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1.
Curr Med Chem ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38445701

RESUMO

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

2.
Curr Protein Pept Sci ; 25(1): 4-11, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37183462

RESUMO

The human genetic structure undergoes continuous wear and tear process due to the mere presence of extrinsic as well as intrinsic factors. In normal physiological cells, DNA damage initiates various checkpoints that may activate the repair system or induce apoptosis that helps maintain cellular integrity. While in cancerous cells, due to alterations in signaling pathways and defective checkpoints, there exists a marked deviation of error-free DNA repairing/synthesis. Currently, cancer therapy targeting the DNA damage response shows significant therapeutic potential by tailoring the therapy from non-specific to tumor-specific activity. Recently, numerous drugs that target the DNA replicating enzymes have been approved or some are under clinical trial. Drugs like PARP and PARG inhibitors showed sweeping effects against cancer cells. This review highlights the mechanistic study of different drug categories that target DNA replication and thus depicts the futuristic approach of targeted therapy.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Dano ao DNA , Reparo do DNA , Replicação do DNA , DNA
3.
Cureus ; 15(9): e46186, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37908964

RESUMO

Background Anterior cruciate ligament (ACL) injury is most common among athletes compared to the general population. ACL reconstruction is a clinical standard for restoring joint mechanical stability and enabling sports return. The purpose of the study is to evaluate the safety and functional outcomes after arthroscopic ACL reconstruction using the Sironix titanium button and the polyetheretherketone (PEEK) button. Methods A total of 31 subjects who have undergone arthroscopic ACL reconstruction using the Sironix titanium button and PEEK button between August 2022 and January 2023 were included in the study. Demographic data, surgery details, and other baseline characteristics of the subjects were collected from the hospital records. The primary objective of the study was to assess the functional outcome using the International Knee Documentation Committee (IKDC) questionnaire. The secondary objectives were to determine the pre- and post-surgery activity levels using the Tegner Activity Score (TAS) and Lysholm score. Quality of life evaluation was done by using the Quality of Life (QoL) subscale from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE). Device-related adverse effect information was recorded. Results The mean (SD) of the total IKDC score of 31 subjects at baseline and post-surgery was 51.4 (2.84) and 91.8 (2.59) out of 100, respectively. The mean (SD) of TAS pre-injury and post-surgery was 5.3 (1.47) and 5.4 (1.38) out of 10, respectively. The total mean (SD) value of the total Lysholm Score at baseline and post-surgery was 53.9 (3.72) and 91.4 (3.61) out of 100, respectively. The mean (SD) value of the quality of life subscale of the KOOS score was 91.2 (3.91) out of 100. The total mean (SD) value of the SANE score that had affected joint/region of interest today was 97.4 (1.78), while for the opposite side today, it was 99.5 (0.85) out of 100. There were no adverse device effects reported in this study. Conclusion Based on the score assessment, it was observed that the performance of Sironix knee implant devices, Proloop-Titanium adjustable loop button, T-Button A® Closed PEEK button, and Surestitch® All Inside Meniscal Repair Implant (Healthium Medtech Limited, Bengaluru, Karnataka, India) was effective and safe with no adverse effects. Therefore, Sironix knee implants are considered safe and effective in ACL reconstruction and meniscus repair surgery.

4.
Curr Med Chem ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37828674

RESUMO

Nanomedicine's application of nanotechnology in medicine holds tremendous potential for diagnosing and treating life-threatening diseases such as cancer. Unlike conventional therapies, nanomedicine offers a promising strategy to enhance clinical outcomes while minimizing severe side effects. The principle of drug targeting enables specific delivery of therapeutic agents to their intended sites, making it a more precise and effective therapy. Combination strategies, such as the co-delivery of chemotherapeutic drugs with nucleic acids or receptor-specific molecules, are being employed to enhance therapeutic outcomes. Nanocarriers and drug delivery systems designed using these approaches offer resourceful co-delivery of therapeutic agents for anticancer therapy. Targeted drug delivery via nanotechnology-based techniques has become an urgent need and has shown significant improvements in therapeutic implications, pharmacokinetics, specificity, reduced toxicity, and biocompatibility. This review discusses the extrapolation of nanomaterials for developing innovative and novel drug delivery systems for effective anticancer therapy. Additionally, we explore the role of nanotechnology-based concepts in drug delivery research.

5.
AAPS PharmSciTech ; 24(6): 170, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566146

RESUMO

Since the ground-breaking discovery of RNA interference (RNAi), scientists have made significant progress in the field of small interfering RNA (siRNA) treatments. Due to severe barriers to the therapeutic application of siRNA, nanoparticle technologies for siRNA delivery have been designed. For pathological circumstances such as viral infection, toxic RNA abnormalities, malignancies, and hereditary diseases, siRNAs are potential therapeutic agents. However, systemic administration of siRNAs in vivo remains a substantial issue due to a lack of "drug-likeness" (siRNA are relatively larger than drugs and have low hydrophobicity), physiological obstacles, and possible toxicities. This write-up covers important accomplishment in the field of clinical trials and patents specially based of siRNAs using targeting viruses. Furthermore, it offers deep insight of nanoparticle applied for siRNA delivery and strategies to improve the effectiveness of antivirals.


Assuntos
Fármacos Dermatológicos , Nanopartículas , Neoplasias , Humanos , RNA Interferente Pequeno/uso terapêutico , Antivirais/uso terapêutico , Interferência de RNA , Neoplasias/tratamento farmacológico
6.
Curr Pharm Biotechnol ; 24(14): 1727-1739, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36861800

RESUMO

COVID-19, an extremely transmissible and pathogenic viral disease, triggered a global pandemic that claimed lives worldwide. To date, there is no clear and fully effective treatment for COVID-19 disease. Nevertheless, the urgency to discover treatments that can turn the tide has led to the development of a variety of preclinical drugs that are potential candidates for probative results. Although most of these supplementary drugs are constantly being tested in clinical trials against COVID-19, recognized organizations have aimed to outline the prospects in which their use could be considered. A narrative assessment of current articles on COVID-19 disease and its therapeutic regulation was performed. This review outlines the use of various potential treatments against SARS-CoV-2, categorized as fusion inhibitors, protease inhibitors, and RNA-dependent RNA polymerase inhibitors, which include antiviral drugs such as Umifenovir, Baricitinib, Camostatmesylate, Nafamostatmesylate, Kaletra, Paxlovide, Darunavir, Atazanavir, Remdesivir, Molnupiravir, Favipiravir, and Ribavirin. To understand the virology of SARS-CoV-2, potential therapeutic approaches for the treatment of COVID-19 disease, synthetic methods of potent drug candidates, and their mechanisms of action have been addressed in this review. It intends to help readers approach the accessible statistics on the helpful treatment strategies for COVID-19 disease and to serve as a valuable resource for future research in this area.


Assuntos
Antivirais , COVID-19 , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , SARS-CoV-2 , Darunavir/farmacologia , Inibidores de Proteases/farmacologia
7.
Curr Pharm Biotechnol ; 24(11): 1420-1429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36578251

RESUMO

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.


Assuntos
Diabetes Mellitus , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos , Lipossomos , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Polímeros/uso terapêutico , Portadores de Fármacos
8.
ChemSusChem ; 16(1): e202201846, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36354122

RESUMO

5-Hydroxymethylfurfural (5-HMF) represents a well-known class of lignocellulosic biomass-derived platform molecules. With the presence of many reactive functional groups in the structure, this versatile building block could be valorized into many value-added products. Among well-established catalytic transformations in biorefinery, the reductive amination is of particular interest to provide valuable N-containing compounds. Specifically, the reductive amination of 5-HMF with ammonia (NH3 ) and molecular hydrogen (H2 ) offers a straightforward and sustainable access to primary furanic amines [i. e., 5-hydroxymethyl-2-furfuryl amine (HMFA) and 2,5-bis(aminomethyl)furan (BAMF)], which display far-reaching utilities in pharmaceutical, chemical, and polymer industries. In the presence of heterogeneous catalysts contanining monometals (Ni, Co, Ru, Pd, Pt, and Rh) or bimetals (Ni-Cu and Ni-Mn), this elegant pathway enables a high-yielding and chemoselective production of HMFA/BAMF compared to other synthetic routes. This Review aims to present an up-to-date highlight on the supported metal-catalyzed reductive amination of 5-HMF with elaborate studies on the role of metal, solid support, and reaction parameters. Besides, the recyclability/adaptability of catalysts as well as the reaction mechanism are also provided to give valuable insights into this potential 5-HMF valorization strategy.


Assuntos
Aminas , Furaldeído , Aminação , Aminas/química , Furaldeído/química , Catálise
9.
Narra J ; 3(2): e147, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38454981

RESUMO

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

10.
Turk J Pharm Sci ; 19(4): 476-487, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36047602

RESUMO

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of recently developed approaches for GRDDS.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35578839

RESUMO

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Biotechnology.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

12.
Sci Rep ; 12(1): 4095, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260780

RESUMO

Asphaltenes from bitumen are abundant resource to be transformed into carbon as promising supercapacitor electrodes, while there is a lack of understanding the impact from different fractions of bitumen and asphaltenes, as well as the presence of transition metals. Here, nanoporous carbon was synthesized from bitumen, hexane-insoluble asphaltenes and N,N-dimethylformamide (DMF)-fractionated asphaltenes by using Mg(OH)2 nanoplates as the template with in-situ KOH activation, and used as an supercapacitor electrode material. All of the carbon exhibited large surface area (1500-2200 m2 g-1) with a distribution of micro and mesopores except for that derived from the DMF-soluble asphaltenes. The pyrolysis of asphaltenes resulted in the formation of nickel oxide/carbon composite (NiO/C), which demonstrated high capacitance of 380 F g-1 at 1 A g-1 discharge current resulting from the pseudocapacitance of NiO and the electrochemical double layer capacitance of the carbon. The NiO/C composite obtained from the DMF-insoluble portion had low NiO content which led to lower capacitance. Meanwhile, the specific capacitance of NiO/C composite from the DMF-soluble part was lower than the unfractionated asphaltene due to the higher NiO content resulting in lower conductivity. Therefore asphaltenes derived from nickel-rich crude bitumen is suitable for the synthesis of nanoporous NiO/C composite material with high capacitance.

13.
ChemSusChem ; 15(13): e202200178, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35286783

RESUMO

5-Hydroxymethylfurfural (5-HMF), one of the most important platform molecules in biorefinery, can be directly obtained from a vast diversity of biomass materials. Owing to the reactive functional groups (-CHO and -CH2 OH) in the structure, this versatile building block undertakes several transformations to provide a wealth of high value-added products. Among numerous well-established paradigms, the catalytic hydrogenation of 5-HMF towards 2,5-bis(hydroxymethyl)tetrahydrofuran (BHMTHF) is of great interest because this downstream diol can be exploited in a wide range of industrial applications. Not surprisingly, incessant endeavors from both academia and industry to upgrade this catalytic process have been established over the years. The main aim of this Review was to provide a comprehensive overview on the development of heterogeneous metal catalysts for the 5-HMF-to-BHMTHF transformation. Herein, the rational design and utility of hydrogenating catalysts were elaborated in many aspects including metal types (Ni, Co, Pd, Ru, Pt, and bimetals), solid supports, preparation method, recyclability, operating conditions, and reaction regime (batch and continuous flow). In addition, the assessment of cooperative catalysts to convert carbohydrates into BHMTHF under one-pot cascade, tentative mechanism, as well as prospects and challenges for the chemo-selective hydrogenation of 5-HMF were also highlighted.


Assuntos
Furaldeído , Furanos , Biomassa , Catálise , Furaldeído/análogos & derivados , Furaldeído/química , Furanos/química , Metais/química
14.
Small ; 17(49): e2103521, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34655150

RESUMO

The ultrastretchable (over 12 400%) hydrogel with long-lasting adhesion, strong antibacterial activity, and robust spinnability is developed based on the oxidative decarboxylation and quinone-catechol reversible redox reaction induced by Ag-lignin nanoparticles in a precursor solution containing citric acid (CA), acrylic acid (AA), and poly (acrylamide-co-acrylic acid) (P(AAm-co-AA)). With massive reversible interactions including hydrogen bonds and electrostatic forces, such hydrogel exhibits promising injectability and is facilely spun via manual drawing, draw-spinning, and electrospinning for manufacturing strong hydrogel micro/nanofibers. The resulting fibers exhibit excellent mechanical properties, including tensile stress of 422.0 MPa, strain of 86.5%, Young's modulus of 8.7 GPa, and toughness of 281.6 MJ m-3 . The hydrogel microfibers obtained from a house-built spinner are scaled-up fabricated while retaining promising mechanical properties, as evidenced by lifting a load (317.2 g) using the spun fibers of ≈33 000 times lighter weight (9.5 mg), indicating their great potentials in the applications such as net and safety cord which require robust mechanical properties. Moreover, assisted by a commercial electrospinning machine, nanosized hydrogel fibers are facilely spun on personal protective equipment such as a mask to offer an antiseptic coating with near 100% killing efficiency against airborne bacteria aerosols, demonstrating the capability of spun hydrogel fibers on disinfection-related applications.


Assuntos
Nanofibras , Adesivos , Antibacterianos/farmacologia , Módulo de Elasticidade , Hidrogéis
15.
Water Res ; 200: 117202, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015576

RESUMO

Warm lime softening is commonly used to reduce hardness, silica, and a small fraction of organic matter from steam-assisted gravity drainage (SAGD) produced water through the addition of lime, soda ash, MgO, coagulant and flocculant. We report a systematic study on the impact of solution chemistry on the epichlorohydrin-dimethylamine coagulant demand for the treatment of synthetic SAGD produced water. Concentrations of magnesium, calcium, sodium bicarbonate, clay (mimicking suspended solids), sodium metasilicate (representing silica), and humic acid (mimicking dissolved organic matter) were varied to study their impact on coagulant demand. The impact of the concentration of lime, soda ash, and MgO on coagulant demand was also studied. Within the studied concentration range, the coagulant dose increased linearly with increasing concentration of humic acid (Ycoagulant = 29 + 0.703XHA) and silica (Ycoagulant = 52 + 0.537Xsilica), and increased slightly with increasing concentration of lime and soda ash, but remained almost unchanged with increasing concentration of dissolved hardness, clay, or MgO. The observations were correlated to the understanding of the electrokinetic properties of CaCO3 and Mg(OH)2 particles in lime softening. The findings provide insights for evaluating onsite coagulant dose and optimizing the process.


Assuntos
Abrandamento da Água , Água , Compostos de Cálcio , Óxidos , Polímeros , Vapor
16.
Int J Biol Macromol ; 179: 500-506, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33711369

RESUMO

The main aim of the present study is to synthesize a hitherto unreported polymer of chitosan (CS) and 2,5-furandicarboxylic acid (FDCA) derived from renewable biomass resources. For this purpose, CS was chosen which had -NH2 groups as abundant active sites. Synthesis of 2,5-furandicarboxylic acid-enriched-chitosan polymer (CS-FDCA) was carried out by reaction involving EDC-NHS coupling reagents. The structure of CS-FDCA polymer was confirmed by various characterization techniques such as Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), X-ray powder diffraction (XRD), high resolution-field emission scanning electron microscope (HR-FESEM), and thermogravimetric analysis (TGA). Moreover, CS and CS-FDCA were scrutinized to examine their efficacies towards ameliorate inflammation via detection of lipopolysaccharide (LPS) induced nitric oxide (NO) production. As compared to CS, CS-FDCA with low concentration (1.0 µM) exhibited the better efficacy to reduce the NO production. Furthermore, CS-FDCA polymer showed high as 12.6% of Cu2+ ion uptake while CS showed 9.2% of Cu2+ ion uptake. Overall, it can be inferred that CS-FDCA polymer is expected to be used for biomedical application and for the removal of metal contaminants from industrial wastewater.


Assuntos
Anti-Inflamatórios/síntese química , Quitosana/química , Ácidos Dicarboxílicos/química , Furanos/química , Metais/química , Purificação da Água
17.
Eur J Pharm Biopharm ; 161: 100-119, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33639254

RESUMO

Potential research outcomes on nanotechnology-based novel drug delivery systems since the past few decades attracted the attention of the researchers to overcome the limitations of conventional deliveries. Apart from possessing enhanced solubility of poorly water-soluble drugs, the targeting potential of the carriers facilitates longer circulation and site-specific delivery of the entrapped therapeutics. The practice of these delivery systems, therefore, helps in maximizing bioavailability, improving pharmacokinetics profile, pharmacodynamics activity and biodistribution of the entrapped drug(s). In addition to focusing on the positive side, evaluation of nanoparticulate systems for toxicity is a crucial parameter for its biomedical applications. Due to the size of nanoparticles, they easily traverse through biological barriers and may be accumulated in the body, where the ingredients incorporated in the formulation development might accumulate and/or produce toxic manifestation, leading to cause severe health hazards. Therefore, the toxic profile of these delivery systems needs to be evaluated at the molecular, cellular, tissue and organ level. This review offers a comprehensive presentation of toxicity aspects of the constituents of nanoparticular based drug delivery systems, which would be beneficial for future researchers to develop nanoparticulate delivery vehicles for the improvement of delivery approaches in a safer way.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Humanos , Nanopartículas/toxicidade , Nanotecnologia , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade , Distribuição Tecidual
18.
J Med Econ ; 24(1): 131-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33397178

RESUMO

AIMS: To estimate the budget impact of adding capmatinib, the first FDA approved MET inhibitor, to a US commercial or Medicare health plan for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation that leads to MET exon 14 (METex14) skipping. METHODS: Target population size was estimated using published epidemiology data. Clinical data were obtained from the GEOMETRY mono-1 capmatinib trial and published trials. Treatments in the market mix included crizotinib, pembrolizumab, ramucirumab, and chemotherapy. Uptake of capmatinib and testing rates were based on market research. All costs (drug acquisition and administration, pre-progression, progression, terminal care, adverse event, and testing) were estimated based on public sources (2020 USD). RESULTS: The number of patients eligible for capmatinib in the first three years was estimated to be 2-3 in a hypothetical 1 million member commercial plan and 34-44 in a hypothetical 1 million member Medicare plan each year. The estimated total budget impact ranged from $9,695 to $67,725 for a commercial plan and $141,350 to $985,695 for Medicare. With capmatinib included, a marginal per member per month budget impact was estimated (commercial: $0.0008 to $0.0056; Medicare: $0.0118 to $0.0821). Capmatinib inclusion resulted in lower medical costs (commercial: -$0.0003 to -$0.0007; Medicare: -$0.0037 to -$0.0106), partially offsetting increased drug costs ($0.0011 to $0.0064; $0.0154 to $0.0928, respectively), and were primarily driven by reductions in progression and terminal care costs (-$0.0003 to -$0.0009; -$0.0037 to -$0.0125, respectively). The results were most sensitive to capmatinib market share, capmatinib price, and treatment duration. LIMITATIONS: Certain assumptions were applied to the model to account for inputs with limited evidence. CONCLUSIONS: The estimated budget impact of including capmatinib for mNSCLC with a METex14 skipping mutation is minimal, and the increased drug costs were partially offset by savings in AEs, and progression-related and terminal care costs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Idoso , Benzamidas , Orçamentos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Éxons , Humanos , Imidazóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Medicare , Mutação , Triazinas , Estados Unidos
19.
Water Res ; 186: 116415, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32927423

RESUMO

Significant effort has been made to measure and understand the surface charge of CaCO3 and Mg(OH)2 particles. Many laboratory experiments have been reported on zeta potential of natural and prepared CaCO3 and a few have also been published for Mg(OH)2, however, there are very few reported measurements of zeta potential of CaCO3 and Mg(OH)2 particles at conditions relevant to lime softening, despite lime softening being a common and established process for water treatment. The present study aims to understand the interactions and electrokinetic properties of these two particles in lime softening. Effects of various experimental parameters such as pH, temperature, aging, inorganic carbon (CO32-/HCO3-), and divalent cations (Ca2+/Mg2+) on the electrokinetic properties (i.e. zeta potential) of CaCO3 and Mg(OH)2 particles were individually studied. The interactions between humic acid (mimicking natural organic matter), silicate (representing silica), clay (mimicking suspended solids) and CaCO3/Mg(OH)2 particles were studied, as well as the interactions between CaCO3 and Mg(OH)2. Thermodynamic modeling was used to predict precipitates as a function of solution chemistry and assist with data interpretation. The results provide considerable insight into factors that are of importance to lime softening.


Assuntos
Hidróxido de Magnésio , Purificação da Água , Carbonato de Cálcio , Abrandamento da Água
20.
Drug Deliv Transl Res ; 10(5): 1203-1227, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32172351

RESUMO

Engineered immune cells offer a prime therapeutic alternate for some aggressive and frequently occurring malignancies like lung cancer. These therapies were reported to result in tumor regression and overall improvement in patient survival. However, studies also suggest that the presence of cancer cell-induced immune-suppressive microenvironment, off-target toxicity, and difficulty in concurrent imaging are some prime impendent in the success of these approaches. The present article reviews the need and significance of the currently available immune cell-based strategies for lung cancer therapeutics. It also showcases the utility of incorporating nanoengineered strategies and details the available formulations of nanocarriers. In last, it briefly discussed the existing methods for nanoparticle fuctionalization and challenges in translating basic research to the clinics. Graphical Abstract.


Assuntos
Engenharia Celular , Imunoterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Microambiente Tumoral
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