FORMULATION DEVELOPMENT AND EVALUATION OF TEMOZOLOMIDE LOADED HYDROGENATED SOYA PHOSPHATIDYLCHOLINE LIPOSOMES FOR THE TREATMENT OF BRAIN CANCER

Objective: The objective of this study was to encapsulate temozolomide (TMZ) in the liposomal formulation for the treatment of glioblastoma. TMZis one of the most effective substances in vitro against cells derived from glioblastoma. However, it may not have a significant effect in vivo due topoor penetration in brain which may be attributed to the blood-brain-barrier. The main objective of this investigation is to develop a liposomal drugdelivery system which could improve the brain targeting, and solve the treatment-related problems.Methods: In this study, TMZ loaded liposomes were prepared by ethanol injection method. The characterization of formulated liposomes was carriedout by vesicle size, entrapment efficiency, surface morphology, and in vitro drug release study. The prepared liposomes were also evaluated for celluptake and cell cytotoxicity studies.Results: Particle size and entrapment efficiency were found to be 105.7±3.9 nm and 78.25±0.98%, respectively. 75% of the entrapped drug wasreleased in 24 hrs from the selected liposomal formulation. Cell uptake study reveals that hydrogenated soya phosphatidylcholine (HSPC) loaded TMZliposomes interact with the glioblastoma cells and kill the cancer cells effectively. Cytotoxicity assay confirms that drug loaded HSPC liposomes aremore efficient with respect to killing of glioblastoma cells as compared to plain drug.Conclusion: These results suggest that the TMZ loaded HSPC liposome may serve as a proficient targeted drug delivery system for the effectivemanagement of glioblastoma.Keywords: Temozolomide, Liposomes, Hydrogenated soya phosphatidylcholine, Cholesterol, Glioblastoma

PREPARATION, CHARACTERIZATION, AND OPTIMIZATION OF MEBENDAZOLE SPHERICAL AGGLOMERATES USING MODIFIED EVAPORATIVE PRECIPITATION IN AQUEOUS SOLUTION (EPAS)

Objective: Mebendazole is a popular benzimidazole class anthelmintic drug useful in the treatment of main infections of threadworms as well as other less common worm infections like whipworm, roundworm, and hookworm in adults and children over 2 y of age. It is poorly soluble in water resulting in poor absorption from the intestinal tract leading to a decrease in bioavailability. Moreover, Mebendazole has poor flowability due to the needle-shaped crystals. This work was carried out with the aim of increasing the flowability and solubility of Mebendazole. Methods: A 32 full factorial design was used to investigate the effect of the concentration of Mebendazole and the quantity of water as an external phase using evaporative precipitation into an aqueous solution. The prepared agglomerates were characterized for particle size distribution, shape, Hausner ratio, Carr’s index and % dissolved in 60 min (C60).   Results: The prepared agglomerates were found to be monodispersed. They also showed a decrease in the Hausner ration and Carr’s index, indicating improved flowability. Increase in C60 indicated that the agglomerates were found to have increased water solubility. Conclusion: Scanning Electron Microscopy showed that the agglomerates were spherical in shape. Fourier Transformed Infra-Red studies showed no chemical change in the prepared spherical agglomerates. Differential Scanning Calorimetry and X-ray diffraction studies showed an increase in amorphous characteristics of prepared spherical agglomerates. This method may be used for drugs with similar characteristics as Mebendazole

A Photovoltaic Module Diagnostic Setup for Lock-in Electroluminescence Imaging

Electroluminescence (EL) imaging and infrared (IRT) thermography techniques have become indispensable tools in recent years for health diagnostic of photovoltaic modules in solar industry application. We propose a diagnostic setup, which performs lock-in EL for accurate analysis of different types of faults occurring in a solar module. The setup is built around a high-speed SWIR camera, which can acquire images at very short integration time (1μs) and high frame rate (301 fps). In addition, a state-of-the-art imaging chamber allows for introducing controlled levels of ambient light noise for developing new light noise removal methods, rotation of panel frame in 3 axes plane for developing perspective distortion correction techniques. The paper also gives an insight of different system and communication delays that affects the performance of overall EL lock-in imaging system integration. The purpose of the diagnostic setup is to support research in PV failure quantification through EL imaging, which can also be useful for aerial drone imaging of PV plants.</p

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Dissolution enhancement of albendazole through nanocrystal formulation

Albendazole, a BCS class II drug, has poor dissolution characteristic. In order to enhance dissolution nanocrystals were prepared by antisolvent precipitation process using PVP K-30(0.05%,0.1%,0.2%,0.4%) as stabilizer. The process was optimized in terms of concentration of stabilizer(PVP K 30) in order to enhance dissolution and obtain stable particles with a small mean particle size. Nanocrystals were characterized with respect to particle size, in vitro dissolution and X-ray diffraction pattern. Decrease in particle size of nanocrystals was observed with increase in concentration of stabilizer. Dissolution of nanocrystals also improved with increase in concentration of PVP K-30. Crystalline state evaluation before and following particle size reduction was conducted through XRD to denote any possible transformation to an amorphous state during process

Formulation and optimization of piroxicam proniosomes by 3-factor, 3-level box-behnken design

The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of piroxicam proniosomes by the slurry method. A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation and construct contour plots to predict responses. The independent variables selected were molar ratio of Span 60:cholesterol (X1), surfactant loading (X2), and amount of drug (X3). Fifteen batches were prepared by the slurry method and evaluated for percentage drug entrapment (PDE) and vesicle size. The transformed values of the independent variables and the PDE (dependent variable) were subjected to multiple regression to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation to derive a reduced-model polynomial equation to predict the PDE of proniosome-derived niosomes. Contour plots were constructed to show the effects of X1, X2 and X3 on the PDE. A model was validated for accurate prediction of the PDE by performing checkpoint analysis. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0, −0.158 and -0.158 respectively), for maximized response of PDE with constraints on vesicle size. The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of piroxicam proniosomes

Poly(D,L-Lactide-Co-Glycolide) microspheres containing 5-fluorouracil: Optimization of process parameters

The objective of this research was to optimize the processing parameters for poly(D,L-lactide-coglycolide) (PLGA) microspheres of 5-fluorouracil (5-FU) and to mathematically relate the process parameters and properties of microspheres. Microspheres were prepared by a water-in-oil-in-water emulsion solvent evaporation technique. A 32 factorial design was employed to study the effect of the volume of the internal phase of the primary emulsion and the volume of the external phase of the secondary emulsion on yield, particle size, and encapsulation efficiency of microspheres. An increase in the volume of the internal phase of the primary emulsion resulted in a decrease in yield and encapsulation efficiency and an increase in particle size of microspheres. When the volume of the external phase of the secondary emulsion was increased, a decrease in yield, particle size, and encapsulation efficiency was observed. Microspheres with good batch-to-batch reproducibility could be produced. Scanning electron microscopic study indicated that microspheres existed as aggregates