Next-Generation Nanoparticle-Enabled mRNA Vaccines in the Treatment of COVID-19.

The emergence of messenger ribonucleic acid (mRNA) vaccines as an alternative platform to traditional vaccines has been accompanied by advances in nanobiotechnology, which have improved the stability and delivery of these vaccines through novel nanoparticles (NPs). Specifically, the development of NPs for mRNA delivery has facilitated the loading, protection and release of mRNA in the biological microenvironment, leading to the stimulation of mRNA translation for effective intervention strategies. Intriguingly, two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have been permitted for emergency usage authorization to prevent COVID-19 infection by USFDA.

Development of a Supercritical Fluid Extraction Process for Preparation of Phytosteroids Rich Extract From Tinospora cordifolia Stem and Determination of Content of Three Phytosteroids Using a Validated Ultra-High Performance Liquid Chromatography Method.

Tinospora cordifolia is an integral part of traditional medicine, rich in secondary metabolites of various chemical classes including phytosteroids. These phytosteroids possess cholesterol-lowering property; however, systematic studies are lacking regarding preparation of extract enriched with such bioactive compounds. In this study, supercritical fluid extraction (SFE) method was developed to obtain three phytosteroids (ecdysterone, stigmasterol, and β-sitosterol) enriched extract from T.

Intelligently Actuating Dual-Barrier Hyaluronic Acid-Functionalized Inflammation-Responsive Nanohydrogel for Targeted Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune condition marked by persistent synovial inflammation, cartilage degradation, and progressive joint dysfunction. Current intra-articular glucocorticoid therapies, though effective, are limited by rapid drug clearance, systemic side effects, and the need for repeated dosing. To overcome these limitations, we developed an inflammation-responsive, dual-barrier nanohydrogel system (Dex-LNP-HG) for sustained and targeted intra-articular delivery of dexamethasone (Dex).

Targeted Nasal Route Delivery of Cationic Anti-TB Drug-Loaded Nano-embedded Microparticles for Mycobacterial Elimination in the CNS.

Central nervous system tuberculosis (CNS-TB) is a severe and insidious form of extrapulmonary tuberculosis (TB) associated with a high mortality rate, often leading to fatal outcomes or debilitating neurological impairments. The therapeutic regimen for CNS-TB follows an approach similar to that of pulmonary TB but faces significant challenges in effectively reaching the cerebrospinal fluid and achieving therapeutic drug levels in the brain and surrounding fluids. A major obstacle in CNS-TB treatment is the difficulty in permeating the blood-brain barrier (BBB).

Pharmacokinetic and Pharmacodynamics of Clofazimine Nano-in-Microparticles: Enhanced Brain Delivery and CNS Tuberculosis Amelioration via Intranasal Administration.

(Mtb) demonstrates a proclivity for infecting extrapulmonary sites, notably the brain. Treating these extrapulmonary tuberculosis (TB) manifestations is challenging due to the difficulty of drug delivery across the blood-brain barrier. Clofazimine (CLF) has exhibited promising activity against Mtb, including multidrug-resistant variants, in vitro and in preclinical animal models.

Host-Directed Therapy with Inhalable Lovastatin Microspheres for Matrix Metalloproteinase Inhibition in Tuberculosis.

Tuberculosis (TB) triggers a robust immune response, which leads to significant destruction of the lung tissue at the site of infection, aiding in the transmission of (Mtb) to the hosts. The excessive inflammatory response contributes heavily to extracellular matrix (ECM) damage, which is linked to high mortality rates among TB patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are pivotal in the breakdown of the ECM, worsening tissue destruction.

Multi-Targeting Phytochemicals for Alzheimer's Disease.

Alzheimer's disease (AD) is a type of neurodegenerative illness in which β-amyloid (Aβ) and tau protein accumulate in neurons in the form of tangles. The pathophysiological pathway of AD consists of Aβ-amyloid peptides, tau proteins, and oxidative stress in neurons and increased neuro-inflammatory response. Food and Drug Administration in the United States has authorized various drugs for the effective treatment of AD, which include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, and aducanumab.

Digital supportive supervision (DiSS) of maternal health, child health and nutrition (MCHN) service delivery in Rajasthan, India: study protocol for impact evaluation and cost-effectiveness analysis.

Background: A digital supportive supervision (DiSS) tool was developed and implemented in Rajasthan, India, to enhance the coverage and quality of maternal health, child health and nutrition (MCHN) services. This study aims to assess the impact and cost-effectiveness of DiSS compared to traditional paper-based supportive supervision.

Methods And Analysis: A quasi-experimental research design incorporating interrupted time series regression analysis will be employed to evaluate the impact of DiSS.

Trans-nasal brain delivery of anti-TB drugs by methyl-β-cyclodextrin microparticles show efficient mycobacterial clearance from central nervous system.

Central nervous system tuberculosis (CNS-TB) is the most severe extra-pulmonary manifestation of tuberculosis (TB), facing significant challenges due to the limited penetration of anti-TB drugs (ATDs) across the blood-brain barrier (BBB) and their insufficient concentrations at the site of infection. This study aimed to enhance the efficacy of ATDs by encapsulating them in methyl-β-cyclodextrin (M-β-CD) microparticles (ATD-MP) using spray drying, intended for intranasal delivery to manage CNS-TB. M-β-CD microparticles loaded with isoniazid (INH) and rifampicin (RIF) exhibited spherical shapes with slightly deflated surfaces and particle sizes of 6.

Inhalable chitosan-coated nano-assemblies potentiate niclosamide for targeted abrogation of non-small-cell lung cancer through dual modulation of autophagy and apoptosis.

Lung carcinoma, particularly non-small-cell lung cancer (NSCLC), accounts for a significant portion of cancer-related deaths, with a fatality rate of approximately 19 %. Niclosamide (NIC), originally an anthelmintic drug, has attracted attention for its potential in disrupting cancer cells through various intracellular signaling pathways. However, its effectiveness is hampered by limited solubility, reducing its bioavailability.

Targeted delivery of the metastasis-specific tumour homing TMTP1 peptide to non-small-cell lung cancer (NSCLC) using inhalable hybrid nano-assemblies.

Lung cancer is one of the most fatal malignancies, with the highest death rate (∼19%), and the NSCLC type accounts for ∼85% of lung cancers. In the search for new treatments, antimicrobial peptides have received much attention due to their propensity for selective destruction of cancer cells. In the current study, we evaluated the efficacy of the metastasis-specific tumour-homing-TMTP1 peptide against lung cancer using inhalable hybrid nano-assemblies of the PEG-PLGA copolymer as a carrier for pulmonary delivery which was assessed for aerodynamic and physicochemical properties, along with the peptide-release profile, physical stability, cellular uptake and biocompatibility, generation of reactive oxygen species, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells.

Strategic Developments in Polymer-Functionalized Liposomes for Targeted Colon Cancer Therapy: An Updated Review of Clinical Trial Data and Future Horizons.

Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges.

Effective cerebral tuberculosis treatment nose-to-brain transport of anti-TB drugs using mucoadhesive nano-aggregates.

Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB.

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression.

(Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix.

Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer's Disease.

Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer's disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD.

Self-actuating inflammation responsive hydrogel microsphere formulation for controlled drug release in rheumatoid arthritis (RA): Animal trials and study in human fibroblast like synoviocytes (hFLS) of RA patients.

Patients with rheumatoid arthritis (RA) often have one or more painfuljoints despite adequate medicine. Local drug delivery to the synovial cavity bids for high drug concentration with minimal systemic adverse effects. However, anti-RA drugs show short half-lives in inflamed joints after intra-articular delivery.

Recent Developments in Tyrosine Kinase Inhibitor-based Nanotherapeutics for EGFR-resistant Non-small Cell Lung Cancer.

The advent of drug resistance in response to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI) targeted therapy represents a serious challenge in the management of non-small cell lung cancer (NSCLC). These acquired resistance mutations, attributed to several advanced EGFR mutations and, necessitated the development of new-generation TKIs. Nanomedicine approaches provide a plausible way to address these problems by providing targeted delivery and sustained release, which have demonstrated success in preclinical trials.

Clofazimine nanoclusters show high efficacy in experimental TB with amelioration in paradoxical lung inflammation.

The rise of tuberculosis (TB) superbugs has impeded efforts to control this infectious ailment, and new treatment options are few. Paradoxical Inflammation (PI) is another major problem associated with current anti-TB therapy, which can complicate the treatment and leads to clinical worsening of disease despite a decrease in bacterial burden in the lungs. TB infection is generally accompanied by an intense local inflammatory response which may be critical to TB pathogenesis.

New Generation Smart Drug Delivery Systems for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most common form of the chronic inflammatory autoimmune disease characterized by chronic synovitis, synovial proliferation, and cellular infiltration. Further, it leads to bone erosion, destruction of articular cartilage, intense joint pain, swelling, and a high rate of disability, causing an immense load on human health. If the disease is identified early on, and the patient has continuous and timely treatment, many patients can achieve remission.

A wideband hybrid combiner design for ITER ion cyclotron radio frequency source.

The high-power radio frequency source for ion cyclotron heating and current drive of ITER tokamak consists of two identical 1.5 MW amplifier chains. These two chains will be combined using a wideband hybrid combiner with adequate coupling flatness, phase balance, return loss, and isolation response to generate 2.

Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials.

Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections.

Taming the Devil: Antimicrobial Peptides for Safer TB Therapeutics.

Tuberculosis (TB) is a highly contagious infection with extensive mortality and morbidity. The rise of TB-superbugs (drug-resistant strains) with the increase of their resistance to conventional antibiotics has prompted a further search for new anti-mycobacterial agents. It is difficult to breach the barriers around TB bacteria, including mycolic cell wall, granuloma, biofilm and mucus, by conventional antibiotics in a short span of time.

Efficient, enzyme responsive and tumor receptor targeting gelatin nanoparticles decorated with concanavalin-A for site-specific and controlled drug delivery for cancer therapy.

The tumor targeting and stimuli responsiveness behavior of intelligent drug delivery systems imparts effective therapeutic delivery and decreases the toxicity of conventional chemotherapeutic agents in off-target organs. To achieve the receptor targeting and smart drug release, several strategies have been employed to engineer nano-carrier with stimulus sensitivity. In this work, mannose receptor-targeted and matrix metalloproteinase (MMP) responsive gelatin nanoparticles were developed and assessed for its receptor targeting and "on-demand" controlled drug delivery in lung cancer therapeutics.

Development of an efficient antitick natural formulation for the control of acaricide-resistant ticks on livestock.

Animal production has a key role in global economic development and food security. Ticks, specifically Rhipicephalus microplus cause substantial economic and health impacts on more than eighty percent of the world cattle population. Though synthetic acaricides play a major role in tick management, their injudicious usage has caused environmental pollution and also promote the establishment of multi-acaricide resistant tick populations which is a matter of great concern.