oryza , Contaminantes Químicos del Agua , Humanos , Oryza/química , Agua , Colorantes/química , Adsorción , Cinética , Contaminantes Químicos del Agua/análisis , Concentración de Iones de Hidrógeno
7.
Drug Dev Ind Pharm ; 49(6): 393-404, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37272678

RESUMEN

OBJECTIVE: This article critically reviews recent research on the use of trimetallic nanomaterials for the fabrication of non-enzymatic glucose sensors (NEGS), also known as fourth-generation glucose sensors (FGGS). SIGNIFICANCE: Diabetes is a prevalent chronic disease worldwide, and glucose monitoring is crucial for its management. However, conventional enzymatic glucose sensors suffer from several technological drawbacks, and there is a need to develop new-generation glucose sensors that can overcome these limitations. NEGS, particularly those composed of trimetallic nanocomposites, have demonstrated promising results in terms of improved shelf life, higher sensitivity, and simplicity of operation during glucose measurement. METHODS: In this review, we discuss the different trimetallic nanomaterials developed and used by researchers in recent years for glucose detection, including their mechanisms of action. We also provide a brief discussion of the advantages and disadvantages of FGGS-based trimetallic nanomaterials, as well as the industrial challenges in this area of research. RESULTS: Trimetallic nanomaterials for FGGS have shown excellent reproducibility and high stability, making them suitable for continuous glucose monitoring. The different types of trimetallic nanomaterials have varying sensing properties, and their performance can be tuned by controlling their synthesis parameters. CONCLUSION: Trimetallic nanomaterials are a promising avenue for the development of FGGS, recent research has demonstrated their potential for glucose monitoring. However, there are still some challenges that need to be addressed before their widespread adoption, such as their long-term stability and cost-effectiveness. Further research in this area is needed to overcome these challenges and to develop commercially viable FGGS for diabetes management.


Asunto(s)
Técnicas Biosensibles , Diabetes Mellitus , Nanocompuestos , Humanos , Glucemia , Automonitorización de la Glucosa Sanguínea , Reproducibilidad de los Resultados , Técnicas Biosensibles/métodos , Diabetes Mellitus/diagnóstico , Glucosa
8.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36834476

RESUMEN

Ran is a member of the Ras superfamily of proteins, which primarily regulates nucleocytoplasmic trafficking and mediates mitosis by regulating spindle formation and nuclear envelope (NE) reassembly. Therefore, Ran is an integral cell fate determinant. It has been demonstrated that aberrant Ran expression in cancer is a result of upstream dysregulation of the expression of various factors, such as osteopontin (OPN), and aberrant activation of various signaling pathways, including the extracellular-regulated kinase/mitogen-activated protein kinase (ERK/MEK) and phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) pathways. In vitro, Ran overexpression has severe effects on the cell phenotype, altering proliferation, adhesion, colony density, and invasion. Therefore, Ran overexpression has been identified in numerous types of cancer and has been shown to correlate with tumor grade and the degree of metastasis present in various cancers. The increased malignancy and invasiveness have been attributed to multiple mechanisms. Increased dependence on Ran for spindle formation and mitosis is a consequence of the upregulation of these pathways and the ensuing overexpression of Ran, which increases cellular dependence on Ran for survival. This increases the sensitivity of cells to changes in Ran concentration, with ablation being associated with aneuploidy, cell cycle arrest, and ultimately, cell death. It has also been demonstrated that Ran dysregulation influences nucleocytoplasmic transport, leading to transcription factor misallocation. Consequently, patients with tumors that overexpress Ran have been shown to have a higher malignancy rate and a shorter survival time compared to their counterparts.


Asunto(s)
GTP Fosfohidrolasas , Neoplasias , Humanos , GTP Fosfohidrolasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína de Unión al GTP ran/genética , Neoplasias/patología , Fenotipo
9.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36768330

RESUMEN

Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.


Asunto(s)
Nanopartículas , Nanoestructuras , Nanoestructuras/toxicidad , Nanopartículas/química , Sistema Inmunológico , Polímeros/química , Inmunización
10.
Pharm Res ; 36(2): 26, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30560466

RESUMEN

BACKGROUND: Overexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays. METHODS: Biodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down. RESULTS: shRNA-loaded nanoparticles were successfully fabricated and delivered to MDA-MB231 cells in culture, where they effectively released their payload, causing a decrease in both cell invasion and cell migration by knocking down RAN gene expression. CONCLUSION: Results indicate the anti-RAN shRNA-loaded nanoparticles deliver and release biological payload to MDA-MB231 cells in culture. This works paves the way for further investigations into the possible use of anti-RAN shRNA-loaded NP formulations for the treatment of breast cancer in vivo.


Asunto(s)
Portadores de Fármacos/química , Nanopartículas/química , Poliglactina 910/química , ARN Interferente Pequeño/genética , Neoplasias de la Mama , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Liberación de Fármacos , Femenino , Técnicas de Silenciamiento del Gen , Técnicas de Transferencia de Gen , Humanos , Tamaño de la Partícula , ARN Interferente Pequeño/farmacología , Propiedades de Superficie
11.
Br J Haematol ; 168(3): 429-42, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25283956

RESUMEN

Recombinant human erythropoietin (rHuEPO) is an effective treatment for anaemia but concerns that it causes disease progression in cancer patients by activation of EPO receptors (EPOR) in tumour tissue have been controversial and have restricted its clinical use. Initial clinical studies were flawed because they used polyclonal antibodies, later shown to lack specificity for EPOR. Moreover, multiple isoforms of EPOR caused by differential splicing have been reported in cancer cell lines at the mRNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The EpoCan consortium seeks to promote improved pathological testing of EPOR, leading to safer clinical use of rHuEPO, by producing well characterized EPOR antibodies. Using novel genetic and traditional peptide immunization protocols, we have produced mouse and rat monoclonal antibodies, and show that several of these specifically recognize EPOR by Western blot, immunoprecipitation, immunofluorescence, flow cytometry and immunohistochemistry in cell lines and clinical material. Widespread availability of these antibodies should enable the research community to gain a better understanding of the role of EPOR in cancer, and eventually to distinguish patients who can be treated safely by rHuEPO from those at increased risk from treatment.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Proteínas de Neoplasias/inmunología , Receptores de Eritropoyetina/inmunología , Secuencia de Aminoácidos , Animales , Técnicas de Química Sintética/métodos , Citometría de Flujo/métodos , Técnica del Anticuerpo Fluorescente , Silenciador del Gen , Humanos , Inmunoprecipitación , Ratones , Datos de Secuencia Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ratas , Receptores de Eritropoyetina/genética , Receptores de Eritropoyetina/metabolismo , Medición de Riesgo/métodos , Terminología como Asunto , Células Tumorales Cultivadas/metabolismo
12.
Adv Exp Med Biol ; 773: 323-51, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24563355

RESUMEN

Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of macromolecules across the nuclear envelope. It binds to chromatin early during nuclear formation and has important roles during the eukaryotic cell cycle, where it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle checkpoint control. Like other GTPases, Ran relies on the cycling between GTP-bound and GDP-bound conformations to interact with effector proteins and regulate these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear envelope through nuclear pores. It is concentrated in the nucleus by an active import mechanism where it generates a high concentration of RanGTP by nucleotide exchange. It controls the assembly and disassembly of a range of complexes that are formed between Ran-binding proteins and cellular cargo to maintain rapid nuclear transport. Ran also has been identified as an essential protein in nuclear envelope formation in eukaryotes. This mechanism is dependent on importin-ß, which regulates the assembly of further complexes important in this process, such as Nup107-Nup160. A strong body of evidence is emerging implicating Ran as a key protein in the metastatic progression of cancer. Ran is overexpressed in a range of tumors, such as breast and renal, and these perturbed levels are associated with local invasion, metastasis and reduced patient survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are addicted to Ran expression, which yields exciting future therapeutic opportunities.


Asunto(s)
Metástasis de la Neoplasia , Neoplasias/patología , Membrana Nuclear/fisiología , Proteína de Unión al GTP ran/metabolismo , Transporte Activo de Núcleo Celular , Ciclo Celular , Humanos , Conformación Proteica , Huso Acromático , Proteína de Unión al GTP ran/química , Proteína de Unión al GTP ran/fisiología
13.
Crit Rev Oncol Hematol ; : 104438, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38977145

RESUMEN

Cancer metabolism is now a key area for therapeutic intervention, targeting unique metabolic reprogramming crucial for tumor growth and survival. This article reviews the therapeutic potential of addressing metabolic vulnerabilities through glycolysis and glutaminase inhibitors, which disrupt cancer cell metabolism. Challenges such as tumor heterogeneity and adaptive resistance are discussed, with strategies including personalized medicine and predictive biomarkers to enhance treatment efficacy. Additionally, integrating diet and lifestyle changes with metabolic targeting underscores a holistic approach to improving therapy outcomes. The article also examines the benefits of incorporating these strategies into standard care, highlighting the potential for more tailored, safer treatments. In conclusion, exploiting metabolic vulnerabilities promises a new era in oncology, positioning metabolic targeting at the forefront of personalized cancer therapy and transforming patient care.

14.
Expert Opin Drug Deliv ; 21(2): 309-324, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38284386

RESUMEN

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques. EXPERT OPINION: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Liposomas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Microambiente Tumoral
15.
Gene ; 905: 148174, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38242374

RESUMEN

The intersection of mathematical modeling, nanotechnology, and epidemiology marks a paradigm shift in our battle against infectious diseases, aligning with the focus of the journal on the regulation, expression, function, and evolution of genes in diverse biological contexts. This exploration navigates the intricate dance of viral transmission dynamics, highlighting mathematical models as dual tools of insight and precision instruments, a theme relevant to the diverse sections of Gene. In the context of virology, ethical considerations loom large, necessitating robust frameworks to protect individual rights, an aspect essential in infectious disease research. Global collaboration emerges as a critical pillar in our response to emerging infectious diseases, fortified by the predictive prowess of mathematical models enriched by nanotechnology. The synergy of interdisciplinary collaboration, training the next generation to bridge mathematical rigor, biology, and epidemiology, promises accelerated discoveries and robust models that account for real-world complexities, fostering innovation and exploration in the field. In this intricate review, mathematical modeling in viral transmission dynamics and epidemiology serves as a guiding beacon, illuminating the path toward precision interventions, global preparedness, and the collective endeavor to safeguard human health, resonating with the aim of advancing knowledge in gene regulation and expression.


Asunto(s)
Enfermedades Transmisibles , Humanos , Enfermedades Transmisibles/epidemiología , Modelos Teóricos , Matemática
16.
Nanomedicine (Lond) ; 19(12): 1087-1101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38661720

RESUMEN

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.


[Box: see text].


Asunto(s)
Neoplasias de la Mama , Neoplasias Pulmonares , Mebendazol , Mebendazol/farmacología , Mebendazol/uso terapéutico , Humanos , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Línea Celular Tumoral , Ratones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Portadores de Fármacos/química , Lípidos/química , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Desnudos
17.
Int J Pharm ; 650: 123678, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38065344

RESUMEN

The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.


Asunto(s)
Antiinfecciosos , Infecciones por VIH , Nanotubos de Carbono , Humanos , Nanotubos de Carbono/química , Inhibidores de Proteasas , Hemólisis , Sistemas de Liberación de Medicamentos , Inhibidores Enzimáticos , Antivirales
18.
Cell Signal ; 115: 111013, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38113978

RESUMEN

The gut microbiota present in the human digestive system is incredibly varied and is home to trillions of microorganisms. The gut microbiome is shaped at birth, while numerous genetic, dietary, and environmental variables primarily influence the microbiome composition. The importance of gut microbiota on host health is becoming more widely acknowledged. Digestion, intestinal permeability, and immunological and metabolism responses can all be affected by changes in the composition and function of the gut microbiota. There is mounting evidence that the microbial population's complex traits are important biomarkers and indicators of patient outcomes in cancer and its therapies. Numerous studies have demonstrated that changed commensal gut microorganisms contribute to the development and spread of cancer through various routes. Despite the ongoing controversy surrounding the gut microbiome and gastrointestinal cancer, accumulating evidence points to a potentially far more intricate connection than a simple cause-and-effect relationship. SIMPLE SUMMARY: Due to their high frequency and fatality rate, gastrointestinal cancers are regarded as a severe public health issue with complex medical and economic burdens. The gut microbiota may directly or indirectly interact with existing therapies like immunotherapy and chemotherapy, affecting how well a treatment works. The gut microbiome influences the immune response's activity, function, and development. Generally, certain gut bacteria impact the antitumor actions during cancer by creating particular metabolites or triggering T-cell responses. Yet, certain bacterial species have been found to promote cellular proliferation and metastasis in cancer, and comprehending these interactions in the context of cancer may help identify possible treatment targets. Notwithstanding the improvements in the field, additional research is still required to comprehend the underlying processes, examine the effects on existing therapies, and pinpoint certain bacteria and immune cells that can cause this interaction.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias Gastrointestinales , Microbiota , Recién Nacido , Humanos , Bacterias/genética
19.
Bioanalysis ; 16(9): 369-384, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38497721

RESUMEN

This study was conducted to compare dissolution profiles of four Jordanian registered sildenafil (SDF) products to the originator. Dissolution samples were analyzed utilizing a validated and stability-indicating HPLC method in human plasma. Validation was performed for specificity, linearity, limit of detection, lower limit of quantification, precision, trueness and stability. SDF was extracted from plasma samples using liquid-liquid extraction. The analysis was performed utilizing isocratic elution on C18 column with 1.0 ml/min flow rate. The regression value was ∼0.999 over 3 days with drug recovery between 86.6 to 89.8%with 10 ng/ml lower limit of quantitation. This method displayed a good selectivity of SDF with improved stability under various conditions. The method was used for SDF quantification in dissolution medium. Similarity factors for local products varied according to the used mediums, but all SDF local products passed the dissolution in vitro test since all of them showed a released of >85% after 60 min at the dissolution mediums.


[Box: see text].


Asunto(s)
Citrato de Sildenafil , Citrato de Sildenafil/sangre , Citrato de Sildenafil/química , Citrato de Sildenafil/análisis , Cromatografía Líquida de Alta Presión/métodos , Humanos , Medicamentos Genéricos/química , Medicamentos Genéricos/análisis , Solubilidad , Jordania , Estabilidad de Medicamentos , Límite de Detección
20.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38931404

RESUMEN

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with ß-cyclodextrin (ßCD) and hydroxy propyl ß-cyclodextrin (HPßCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with ßCD and HPßCD. This study identified the most soluble complex (ALB-HPßCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPßCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPßCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda