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1.
Toxicol Sci ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35478015

RESUMO

The 2019 United States outbreak of E-cigarette (e-cig), or Vaping, Associated Acute Lung Injury (EVALI) has been linked to presence of vitamin E-acetate (VEA) in Δ8Tetrahydrocannabinol (Δ8THC)-containing e-liquids, as supported by VEA detection in patient biological samples. However, the pathogenesis of EVALI and the complex physicochemical properties of e-cig emissions remain unclear, raising concerns on health risks of vaping. This study investigates the effect of Δ8THC/VEA e-liquids and e-cig operational voltage on in-vitro toxicity of e-cig aerosols. A novel E-cig-Exposure-Generation-System was used to generate and characterize e-cig aerosols from a panel of Δ8THC/VEA or nicotine-based e-liquids at 3.7 or 5V. Human lung Calu-3 cells and THP-1 monocytes were exposed to cell culture media conditioned with collected e-cig aerosol condensate at doses of 85 puffs/m2 and 257 puffs/m2 lung surface for 24 hours, whereafter specific toxicological endpoints were assessed (including cytotoxicity, metabolic activity, ROS generation, apoptosis and inflammatory cytokines). Higher concentrations of gaseous volatile organic compounds were emitted from Δ8THC/VEA compared to nicotine-based e-liquids, especially at 5V. Emitted PM2.5 concentrations in aerosol were higher for Δ8THC/VEA at 5V and averagely for nicotine-based e-liquids at 3.7V. Overall, aerosols from nicotine-based e-liquids showed higher bioactivity than Δ8THC/VEA aerosols in THP-1 cells, with no apparent differences in Calu-3 cells. Importantly, presence of VEA in Δ8THC- and menthol-flavoring in nicotine-based e-liquids increased cytotoxicity of aerosols across both cell lines, especially at 5V. This study systematically investigates the physicochemical and toxicological properties of a model of Δ8THC/VEA and nicotine e-cigarette condensate exposure demonstrating that pyrolysis of these mixtures can generate hazardous toxicants whose synergistic actions potentially drive acute lung injury upon inhalation.

2.
Toxicon ; 212: 19-33, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35395273

RESUMO

4-(methylthio)butyl isothiocyanate (4-MTBITC) also called erucin is abundantly present in the seeds of Eruca sativa plant closely related to cruciferous vegetables rich in isothiocyanates. We have previously reported the molecular targets of 4-MTBITC, but no acute, subacute and subchronic toxicity studies have been carried out to evaluate its safety. The non-everted gut sac method was used to study intestinal absorption and it revealed the highest absorption of 4-MTBITC in the jejunum. Dose-dependent pharmacokinetic parameters were observed in rats given 10, 20, and 40 mg/kg oral doses of 4-MTBITC. At the highest dose of 40 mg/kg, Cmax was 437.33 µg/ml and Tmax was 30 min, suggesting quick absorption and delayed elimination with elimination constant, 0.0036 ± 0.0002min-1. In a 14 days toxicity study, the mean LD50 of 4-MTBITC was 500 mg/kg body weight. After 28 and 90 days of treatment with 4-MTBITC (2.5, 10, 40 mg/kg/day), significant increases were observed in SGOT, cholesterol, and antioxidant enzymes. The levels of glycine, alanine and lysine were markedly increased in the liver tissue, thereby indicating that the liver was the target organ of 4-MTBITC induced toxicity in female animals. The histopathological examination of liver, kidney, and lung tissues revealed little focal necrosis, apoptosis, and reduction in the levels of amino acids involved in cellular metabolic pathways, indicating the anti-proliferative potential of 4-MTBITC against rapidly growing cells.


Assuntos
Apoptose , Isotiocianatos , Animais , Feminino , Isotiocianatos/toxicidade , Extratos Vegetais , Ratos
3.
J Hazard Mater ; 422: 126771, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391975

RESUMO

The present study investigates potential nanomaterial releases and occupational health risks across the lifecycle of nano-enabled building materials (NEBMs), namely, insulations and coatings. We utilized real-world degradation scenarios of a) sanding (mechanical), b) incineration (thermal), and c) accelerated UV-aging (environmental) followed by incineration. Extensive physicochemical characterization of the released lifecycle particulate matter (LCPM) was performed. The LCPM2.5 aerosol size fraction was used to assess the acute biological, cytotoxic and inflammatory effects on Calu-3 human lung epithelial cells. RNA-Seq analysis of exposed cells was performed to assess potential for systemic disease. Findings indicated that release dynamics and characteristics of LCPM depended on both the NEBM composition and the degradation scenario(s). Incineration emitted a much higher nanoparticle number concentration than sanding (nearly 4 orders of magnitude), which did not change with prior UV-aging. Released nanofillers during sanding were largely part of the matrix fragments, whereas those during incineration were likely physicochemically transformed. The LCPM from incineration showed higher bioactivity and inflammogenicity compared to sanding or sequential UV-aging and incineration, and more so when metallic nanofillers were present (such as Fe2O3). Overall, the study highlights the need for considering real-world exposure and toxicological data across the NEBM lifecycle to perform adequate risk assessments and to ensure workplace health and safety.


Assuntos
Saúde do Trabalhador , Material Particulado , Aerossóis/análise , Materiais de Construção , Humanos , Incineração , Material Particulado/toxicidade
4.
Curr Drug Deliv ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34906056

RESUMO

The conventional anticancer chemotherapies not only cause serious toxic effects, but also produce resistance in tumor cells exposed to long-term therapy. Usually, the killing of metastasized cancer cells requires long-term therapy with higher drug doses, because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and to save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist to deliver drug molecules at the specific target site and reduce the undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in the drug delivery systems, and their application in treating different cancer types in humans.

5.
Acta Bioeng Biomech ; 23(1): 45-57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34846012

RESUMO

PURPOSE: Failure of anterior cruciate ligament often occurs in young sports personnel hampering their career. Such ACL ruptures are quite prevalent in sports such as soccer during dynamic loading which occurs at more than one rate of loading. In this work, a structural constitutive equation has been used to predict the forces acting on ACL for different rates of loading. METHODS: Ligaments with distal femur and proximal tibia were subjected to tensile loading to avoid crushing of tissue ends and slipping at higher rates of strain. Custom designed cylindrical grippers were fabricated to clamp the distal femur and proximal tibial bony sections. To estimate parameters for the model, eighteen fresh cadaveric femur-ACL-tibia complex (FATC) samples were experimented on by pure tensile loading at three orders of rates of strain viz., 0.003, 0.03, and 0.3 s^-1. The experimental force-elongation data was used to obtain parameters for De-Vita and Slaughter's equation. The model was validated with additional tensile experiments. RESULTS: Statistical analysis demonstrated failure stress, Young's modulus and volumetric strain energy to vary significantly as a function of rate of strain. Midsection failure was observed only in samples tested at 0.03 s^-1. Femoral or tibial insertion failure were observed in all other experiments irrespective of rate of strain. CONCLUSION: Human FATC samples were tensile tested to failure at three rates of strain using custom-designed cylindrical grippers. A structural model was used to model the data for the ACL behaviour in the linear region of loading to predict ligament behaviour during dynamic activities in live subjects.


Assuntos
Ligamento Cruzado Anterior , Articulação do Joelho , Fenômenos Biomecânicos , Cadáver , Fêmur , Humanos , Tíbia
6.
Food Chem Toxicol ; 158: 112609, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34673181

RESUMO

Despite mounting evidence of increasing micro- and nanoplastics (MNPs) in natural environments, food, and drinking water, little is known of the potential health hazards of MNPs ingestion. We assessed toxicity and uptake of environmentally relevant MNPs in an in vitro small intestinal epithelium (SIE). Test MNPs included 25 and 1000 nm polystyrene (PS) microspheres (PS25 and PS1K); 25, 100, and 1000 nm carboxyl modified PS spheres (PS25C, PS100C, and PS1KC), and secondary MNPs from incinerated polyethylene (PEI). MNPs were subjected to 3-phase digestion to mimic transformations in the gastrointestinal tract (GIT) and digestas applied to the SIE. Carboxylated MNPs significantly reduced viability and increased permeability to 3 kD dextran. Uptake of carboxyl PS materials was size dependent, with significantly greater uptake of PS25C. Fluorescence confocal imaging showed some PS25C agglomerates entering cells independent of endosomes (suggesting diffusion), others within actin shells (suggesting phagocytosis), and many free within the epithelial cells, including agglomerates within nuclei. Pre-treatment with the dynamin inhibitor Dyngo partially reduced PS25 translocation, suggesting a potential role for endocytosis. These findings suggest that ingestion exposures to MNPs could have serious health consequences and underscore the urgent need for additional detailed studies of the potential hazards of ingested MNPs.


Assuntos
Núcleo Celular , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Microplásticos/toxicidade , Polietileno/química , Poliestirenos/toxicidade , Actinas , Transporte Biológico , Células CACO-2 , Endocitose , Exposição Ambiental/efeitos adversos , Células HT29 , Humanos , Microplásticos/metabolismo , Microesferas , Nanoestruturas , Imagem Óptica , Tamanho da Partícula , Permeabilidade , Poliestirenos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Part Fibre Toxicol ; 18(1): 33, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479598

RESUMO

BACKGROUND: Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion. METHODS: Mouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated. RESULTS: We show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low. CONCLUSIONS: Altogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity.


Assuntos
Nanopartículas Metálicas , Óxido de Zinco , Animais , Células do Cúmulo , Feminino , Nanopartículas Metálicas/toxicidade , Camundongos , Oócitos , Dióxido de Silício/toxicidade , Óxido de Zinco/toxicidade
8.
Pharm Nanotechnol ; 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496738

RESUMO

The article has been withdrawn at the request of the editor of the journal Pharmaceutical Nanotechnology due to incoherent content.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 submit-ting 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.

9.
Pharm Nanotechnol ; 9(4): 251-261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34132189

RESUMO

Aim/Objectives: Osteoarthritis (OA) is a degenerative disease of joints affecting over 7% of the world population, especially females, contributing to 2% of years lived with disability (YLD's) globally due to pain and impaired movement of limbs viz. hip, shoulder, and knee joint. The present review explores the nano-formulation approaches to improve the therapeutic efficacy of drugs for the treatment of osteoarthritis. Results and Discussion: The high treatment cost of osteoarthritis not only includes medication but also physiotherapy, adaptive aids, and devices or even surgery that further amounts to the loss of work hours. These medications are only treated symptomatically. Various nanocarriers have created interest of reasearchers in improving the bioavailability of active drugs, thereby, therapeutically improving the action and possible reduction of dose and side effects. Various nanocarriers are available viz. liposome, noisome, transferosome, hydrogel, microemulsion, and nanoparticle formulations for intraarticular, topical, and oral delivery for osteoarthritis treatment. Methods and Conclusion: This article focuses on novel approaches, such as lipid-based formulations and nano- or microparticles as treatment strategies to minimize side effects by using carriers viz. liposome, noisome, transferosome, hydrogel, microemulsion, and nanoparticle formulations for intraarticular, topical, and even oral delivery.


Assuntos
Osteoartrite , Anos de Vida Ajustados pela Incapacidade , Humanos , Hidrogéis , Osteoartrite/tratamento farmacológico
10.
Pharm Nanotechnol ; 9(3): 166-176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33888054

RESUMO

BACKGROUND: Lipid-based systems such as self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions and offer many useful drug delivery opportunities. In the modern drug discovery era, there is a constant increase in the number of poorly soluble new chemical entities that suffer from poor and erratic bioavailability problems. The oral route possesses some major disadvantages, such as lack of constant drug levels in plasma, firstpass metabolism, which results in poor bioavailability. To address these problems, various lipidbased therapeutic systems are available from which self-enanoemulsifying systems have the potential to increase the bioavailability of poorly soluble drugs. METHODS: SNEDDS is the isotropic mixture of oils, surfactant, and co-surfactant having droplet size in the range of 100-200 nm, which spontaneously emulsifies when it contacts with aqueous media in gastrointestinal (G.I) fluid. Various preparative methods are available for SNEDDS, such as high-pressure homogenizer, microfluidization, sonication, phase inversion, and shear state methods. These methods show favorable benefits in drug delivery. Self-nanoemulsifying drug delivery system possesses some disadvantages like precipitation of drug in G.I fluid or possible drug leaving in the capsule dosage form due to incompatibility issues, which can be overcome by more advanced techniques like supersaturated SNEDDS containing a precipitation inhibitor or Solid SNEDDS. These areformulated either through spray drying or using a solid carrier. CONCLUSION: The lipid-based nanocarrier (SNEDDS) plays a significant role in drug delivery to overcome the poor solubility and oral bioavailability. This review highlights the elaborative aspects of the diverse advantages of SNEDDS based formulations.


Assuntos
Sistemas de Liberação de Medicamentos , Administração Oral , Disponibilidade Biológica , Emulsões , Solubilidade
11.
Pediatr Pulmonol ; 56(6): 1389-1394, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33624927

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted via respiratory droplets, aerosols, and to a lesser extent, fomites. Defining the factors driving infectivity and transmission is critical for infection control and containment of this pandemic. We outline the major methods of transmission of SARS-CoV-2, focusing on aerosol transmission. We review principles of aerosol science and discuss their implications for mitigating the spread of SARS-CoV-2 among children and adults.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Pandemias , SARS-CoV-2 , Adulto , Aerossóis , COVID-19/prevenção & controle , Criança , Fômites , Humanos , Controle de Infecções
12.
Curr Drug Deliv ; 18(9): 1352-1367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596805

RESUMO

BACKGROUND: The present investigation attempts to optimize Supersaturable lipid based formulation (SS SMEDDS) of Biopharmaceutical Classification System (BCS) class IV drug canagliflozin (CFZ) and evaluating the oral bioavailability of the formulation. METHODS: Preliminary screening revealed Poloxamer 188 to most effectively inhibit precipitation of CFZ after dispersion during in vitro supersaturation studies. Box Behnken Design was employed for designing different formulations, and various statistical analyses were done to select an appropriate mathematical model. The optimized formulation (OSS 1) was evaluated for in vitro drug release and ex vivo permeation studies to evaluate drug release and permeation rate. Pharmacokinetic studies have been carried out according to standard methodologies. RESULTS: The optimized formulation (OSS 1) containing 781.1 mg SS SMEDDS and 2.24% w/w Poloxamer 188 was developed at a temperature of 60°C, which revealed nano-globule size with negligible aggregation. Isothermal titration calorimetry revealed the thermodynamic state of formed microemulsion with negative ΔG. The optimized formulation was observed to possess physical stability under different stress conditions and acceptable drug content. In vitro dissolution of optimized SS SMEDDS revealed a higher dissolution rate of CFZ as compared to native forms of CFZ. The permeability of CFZ from optimized SS SMEDDS across various excised segments of rat intestine was observed to be multifold higher as manifested by 2.05-fold higher Cmax and 5.64- fold higher AUC0-36h following oral administration to Wistar rats. CONCLUSION: The results could be attributed to substantial lymphatic uptake and P-glycoprotein substrate affinity of CFZ in SS SMEDDS investigated through chylomicron and P-glycoprotein inhibition approach, respectively.


Assuntos
Canagliflozina , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Disponibilidade Biológica , Emulsões , Ratos , Ratos Wistar , Solubilidade
13.
AAPS PharmSciTech ; 22(1): 24, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400035

RESUMO

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12 h) as compared with commercial tablet (3.33 ± 0.94 h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.


Assuntos
Aripiprazol/administração & dosagem , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Aripiprazol/química , Aripiprazol/farmacocinética , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões/química , Feminino , Concentração de Íons de Hidrogênio , Ratos , Ratos Sprague-Dawley
14.
IEEE Trans Vis Comput Graph ; 27(2): 1225-1235, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33048742

RESUMO

Shaded relief is an effective method for visualising terrain on topographic maps, especially when the direction of illumination is adapted locally to emphasise individual terrain features. However, digital shading algorithms are unable to fully match the expressiveness of hand-crafted masterpieces, which are created through a laborious process by highly specialised cartographers. We replicate hand-drawn relief shading using U-Net neural networks. The deep neural networks are trained with manual shaded relief images of the Swiss topographic map series and terrain models of the same area. The networks generate shaded relief that closely resemble hand-drawn shaded relief art. The networks learn essential design principles from manual relief shading such as removing unnecessary terrain details, locally adjusting the illumination direction to accentuate individual terrain features, and varying brightness to emphasise larger landforms. Neural network shadings are generated from digital elevation models in a few seconds, and a study with 18 relief shading experts found that they are of high quality.


Assuntos
Gráficos por Computador , Redes Neurais de Computação , Algoritmos , Estimulação Luminosa
15.
Curr Drug Deliv ; 18(4): 513-530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32735521

RESUMO

BACKGROUND: Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz. OBJECTIVE: The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance. METHODS: Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach. RESULTS: The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product. CONCLUSION: The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.


Assuntos
Alcinos/administração & dosagem , Benzoxazinas/administração & dosagem , Ciclopropanos/administração & dosagem , Sistemas de Liberação de Medicamentos , Administração Oral , Disponibilidade Biológica , Emulsões , Simulação de Acoplamento Molecular , Solubilidade
16.
Assay Drug Dev Technol ; 19(2): 85-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33270492

RESUMO

The aim of the study is to mechanistically investigate the drug loci, structural integrity, chemical interactions, and absorption behavior of the liquid self-microemulsifying drug delivery system (SMEDDS). The loci of drug molecules in self-forming microemulsions in biorelevant media (fasted state simulated gastric fluid and fed state simulated intestinal fluid) were investigated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Chemical interactions were observed through attenuated total reflectance spectroscopy (ATR). The structural integrity of self-forming microemulsions in biorelevant media was determined by small angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET). Morphological features of self-forming microemulsion were determined by confocal laser scanning microscopy. In vitro, lipid digestion behavior was evaluated for particle size, zeta potential, free fatty acids (FFA), and drug released through standard protocols. In-house characterizations were determined through standard methodologies. 1H and 13C NMR revealed that drug loci were found in a majority in the oily core region in the self-forming microemulsion. The ATR signifies that no inherent chemical was observed in the liquid SMEDDS and drug-loaded self-microemulsions in the biorelevant media. Structural integrity was well maintained during the dispersive and digestive phases in the gastrointestinal lumen during lipolysis in biorelevant conditions, as revealed by SAXS and FRET. An in vitro digestion study in biorelevant conditions depicts no fluctuations in size and zeta potential with a predominant release of FFA and drug, and was to be revealed physiologically acceptable for clinical applications.


Assuntos
Meios de Cultura/metabolismo , Sistemas de Liberação de Medicamentos , Lipídeos/química , Preparações Farmacêuticas/metabolismo , Química Farmacêutica , Meios de Cultura/química , Emulsões , Tamanho da Partícula , Preparações Farmacêuticas/química
17.
NanoImpact ; 22: 100325, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35559961

RESUMO

Toner-based printing equipment (TPE), including laser printers and photocopiers, utilize several engineered nanomaterials (ENMs) to improve toner performance. Operation of TPE, which rarely employ any exposure controls, generates high exposures to nanoparticles that contain ENMs and complex organics. Epidemiological literature in copier operators documents respiratory effects, including nasal blockage, cough, excessive sputum, and breathing difficulties, cardiovascular effects, oxidative stress, and inflammation. However, epidemiological studies in humans with adequate exposure assessment and dose-response analysis are lacking. We present herein the analysis of the upper airway and systemic inflammation in plasma of 19 healthy copier operators at six Singapore workplaces. We employed a repeated panel design (four biomarker measurements over two weeks) combined with a multi-marker approach (14 inflammatory cytokines in plasma and nasal lavage (NL)), and comprehensive exposure assessment using four distinct exposure metrics. We investigated spatial and temporal patterns of markers of upper airway and systemic inflammation and their association with various exposure metrics. Several inflammatory markers, namely fractalkine, IL-1ß, and IL-1α in NL, and fractalkine, IL-1ß, TNF-α, and IFN-γ in plasma, were strongly and positively associated with at least one exposure metric, whereas GM-CSF was negatively associated. The inflammation score was also strongly associated with TPE nanoparticle exposures. Exposure to TPE emissions induced moderate upper airway inflammation and stronger systemic inflammation in these healthy operators, characterized by upregulation of at least IL-1ß, fractalkine, TNF-α and IFN-γ. Proinflammatory cytokines TNF-α, IFN-γ and IL-1ß play an important role in orchestrating inflammatory responses in various clinical conditions, including cardiovascular and autoimmune disease, and likely trigger activation of endothelial cells, leading to overexpression of fractalkine, a chemokine that is involved in and associated with multiple disorders, including atherosclerosis and vascular disease. Future larger-scale epidemiological studies in these workers and consumers exposed chronically to TPE nanoparticle emissions and proactive interventions to reduce or eliminate TPE exposures are recommended.

18.
Part Fibre Toxicol ; 17(1): 40, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787867

RESUMO

BACKGROUND: Engineered nanomaterials are increasingly being incorporated into synthetic materials as fillers and additives. The potential pathological effects of end-of-lifecycle recycling and disposal of virgin and nano-enabled composites have not been adequately addressed, particularly following incineration. The current investigation aims to characterize the cytotoxicity of incinerated virgin thermoplastics vs. incinerated nano-enabled thermoplastic composites on two in vitro pulmonary models. Ultrafine particles released from thermally decomposed virgin polycarbonate or polyurethane, and their carbon nanotube (CNT)-enabled composites were collected and used for acute in vitro exposure to primary human small airway epithelial cell (pSAEC) and human bronchial epithelial cell (Beas-2B) models. Post-exposure, both cell lines were assessed for cytotoxicity, proliferative capacity, intracellular ROS generation, genotoxicity, and mitochondrial membrane potential. RESULTS: The treated Beas-2B cells demonstrated significant dose-dependent cellular responses, as well as parent matrix-dependent and CNT-dependent sensitivity. Cytotoxicity, enhancement in reactive oxygen species, and dissipation of ΔΨm caused by incinerated polycarbonate were significantly more potent than polyurethane analogues, and CNT filler enhanced the cellular responses compared to the incinerated parent particles. Such effects observed in Beas-2B were generally higher in magnitude compared to pSAEC at treatments examined, which was likely attributable to differences in respective lung cell types. CONCLUSIONS: Whilst the effect of the treatments on the distal respiratory airway epithelia remains limited in interpretation, the current in vitro respiratory bronchial epithelia model demonstrated profound sensitivity to the test particles at depositional doses relevant for occupational cohorts.


Assuntos
Poluentes Atmosféricos/toxicidade , Incineração , Nanotubos de Carbono/química , Material Particulado/toxicidade , Plásticos/toxicidade , Brônquios , Linhagem Celular , Dano ao DNA , Células Epiteliais , Estresse Oxidativo , Espécies Reativas de Oxigênio
19.
Med Drug Discov ; 7: 100051, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32835212

RESUMO

Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vitamin D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vitamin D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.

20.
J Asthma Allergy ; 13: 193-203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636652

RESUMO

OBJECTIVE: To examine predictors of spirometry use at a tertiary academic health system and association between receipt of spirometry and outcomes. PATIENTS AND METHODS: We conducted a retrospective cohort study of adult patients with an ICD-9 CM diagnostic code for asthma and a 2014 outpatient visit in either a community health center or private practice associated with a tertiary academic medical center. The main outcome was receipt of spirometry during a 2007-2015 "exposure period." We secondarily examined future hospitalizations and emergency department (ED) visits during a follow-up period (2016-2019). RESULTS: In a sample of 394 patients, the majority were white (48%; n=188) and female (72%; n=284). Mean (SD) age was 52 years. Approximately half (185, 47%) of the patients received spirometry and 25% (n=97) saw a specialist during the exposure period. Nearly, 88% (n=85) of patients who saw a specialist received spirometry. More than half of the cohort (220/394, 56%) had an ED visit or admission during the follow-up period. Of these, 168 (76.4%) had not seen a specialist and 111 (50.5%) had not received spirometry within the exposure period. We saw no association between spirometry in the exposure window and future ED visit or hospitalization. CONCLUSION: In a cohort of patients at a tertiary medical center, spirometry was underused. We observed a strong association between seeing a specialist and use of spirometry, suggesting a need to better incorporate spirometry into routine primary care for patients with asthma. Among 220 patients who had an asthma-related hospitalization or ED visit in 2016-2019, the majority had no record of receiving spirometry and no documentation indicating a prior specialist visit.

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