Hepatoprotective agent tethered isoniazid for the treatment of drug-induced hepatotoxicity: Synthesis, biochemical and histopathological evaluation

AbstractThe aim of the study was to investigate the protective effect of isoniazid–curcumin conjugate (INH–CRM) in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG), albumin content, and lipid peroxidation (MDA). INH–CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH–CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH–CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment

PREPARATION AND EVALUATION OF CYCLODEXTRIN COMPLEXES OF ANTI-TUBERCULAR DRUG RIFAMPICIN FOR IMPROVED BIOAVAILABILITY

The aim of the study was to increase the aqueous solubility, dissolution rate, stability, in vitro anti-tubercular activity and bioavailability of rifampicin by the way of inclusion complexation. Methyl B-cyclodextrin in case of rifampicin were used. Based on phase solubility studies that stoichiometry of complex of with respect to B-cyclodextrin for rifampicin was found to be 1:1 molar ratio. Different methods of preparation such as kneading and common solvent were employed to prepare the complexes. Formation of complexes In case of rifampicin, interaction of 4-methyl piperazin-1-ylimino-methyl (side chain) of rifampicin with the cyclodextrin molecule was confirmed by FTIR and 1H-NMR. The complexes prepared by different methods were subjected to solubility and in vitro dissolution studies. In case of rifampicin, in vitro anti-tubercular activity was found to be enhanced for the complexes of rifampicin indicated by a reduction in MIC of rifampicin. The oral bioavailability of rifampicin-MB-CD complex prepared by common solvent method was improved significantly. The results of stability studies revealed that stability of the drugs in solution and solid state were improved significantly due to complexation. Photostability of rifampicin is enhanced significantly by the way of complexation. Thus inclusion complexation of rifampicin with B-cyclodextrin, B-cyclodextrin derivatives and y-cyclodextrin improved its physical properties, bioavailability and in vitro activity

Hordeum Vulgare Hull in the Design of Fast Disintegrating Tablets

In the present study, fast disintegrating tablets were designed with a view to enhance patient compliance. In this method, the hull of Hordeum vulgare, cross carmellose sodium, and sodium starch glycolate were used as superdisintegrants (4 and 6%), along with microcrystalline cellulose and mannitol, to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on the in vitro dispersion time, the formulations were tested for the in vitro drug release pattern. Tablets having H. vulgare hull showed the release profile comparable to those tablets having sodium starch glycolate and cross carmellose sodium

Author Guide for Addressing Animal Methods Bias in Publishing

There is growing recognition that animal methods bias, a preference for animal‐based methods where they are not necessary or where nonanimal‐based methods may already be suitable, can impact the likelihood or timeliness of a manuscript being accepted for publication. Following April 2022 workshop about animal methods bias in scientific publishing, a coalition of scientists and advocates formed a Coalition to Illuminate and Address Animal Methods Bias (COLAAB). The COLAAB has developed this guide to be used by authors who use nonanimal methods to avoid and respond to animal methods bias from manuscript reviewers. It contains information that researchers may use during 1) study design, including how to find and select appropriate nonanimal methods and preregister a research plan, 2) manuscript preparation and submission, including tips for discussing methods and choosing journals and reviewers that may be more receptive to nonanimal methods, and 3) the peer review process, providing suggested language and literature to aid authors in responding to biased reviews. The author's guide for addressing animal methods bias in publishing is a living resource also available online at animalmethodsbias.org, which aims to help ensure fair dissemination of research that uses nonanimal methods and prevent unnecessary experiments on animals

Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease

Mitochondria contribute to shape intraneuronal Ca2+ signals. Excessive Ca2+ taken up by mitochondria could lead to cell death. Amyloid beta (A beta) causes cytosolic Ca2+ overload, but the effects of A beta on mitochondrial Ca2+ levels in Alzheimer's disease (AD) remain unclear. Using a ratiometric Ca2+ indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca2+ levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral beta -amyloidosis. Naturally secreted soluble A beta applied onto the healthy brain increases Ca2+ concentration in mitochondria, which is prevented by blockage of the mitochondrial calcium uniporter. RNA-sequencing from post-mortem AD human brains shows downregulation in the expression of mitochondrial influx Ca2+ transporter genes, but upregulation in the genes related to mitochondrial Ca2+ efflux pathways, suggesting a counteracting effect to avoid Ca2+ overload. We propose lowering neuronal mitochondrial Ca2+ by inhibiting the mitochondrial Ca2+ uniporter as a novel potential therapeutic target against AD. Calvo-Rodriguez et al. show elevated calcium levels in neuronal mitochondria in a mouse model of cerebral beta -amyloidosis after plaque deposition, which precede rare neuron death events in this model. The mechanism involves toxic extracellular A beta oligomers and the mitochondrial calcium uniporter

Novel membrane structure design for biomass harvesting and water recycling

Sustainable algae biofuel production is rising in demand, and the need to establish an efficient and proper algae harvesting method is extremely essential. Membrane filtration technology seems to be the most promising as a solid-liquid separation process. However, fouling seems to be the major problem for membranes. There is limited research on how to solve the problem of fouling, and cake buildup inside the membranes. A novel membrane design is required to solve the problem of fouling and cake buildup inside the membranes. The objective of this research is to construct a novel two way membrane design for algae biomass harvesting and water recycling. The methods used include culturing algae species, filtering them through the membrane module, and sample analysis for determining the water quality. The results show that the present filtration model had no fouling, or cake buildup as opposed to the previous filtration model. The present model permeate has a very low optical density of 0.007 absorbance at 750 nanometers. This result shows that permeate is completely devoid of algae.M.S

Physicochemical characterization of β-cyclodextrin and hydroxy ethyl β-cyclodextrin complexes of rifampicin

Se realizó un ensayo con el objetivo de optimizar la administración oral de rifampicina mediante la formación de complejos de inclusión con ciclodextrinas, incluida la β-ciclodextrina (β-CD) y la hidroxietil-β-ciclodextrina (HEβ- CD). El objetivo del estudio era incrementar la solubilidad y estabilidad de la rifampicina mediante la formación de complejos, y evaluar el efecto de la ciclodextrina en el tratamiento de la tuberculosis. Los estudios de solubilidad de fase mostraron que seguía una curva de solubilidad de tipo A y que la pendiente de la línea es inferior a uno, indicando la presencia de fármaco y agente aglutinante en una fracción molar de 1:1. Los complejos de ciclodextrina se prepararon mediante métodos de amasado (AM) y de disolvente común (DC). Las mezclas físicas también se prepararon en la misma proporción. En el caso de los complejos de β-CD, se observó una solubilidad dos veces mayor en el complejo preparado mediante disolvente común. Una espectometría infrarroja por transformada de Fourier (FTIR) confi rmó la formación de un complejo con (4-metil-1-piperazinil)-imino-metil de rifampicina de cadena lateral. La formación del complejo se confi rmó mediante estudios de difracción de rayos-x de polvo, microscopía electrónica de barrido (MEB) y calorimetría diferencial de barrido (CDB). Se demostró que la actividad antituberculosa in vitro de la rifampicina se vio mejorada en el caso de todos los complejos indicados mediante una reducción a la mitad de la concentración inhibitoria mínima (CIM) de rifampicina. La formación de complejos de inclusión con β-CD e hidroxietil-β-ciclodextrina mejoró sus propiedades fi sicoquímicas y su actividad antituberculosa in vitro.An attempt was made to optimize the oral delivery of rifampicin by formation of inclusion complexes with cyclodextrins including β-Cyclodextrin (β-CD), and hydroxy-ethyl-β-cyclodextrin (HEβ-CD). The aim of the study was to increase the solubility, stability of rifampicin by way of complexation and to evaluate the effect of cyclodextrin on its anti-tubercular activity. The phase solubility studies showed that it followed Type-AL solubility curve and the slope of the line is less than one, indicating 1:1 molar ratio of drug to complexing agent. Cyclodextrin complexes were prepared by kneading (KN) and common solvent (CS) methods. The physical mixtures (PM) were also prepared in the same ratio. In case of β-CD complexes, a 2 fold increase in solubility was observed with CS complex. Formation of complex with side chain 4-methyl piperazin-1-ylimino-methyl of rifampicin was confi rmed by FTIR. Formation of complex was confi rmed by DSC, SEM, and powder x-ray diffraction studies. In vitro anti-tubercular activity of rifampicin was found to be enhanced in case of all the complexes indicated by a reduction in MIC of rifampicin to half. Inclusion complexation with β-CD and hydroxy ethyl β-cyclodextrin improved its physico-chemical properties and in vitro anti-tubercular activity

Pulmonary drug delivery strategies: A concise, systematic review

Because of limitations associated with the conventional treatment of various chronic diseases a growing attention has been given to the development of targeted drug delivery systems. Pulmonary route of drug delivery gaining much importance in the present day research field as it enables to target the drug delivery directly to lung both for local and systemic treatment. Over the last 2 decades, the systemic absorption of a broad range of therapeutics after pulmonary application has been demonstrated in animals as well as in humans. This review was prepared with an aim to discuss the technical, physiological, and efficacy aspects of the novel pulmonary route of drug targeting. The review also focuses on the mechanisms of pulmonary drug administration along with compatibility of the excipients employed, devices used, and techniques of particulate dosage production. This review was prepared based on the method of extensive literature survey on the topics covering all the aspects discussed in the present subject. Hence, the better understanding of complexes and challenges facing the development of pulmonary drug delivery system offer an opportunity to the pharmaceutical scientist in minimizing the clinical and technical gaps