Physiologically Based Biopharmaceutics Modeling Coupled with Biopredictive Dissolution in Development of Bioequivalent Formulation for Mesalamine Enteric Coated Tablet: A Tough Nut to Crack.

Mesalamine is a locally acting anti-inflammatory drug used to treat mild to moderate ulcerative colitis. Because of complex formulation principle and high in vivo variability, development of bioequivalent formulation for mesalamine is challenging. Further, fed state possess significant challenges for bioequivalence (BE) due to interplay of multiple factors.

Exploring Applications of Flexible Vesicular Systems as Transdermal Drug Delivery.

Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other.

Proximity-Enabled Photochemical C-H Functionalization using a Covalent Organic Framework-Confined Fe-μ-oxo Species in Water.

Water has been recognized as an excellent solvent for maneuvering both the catalytic activity and selectivity, especially in the case of heterogeneous catalysis. However, maintaining the active catalytic species in their higher oxidation states (IV/V) while retaining the catalytic activity and recyclability in water is an enormous challenge. Herein, we have developed a solution to this problem using covalent organic frameworks (COFs) to immobilize the (EtN)[Fe(Cl)bTAML] molecules, taking advantage of the COF's morphology and surface charge.

Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease.

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of millions of people. It is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides symptomatic relief.

Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency.

Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson's disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism.

Recent developments in the synthesis of bio-inspired iron porphyrins for small molecule activation.

Nature utilizes a diverse set of tetrapyrrole-based macrocycles (referred to as porphyrinoids) for catalyzing various biological processes. Investigation of the differences in electronic structure and reactivity in these reactions have revealed striking differences that lead to diverse reactivity from, apparently, similar looking active sites. Therefore, the role of the different heme cofactors as well as the distal superstructure in the proteins is important to understand.

O reduction by iron porphyrins with electron withdrawing groups: to scale or not to scale.

Iron porphyrins are synthesized by systematically introducing electron withdrawing groups (EWGs) on pyrroles to evaluate the relationship between rate () and overpotential (). The results indicate that while EWGs lead to a rise in the thermodynamic Fe reduction potential (), the potential of the O reduction reaction (ORR) does not scale with . More importantly, the iron porphyrins with higher show an order of magnitude higher rate of ORR than unsubstituted iron tetraphenyl porphyrin.

Selectivity in Electrochemical CO Reduction.

The electrocatalytic CO reduction reaction (CORR) to generate fixed forms of carbons that have commercial value is a lucrative avenue to ameliorate the growing concerns about the detrimental effect of CO emissions as well as to generate carbon-based feed chemicals, which are generally obtained from the petrochemical industry. The area of electrochemical CORR has seen substantial activity in the past decade, and several good catalysts have been reported. While the focus was initially on the rate and overpotential of electrocatalysis, it is gradually shifting toward the more chemically challenging issue of selectivity.

DoE-based validation of a HPLC-UV method for quantification of rotigotine nanocrystals: Application to in vitro dissolution and ex vivo nasal permeation studies.

The current work is focused on optimization, development, and validation of a sensitive and specific reversed-phase high-performance liquid chromatography (RP-HPLC) method for the estimation of rotigotine (RTG) in bulk and nanoformulations. The RP-HPLC method was effectively optimized using the concepts of design of experiments. Critical method variables (CMVs) were screened using Plackett-Burman design.

A new fluorescence-based method for rapid and specific quantification of rotigotine in chitosan nanoparticles.

A new, simple, rapid and sensitive fluorescence-based method has been developed and validated for the estimation of rotigotine (RTG) in bulk and nanoformulations. RTG is a dopamine agonist approved by both the United States Food and Drug Administration and the European Medicines Agency for the treatment of Parkinson's disease and restless leg syndrome. To date, no fluorescence-based analytical method has been reported for the estimation of RTG in any pharmaceutical dosage forms.

Activating the Fe(I) State of Iron Porphyrinoid with Second-Sphere Proton Transfer Residues for Selective Reduction of CO to HCOOH via Fe(III/II)-COOH Intermediate(s).

The ability to tune the selectivity of CO reduction by first-row transition metal-based complexes via the inclusion of second-sphere effects heralds exciting and sought-after possibilities. On the basis of the mechanistic understanding of CO reduction by iron porphyrins developed by trapping and characterizing the intermediates involved ( 2015, 137, 11214), a porphyrinoid ligand is envisaged to switch the selectivity of the iron porphyrins by reducing CO from CO to HCOOH as well as lower the overpotential to the process. The results show that the iron porphyrinoid designed can catalyze the reduction of CO to HCOOH using water as the proton source with 97% yield with no detectable H or CO.

Design of Experiment (DoE)-Approach Based RP-HPLC Analytical Method Development and Validation for Estimation of Efavirenz in Bulk and Formulations.

Present study reports design of experiment (DoE) based development and validation of a simple, rapid and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method for estimation of efavirenz (EFZ), a non-nucleotide reverse transcriptase inhibitor (NNRTs), used in the treatment of acquired immunodeficiency syndrome (AIDS). Plackett-Burman design was explored to screen the critical method variables (CMVs) for the RP-HPLC method. A response surface Box-Behnken design was employed to optimize the screened CMVs which affect the analytical responses (ARs) of RP-HPLC method.

Biochemical and artificial pathways for the reduction of carbon dioxide, nitrite and the competing proton reduction: effect of 2 sphere interactions in catalysis.

Reduction of oxides and oxoanions of carbon and nitrogen are of great contemporary importance as they are crucial for a sustainable environment. Substantial research has been dedicated to these areas in the last few decades. These reductions require both electrons and protons and their thermodynamic potentials often make them compete with hydrogen evolution reaction i.

Upsurge in autophagy, associated with mifepristone-treated polycystic ovarian condition, is reversed upon thymoquinone treatment.

Polycystic ovarian syndrome (PCOS) is a multi-factorial gynecological endocrine disorder. It affects fertility in women and also predisposes to insulin resistance, type 2 diabetes mellitus, obesity etc. Earlier, significance of autophagy has been explored in PCOS-related metabolic disorders and during normal folliculogenesis.

Electrocatalytic Reduction of Nitrogen to Hydrazine Using a Trinuclear Nickel Complex.

Activation and reduction of N have been a major challenge to chemists and the focus since now has mostly been on the synthesis of NH. Alternatively, reduction of N to hydrazine is desirable because hydrazine is an excellent energy vector that can release the stored energy very conveniently without the need for catalysts. To date, only one molecular catalyst has been reported to be able to reduce N to hydrazine chemically.

Hyaluronan-binding protein 1 (HABP1) overexpression triggers induction of senescence in fibroblasts cells.

Hyaluronan-binding protein 1 (HABP1), a multi-compartmental, multi-functional protein has a wide range of functions, which can be attributed to its ability to associate with a variety of cellular ligands. Earlier we have reported that HABP1 overexpression in rat normal fibroblasts (F-HABP07) shows chronic generation of reactive oxygen species (ROS), induction of autophagy, and apoptosis. However, a significant proportion of cells remained viable after the majority went through apoptosis from 60 to 72 h.

Drug Permeation against Efflux by Two Transporters.

The development of new antibiotics against Gram-negative bacteria is hampered by the powerful protective properties of their cell envelope. This envelope consists of two membranes augmented by efflux transporters, which act in synergy to restrict cellular access to a broad range of chemical compounds. Recently, a kinetic model of this system has been constructed.

Synthetic Iron Porphyrins for Probing the Differences in the Electronic Structures of Heme a, Heme d, and Heme d.

A variety of heme derivatives are pervasive in nature, having different architectures that are complementary to their function. Herein, we report the synthesis of a series of iron porphyrinoids, which bear electron-withdrawing groups and/or are saturated at the β-pyrrolic position, mimicking the structural variation of naturally occurring hemes. The effects of the aforementioned factors were systematically studied using a combination of electrochemistry, spectroscopy, and theoretical calculations with the carbon monoxide (CO) and nitric oxide (NO) adducts of these iron porphyinoids.

Multi-functional, multicompartmental hyaluronan-binding protein 1 (HABP1/p32/gC1qR): implication in cancer progression and metastasis.

Cancer is a complex, multi-factorial, multi-stage disease and a global threat to human health. Early detection of nature and stage of cancer is highly crucial for disease management. Recent studies have proved beyond any doubt about the involvement of the ubiquitous, myriad ligand binding, multi-functional human protein, hyaluronan-binding protein 1 (HABP1), which is identical to the splicing factor associated protein (p32) and the receptor of the globular head of the complement component (gC1qR) in tumorigenesis and cancer metastasis.

Tenofovir disoproxil fumarate loaded PLGA nanoparticles for enhanced oral absorption: Effect of experimental variables and in vitro, ex vivo and in vivo evaluation.

In this study, PLGA based nanoparticles of tenofovir disoproxil fumarate (TDF) were designed for enhancing its oral absorption. To develop PLGA based TDF nanoparticles with the goal of minimum particle size and maximum entrapment efficiency statistical optimization techniques (factorial design and response surface methodology) were employed. The optimized nanoparticles were characterized for size, shape, charge and physical state.

Oral pharmacokinetic interaction of ester rich fruit juices and pharmaceutical excipients with tenofovir disoproxil fumarate in male Wistar rats.

1. The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF). 2.

Reversible thermal unfolding of a yfdX protein with chaperone-like activity.

yfdX proteins are ubiquitously present in a large number of virulent bacteria. A member of this family of protein in E. coli is known to be up-regulated by the multidrug response regulator.

Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi.

The yfdX family proteins are known for long time to occur in various virulent bacteria including their multidrug resistant (MDR) strains, without any direct assigned function for them. However, yfdX protein along with other proteins involved in acid tolerance response is reported to be up regulated by the multidrug response regulatory system in E. coli.

In vivo role of Candida albicans β-hexosaminidase (HEX1) in carbon scavenging.

The capability to utilize of N-acetylglucosamine (GlcNAc) as a carbon source is an important virulence attribute of Candida albicans. But there is a lack of information about the in vivo source of GlcNAc for the pathogen within the host environment. Here, we have characterized the GlcNAc-inducible β-hexosaminidase gene (HEX1) of C.