Birla Institute of Technology and Science

About: Birla Institute of Technology and Science is a education organization based out in Pilāni, Rajasthan, India. It is known for research contribution in the topics: Computer science & Population. The organization has 8897 authors who have published 13947 publications receiving 170008 citations.

Microneedle-based drug delivery: materials of construction

Abstract: Microneedle-based drug delivery has attracted researchers’ attention over the last decade. The material of construction of microneedles has emerged as a critical factor influencing clinical usage, manufacture, drug loading and drug stability. Initially, microneedles were fabricated using glass, silicon and metals. The development of sophisticated machining tools and advances in the polymer science allowed for a major shift in materials of construction of microneedles towards polymeric systems. Delivery of difficult to formulate therapeutics, including proteins, peptides, vaccines and genetic material has been established using microneedles. There is a constant search for newer materials, which can easily form microneedles with sufficient strength to penetrate biological barriers, can be easily manufactured, and are compatible with drug molecules and biological systems. While several reviews have discussed microneedle-based cosmetic and drug delivery applications, there is a gap in understanding the effect of material of construction of microneedles on drug stability and potential for large-scale manufacture. This review is an attempt to present microneedles as a function of the material used for its construction. Since microneedle commercialization is now a realistic possibility, we believe that improved understanding of materials and their chemistry will allow for improved decision making, especially for industries looking towards bringing microneedle technology to manufacturing setups. Microneedles (MN) bypass the superficial skin layers to deliver molecules to deeper tissues. The material of MN construction has emerged as a critical factor influencing cost, clinical usage, manufacture, drug loading and drug stability. Currently available materials and techniques for MN fabrication and their relevance to scale-up are reviewed.

Constraints on a Bianchi type I spacetime extension of the standard Λ CDM model

Abstract: We consider the simplest anisotropic generalization, as a correction, to the standard $\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ model, by replacing the spatially flat Robertson-Walker metric by the Bianchi type-I metric, which brings in a new term ${\mathrm{\ensuremath{\Omega}}}_{\ensuremath{\sigma}0}{a}^{\ensuremath{-}6}$ (mimicking the stiff fluid) in the average expansion rate $H(a)$ of the Universe. From Hubble and Pantheon data, relevant to the late Universe ($z\ensuremath{\lesssim}2.4$), we obtain the constraint ${\mathrm{\ensuremath{\Omega}}}_{\ensuremath{\sigma}0}\ensuremath{\lesssim}{10}^{\ensuremath{-}3}$, in line with the model-independent constraints. When the baryonic acoustic oscillations and cosmic microwave background (CMB) data are included, the constraint improves by 12 orders of magnitude, i.e., ${\mathrm{\ensuremath{\Omega}}}_{\ensuremath{\sigma}0}\ensuremath{\lesssim}{10}^{\ensuremath{-}15}$. We find that this constraint could alter neither the matter-radiation equality redshift nor the peak of the matter perturbations. Demanding that the expansion anisotropy has no significant effect on the standard big bang nucleosynthesis (BBN), we find the constraint ${\mathrm{\ensuremath{\Omega}}}_{\ensuremath{\sigma}0}\ensuremath{\lesssim}{10}^{\ensuremath{-}23}$. We show explicitly that the constraint from BBN renders the expansion anisotropy irrelevant to make a significant change in the CMB quadrupole temperature, whereas the constraint from the cosmological data in our model provides the temperature change up to $\text{\ensuremath{\sim}11 mK}$, though it is much beyond the CMB quadrupole temperature.

N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo.

Abstract: During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT) against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV), Dengue-2 (Den-2) and West Nile viruses (WNV). Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV) and West Nile virus (WNV) replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50) produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM) and 4 μgm/ml (0.000006 μM) respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100%) prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder accounting for 60–80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylatio...