Formulation development and characterization of lamotrigine-salicylic acid crystalline product: A strategy to improve oral release of drug for better management of epilepsy

356-362Lamotrigine, a FDA approved antiepileptic drug is widely used in the treatment of epilepsy and bipolar disorder. However, poor aqueous solubility and low dissolution rate limit its oral absorption leading to a delayed onset of action with reduced therapeutic effect. The present study aims for the development of formulation and characterization of lamotrigine-salicylic acid crystalline product for the improvement of oral release and absorption for better management of epilepsy. The crystalline product of LT are developed with SA at 1:1, 2:1, 3:1 molar ratios by solvent evaporation method. The experimental crystals have been characterized by different analytical techniques such as fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) etc. Presence of characteristic peaks for peptide in the experimental crystalline products in FTIR spectra indicates formation of strong covalent bond between LA and SA. In the DSC thermograms, melting endotherm of the formulations showed different melting points than pure LT. PXRD data depicted sharp peaks for the formulations, which further justified the successful formation of a new crystalline phase. Dissolution profile of the experimental crystal (L1S1 at 1:1 molar ratio) in simulated gastric fluid was higher than that of the pure drug and other formulations. The optimized crystalline product of LT may be used for the better oral treatment of epilepsy with early onset of action after successful in vivo studies

Recent Advancements in Phyto Component Based Nanocarriers for Improved Treatment of Brain Disorders

Effective treatment of brain disorders remains a tough task in medical science. Age-old brain disorders like Parkinson’s (PD) and Alzheimer’s (AD) are yet to be managed effectively in spite of fabulous scientific progress over the last decades. Presently available treatment strategies have been found insufficient to tackle the out bursting cases of AD and PD. Indeed, presence of blood-brain barrier (BBB) highly hijacks success of conventional drug therapy. In this regard, phyto bioactive components delivered through nanocarrier (NCs) systems hold ray of hope in improving treatment benefits in brain disorders. Several NCs including polymeric nanoparticles, nanoliposomes, micelles, dendrimers have now being heavily researched to effectively deliver the phyto active components to brain tissue. NCs owing to their structural and physiological uniqueness have now been evolved with great potential for the treatment of brain disorders. Functionalization of brain specific ligands on the surface of NCs further makes them target specific, which might significantly improve bioavailability or reduce the off-target adverse effects. This chapter primarily focuses on recent advancements in phyto component loaded NCs employed for the treatment of brain disorders. The chapter especially covers existing impediments of phyto component based NCs for Parkinson and Alzheimer’s disease

COVID‐19 vaccines and their underbelly: Are we going the right way?

Abstract Background Historically, a critical aetiological agent of health concern stays till eternity after its discovery, so shall it be with the COVID‐19 outbreak. It has transformed human life to a ‘new normal’ with huge tolls on the social, psychological, intellectual and financial spheres. Aim This perspective aimed to collate numerous reported COVID‐19 vaccine‐associated adverse events and the predisposing factors. It focussed on the efficacy of mix‐n‐match (cocktail) vaccines to effectively counter COVID‐19 infection to facilitate future research and possible interventions. Material and Methods Databases like Scopus, Pubmed and the Web‐of‐science were searched for published literature on ‘adverse events associated with COVID‐19 vaccine’. The reports and updates from health agencies like the WHO and CDC were also considered for the purpose. The details with respect to the adverse events associated with COVID‐19 vaccination and the predisposing factors were compiled to obtain insights and suggest possible future directions in vaccine research. Results India stood strong to manage its health resources in time and turned into a dominant global vaccine supplier at a time when healthcare infrastructure of many countries was still significantly challenged. Developing indigenous vaccines and the vaccination drive in India were its major achievements during the second and the subsequent COVID‐19 waves. The fully indigenous Covaxin vaccine, primarily as an emergency intervention, was successfully rapidly launched. Similar such vaccines for emergency use were developed elsewhere as well. However, all of these reached the marketplace with a ‘emergency use only’ tag, without formal clinical trials and other associated formalities to validate and verify them as these would require much longer incubation time before they are available for human use. Discussion Many adverse events associated with either the first or the second/booster vaccination doses were reported. Evidently, these associated adverse events were considered as ‘usually rare’ or were often underreported. Without the additional financial or ethical burden on the vaccine companies, fortunately, the Phase IV (human) clinical trials of their manufactured vaccines are occurring by default as the human population receives these under the tag ‘emergency use’. Thus, focused and collaborative strategies to unveil the molecular mechanisms in vaccine‐related adverse events in a time‐bound manner are suggested. Conclusion Reliable data particularly on the safety of children is lacking as majority of the current over‐the‐counter COVID‐19 vaccines were for emergency use. Many of these were still in their Phase III and Phase IV trials. The need for a mutant‐proof, next‐gen COVID‐19 vaccine in the face of vaccine‐associated adverse events is opined

Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response

Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response. Several nucleic acid‐sensing pathways leading to interferon‐stimulated gene expression are highly activated in IRGM knockout mice and human cells. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG‐I, and mediates their p62‐dependent autophagic degradation to restrain interferon signaling. Further, IRGM deficiency results in defective mitophagy leading to the accumulation of defunct leaky mitochondria that release cytosolic DAMPs and mtROS. Hence, IRGM deficiency increases not only the levels of the sensors, but also those of the stimuli that trigger the activation of the cGAS‐STING and RIG‐I‐MAVS signaling axes, leading to robust induction of IFN responses. Taken together, this study defines the molecular mechanisms by which IRGM maintains interferon homeostasis and protects from autoimmune diseases

Venn diagram showing distribution of participants according to the different outcomes groups.

<p>Venn diagram showing distribution of participants according to the different outcomes groups.</p

Univariate analysis among women who use reusable cloth pads (N = 249) comparing the odds of different MHM practices for washing, drying and storing cloth pads among BV or UTI laboratory confirmed cases and BV or UTI laboratory negative controls (excluding symptomatic controls) (Group 4).

<p>*OR, odds ratio; CI, confidence interval, no = number.</p><p>Denominators vary as not all respondents answered all questions.</p><p>Univariate analysis among women who use reusable cloth pads (N = 249) comparing the odds of different MHM practices for washing, drying and storing cloth pads among BV or UTI laboratory confirmed cases and BV or UTI laboratory negative controls (excluding symptomatic controls) (Group 4).</p

Univariate analysis assessing association between demographics characteristic of women participating in the study according to symptomatic status.

<p>*OR, odds ratio; CI, confidence interval, SD (standard deviation)</p><p>Univariate analysis assessing association between demographics characteristic of women participating in the study according to symptomatic status.</p

Definition of case-control outcomes groups.

<p>Definition of case-control outcomes groups.</p