Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs.

Pulmonary administration of biodegradable polymeric formulation is beneficial in the treatment of various respiratory diseases. For respiratory delivery, the polymer must be non-toxic, biodegradable, biocompatible, and stable. Poly D, L-lactic-co-glycolic acid (PLGA) is a widely used polymer for inhalable formulations because of its attractive mechanical and processing characteristics which give great opportunities to pharmaceutical industries to formulate novel inhalable products. PLGA has many pharmaceutical applications and its biocompatible nature produces non-toxic degradation products. The degradation of PLGA takes place through the non-enzymatic hydrolytic breakdown of ester bonds to produce free lactic acid and glycolic acid. The biodegradation products of PLGA are eliminated in the form of carbon dioxide (CO2) and water (H2O) by the Krebs cycle. The biocompatible properties of PLGA are investigated in various in vivo and in vitro studies. The high structural integrity of PLGA particles provides better stability, excellent drug loading, and sustained drug release. This review provides detailed information about PLGA as an inhalable grade polymer, its synthesis, advantages, physicochemical properties, biodegradability, and biocompatible characteristics. The important formulation aspects that must be considered during the manufacturing of inhalable PLGA formulations and the toxicity of PLGA in the lungs are also discussed in this paper. Additionally, a thorough overview is given on the application of PLGA as a particulate carrier in the treatment of major respiratory diseases, such as cystic fibrosis, lung cancer, tuberculosis, asthma, and pulmonary hypertension.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

Molecular interaction analysis of ferulic acid (4-hydroxy-3-methoxycinnamic acid) as main bioactive compound from palm oil waste against MCF-7 receptors: An in silico study.

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phytochemical compound that is commonly found in conjugated forms within mono-, di-, polysaccharides and other organic compounds in cell walls of grain, fruits, and vegetables. This compound is highly abundant in the palm oil waste. The aim of the study was to predict the anticancer activity of ferulic acid against the breast cancer cell lines (MCF-7) receptors through a computational analysis. MCF-7 receptors with PDB IDs of 1R5K, 2IOG, 4IV2, 4IW6, 5DUE, 5T92, and 5U2B were selected based on the Simplified Molecular Input Line Entry System (SMILES) similarity of the native ligand. Thereafter, the protein was prepared on Chimera 1.16 and docked with ferulic acid on Autodock Vina 1.2.5. The ligand-protein complex interaction was validated by computing the root mean square fluctuation (RMSF) and radius of gyration (Rg) through molecular dynamic simulation. In addition, an absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was performed on ferulic acid using the pkCSM platform. The molecular docking revealed that the ferulic acid could interact with all receptors as indicated by the affinity energy <-5 kcal/mol. The compound had the most optimum interaction with receptor 2IOG (affinity energy=-6.96 kcal/mol), involving hydrophobic interaction (n=12) and polar hydrogen interaction (n=4). The molecular dynamic simulation revealed that the complex had an RMSF of 1.713 Å with a fluctuation of Rg value around 1.000 Å. The ADMET properties of ferulic acid suggested that the compound is an ideal drug candidate. In conclusion, this study suggested that ferulic acid, which can be isolated from palm oil waste, has the potential to interact with MCF-7 receptors.

A review of synthetic strategy, SAR, docking, simulation studies, and mechanism of action of isoxazole derivatives as anticancer agents.

Breast cancer (BC) is a global health concern and the leading cause of cancerous death among women across the world, BC has been characterized by fresh lump in the breast or underarm (armpit), thickened or swollen. Worldwide estimated 9.6 million deaths in 2018-2019. Numerous drugs have been approved by FDA for BC treatment but showed numerous adverse effects like bioavailability issues, selectivity issues, and toxicity issues. Therefore, there is an immediate need to develop new molecules that are non-toxic and more efficient for treating cancer. Isoxazole derivatives have gained popularity over the few years due to their effective antitumor potential. These derivatives work against cancer by inhibiting the thymidylate enzyme, inducing apoptosis, inhibiting tubulin polymerization, protein kinase inhibition, and aromatase inhibition. In this study, we have concentrated on the isoxazole derivative with structure-activity relationship study, various synthesis techniques, mechanism of action, docking, and simulation studies pertaining to BC receptors. Hence the development of isoxazole derivatives with improved therapeutic efficacy will inspire further progress in improving human health.Communicated by Ramaswamy H. Sarma.

Galangin as an inflammatory response modulator: An updated overview and therapeutic potential.

Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.

Application of CRISPR-Cas9 genome editing technology in various fields: A review.

CRISPR-Cas9 has emerged as a revolutionary tool that enables precise and efficient modifications of the genetic material. This review provides a comprehensive overview of CRISPR-Cas9 technology and its applications in genome editing. We begin by describing the fundamental principles of CRISPR-Cas9 technology, explaining how the system utilizes a single guide RNA (sgRNA) to direct the Cas9 nuclease to specific DNA sequences in the genome, resulting in targeted double-stranded breaks. In this review, we provide in-depth explorations of CRISPR-Cas9 technology and its applications in agriculture, medicine, environmental sciences, fisheries, nanotechnology, bioinformatics, and biotechnology. We also highlight its potential, ongoing research, and the ethical considerations and controversies surrounding its use. This review might contribute to the understanding of CRISPR-Cas9 technology and its implications in various fields, paving the way for future developments and responsible applications of this transformative technology.

Dry powder inhalers of antitubercular drugs.

Despite advancements in the medical and pharmaceutical fields, tuberculosis remains a major health problem globally. Patients do not widely accept the conventional approach to treating tuberculosis (TB) due to prolonged treatment periods with multiple high doses of drugs and associated side effects. A pulmonary route is a non-invasive approach to delivering drugs, hormones, nucleic acid, steroids, proteins, and peptides directly to the lungs, improving the efficacy of the treatment and consequently decreasing the adverse effect of the treatment. This route has been successfully developed for the treatment of various respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), tuberculosis (TB), lung cancer, and other pulmonary infections. The major approaches of inhalation delivery systems include nebulizers, metered-dose inhalers (MDIs), and dry powder inhalers (DPIs). However, dry powder inhalers (DPIs) are more advantageous due to their stability and ability to deliver a high dose of the drug to the lungs. The present review analyzes the modern therapeutic approach of inhaled dry powders, with a special focus on novel drug delivery system (NDDS) based DPIs for the treatment of TB. The article also discussed the challenges of preparing inhalable dry powder formulations for the treatment of TB. The clinical development of inhalable anti-TB drugs is also reviewed.