Novel flavonoid-based biodegradable nanoparticles for effective oral delivery of etoposide by P-glycoprotein modulation: an in vitro,ex vivo and in vivo investigations

Abstract

A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide?+?quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.     

Isolation and characterization of degradation impurities in docetaxel drug substance and its formulation

The degradation of docetaxel drug substance and its injection formulation has been investigated. The majority of impurities were observed in a base degradation study and all five degradation products were characterized. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, these were characterized as 10-deacetyl baccatin III, 7-epi-10-deacetyl baccatin III, 7-epi-10-oxo-10-deacetyl baccatin III, 7-epi docetaxel and 7-epi-10-oxo-docetaxel, respectively. The last two impurities were also detected in the stability study of docetaxel formulation. Out of these degradation impurities two substances have been previously identified while the other three previously unreported.     

Evaluation of hearing loss in tympanic membrane perforation

To evaluate and analyse the hearing loss in tympanic membrane perforation based on size, site and duration of perforation. The material for this study was comprised of 100 patients of either sex and of age 15?years and above selected randomly. Size of tympanic membrane perforation was assessed under microscope using calibrated wire look. Patients were divided into three groups according to size; group I (0-9?mm(2)), Group II (9-30?mm(2)), Group III (≥?30?mm(2)); according to site into anterior and posterior group; according to involvement of malleus into malleolar and non malleolar and according to duration into Group A (<1?year), Group B (1-5?years), Group C (≥?5?years). Hearing loss was measured in each case with pure tone audiometry. Data was analysed statistically using paired t-test. Hearing loss increased as the perforation size increased [I vs. II (t?-?4.23, p??0.05). Hearing loss was more in malleolar perforation (t?-?5.74, p?相似文献   

Ciliary Muscle Dimension Changes With Accommodation Vary in Myopia and Emmetropia

PurposeThe purpose of this study was to determine whether accommodation-induced changes in ciliary muscle dimensions vary between emmetropes and myopes, and the effect of the image analysis method.MethodsSeventy adults aged 18 to 27 years consisted of 25 people with emmetropia (spherical equivalent refraction [SER] +0.21 ± 0.36 diopters [D]) and 45 people with myopia (−2.84 ± 1.72 D). There were 23 people with low myopia (>−3 D) and 22 people with moderate myopia (−3 to −6 D). Right eye ciliary muscles were imaged (Visante OCT; Carl Zeiss Meditec) at 0 D and 6 D demands. Measures included ciliary muscle length (CML), ciliary muscle curved length (CMLarc), maximum ciliary muscle thickness (CMTmax), CMT1, CMT2, and CMT3 (fixed distances 1–3 mm from the scleral spur), CM25, CM50, and CM75 (proportional distances 25%–75%). Linear mixed model analysis determined effects of refractive groups, race, and demand on dimensions. Significance was set at P < 0.05.ResultsMyopic eyes had greater CML and CMLarc nasally than emmetropic eyes. Myopic eyes had thicker muscles than emmetropic eyes at nasal positions, except CM25 and CMT3, and at CM75 temporally. During accommodation and only nasally, CML reduced in emmetropic and myopic eyes, and CMLarc reduced in myopic eyes only. During accommodation, both nasally and temporally, muscles thickened anteriorly (CMT1 and CM25) and thinned posteriorly (CMT3 and CM75) except for temporal CM75. Moderate myopic eyes had greater temporal CMLarc than low myopic eyes, and the moderate myopes had thicker muscles both nasally and temporally using fixed and proportional distances.ConclusionsPeople with myopia had longer and thicker ciliary muscles than people with emmetropia. During accommodation, the anterior muscle thickened and the curved nasal muscle length shortened, more in myopic than in emmetropic eyes. The fixed distance method is recommended for repeat measures in the same individual. The proportional distance method is recommended for comparisons between refractive groups.     

Anti-obesity and hypoglycemic effect of ethanolic extract of Murraya koenigii (L) leaves in high fatty diet rats

ObjectiveTo evaluate the hypoglycemic and anti-obesity activities of of Murraya koenigii leaves.MethodThe study was performed in high fatty diet induced obesity rats. After 15 days baseline period the treatments animals were received ethanolic extract of Murraya koenigii leaves (300 and 500 mg/kg) in high fatty diet rats. All the treatments were given for one month. On 30th day all the fasted animals received an intraperitoneal injection of glucose (1 g/kg) for glucose tolerance test. At the end of study body weight, total cholesterol, triglycerides, and blood glucose level were measured.ResultsThe results demonstrate clearly that repeated oral administration of Murraya koenigii leaves evoked a potent anti-hyperglycaemic activity in high fat diet obese rats. Postprandial hyperglycaemic peaks were significantly lower in plant-treated experimental groups. In other hand, high fatty diet group increased the both total cholesterol and triglycerides levels as compared to control group. While administration of Murraya koenigii leaves significantly decreased in both cholesterol as well as triglycerides.ConclusionsWe can conclude that Murraya koenigii leaves evokes potent anti-hyperglycaemic and anti-obesity effects. This fact could support their use by the diabetes patient for controlling body weight as well as maintains the glycemic level.     

Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica infection in Bangladeshi children

BACKGROUND: The association of antibody responses with both innate and acquired immunity to amebiasis indicate that CD4+ T cells play a role in protection against Entamoeba histolytica infection. To test this hypothesis, we compared the genotype frequencies of human leukocyte antigen (HLA) class II alleles in a cohort of Bangladeshi children intensively monitored for E. histolytica infection for a 3-year period. METHODS: Using logistic regression, we calculated the odds of disease by genotype and by haplotype. RESULTS: The DQB1*0601 heterozygous and homozygous genotypes were found in 55% of E. histolytica-negative children but in only 34% of E. histolytica-positive children (overall odds ratio, 2.39; 95% confidence interval [CI], 1.26-4.54). Children who were heterozygous for the DQB1*0601/DRB1*1501 haplotype were 10.1 times (95% CI, 2.02-50.6) more likely to be both E. histolytica negative and serum anti-lectin immunoglobulin G negative at baseline. Other DQB1 and DRB1 alleles (DQB1*0202, DQB1*0301, and DRB1*0701) were not associated with any of the clinical outcomes related to amebiasis. CONCLUSION: A potential protective association was observed with the HLA class II allele DQB1*0601 and the heterozygous haplotype DQB1*0601/DRB1*1501. This association may explain why amebiasis does not occur in some children who are exposed to the parasite and implicates HLA class II-restricted immune responses in protection against E. histolytica infection.     

Structural,thermal, and transport properties of La0.67Sr0.33MnO3 nanoparticles synthesized via the sol–gel auto-combustion technique

Herein, rare-earth manganite, La_0.67Sr_0.33MnO₃, has been prepared by a citric acid-assisted sol–gel auto-combustion method at a maintained pH value of 11. Room-temperature X-ray diffraction (RT-XRD) data analysis revealed a rhombohedral structure for the sample with the space group R3c, which was further confirmed by synchrotron radiation X-ray diffraction (SR-XRD). Rietveld refinement was carried out for both spectra, which confirmed the SR-XRD and RT-XRD results and the various structural parameters. To determine any of the phase transitions in the sample, temperature-dependent X-ray diffraction corresponding to the temperatures of 100 K, 200 K, 250 K, and 325 K was carried out, and no new phase was found. Temperature-dependent Raman characterization confirmed the metallic phase of the sample with the reduced Jahn–Teller distortion. Scanning electron microscopy confirmed the growth in the grain size as a result of a high sintering temperature. Compositional verification was conducted using energy-dispersive analysis of X-ray diffraction (EDAX). Low-temperature dc resistivity measurement showed a metal-insulator transition temperature (T_MI) of ≈178 K. The DSC-specific heat measurement shows the ferromagnetic metallic nature where heat capacity increases with an increase in temperature.

Herein, rare-earth manganite, La_0.67Sr_0.33MnO₃, has been prepared by a citric acid-assisted sol–gel auto-combustion method at a maintained pH value of 11.     

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.