Molecular dynamics in pharmaceutical nanotechnology: simulating interactions and advancing applications.

Molecular Dynamics (MD) simulations are now widely utilized in pharmaceutical nanotechnology to gain deeper understanding of nanoscale processes imperative to drug design. This review has also detailed how MD simulation can be employed in the study of drug-nanocarrier interactions, controlling release of chemical compounds from drug delivery systems and increasing solubility and bioavailability of nanocarriers. Furthermore, MD contributes to examining the drug delivery systems, measuring the toxic effects, and determining biocompatibility of nanomedical systems.

From challenges to solutions: A review of fourth-generation EGFR tyrosine kinase inhibitors to overcome the C797S triple mutation in non-small cell lung cancer.

This Review discusses recent advancements in the development of fourth-generation "Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs)" targeting resistance mutations, with an emphasis on the C797S mutation in "Non-small Cell Lung Cancer (NSCLC)". While first, second, and third-generation EGFR-TKIs have made significant progress in overcoming EGFR kinase resistance, the emergence of the EGFR-C797S mutation poses a substantial challenge, particularly in the context of resistance to Osimertinib. Fourth-generation TKIs are classified into ATP-competitive, allosteric, and ortho-allosteric inhibitors, with the goal of enhancing specificity for mutant EGFR while minimizing off-target effects on wild-type EGFR to reduce toxicity.

Orthoallosteric EGFR-TKIs: A New Paradigm in NSCLC Treatment Strategy Targeting the C797S Mutation.

The remarkable clinical success of third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has significantly advanced the treatment landscape for non-small-cell lung cancer (NSCLC). However, the emergence of the tertiary point mutation C797S poses a substantial obstacle to their clinical efficacy, leading to a dearth of FDA-approved targeted therapies for patients harboring this mutation. Addressing this pressing clinical challenge necessitates the development of novel therapeutic agents targeting the clinically challenging EGFR mutation.

Design, Synthesis, and Evaluation of Novel 2,4-disubstituted Pyrimidine Derivatives as Double Mutant Epidermal Growth Factor Receptor-L858R/T790M Tyrosine Kinase Inhibitors.

A series of 2,4-disubstituted pyrimidine derivatives bearing 5-substituted-1,3,4 thidiazole were devised and synthesized based on the binding mode of the approved drug Osimertinib with the ATP competitive site of EGFR-L858R/T790M in order to increase selectivity towards double mutant EGFR and potent antitumor activity. Their cellular bioactivity and corresponding enzyme inhibition were studied, and it was revealed that several compounds had significant biological activity and selectivity when compared to the control compounds. One of the most promising compound 8, substantially suppressed the proliferation of H1975 cells and showed significant inhibition of double mutant EGFR-L858R/T790M TK with IC values of 0.

ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP-IV, α-amylase, and α-glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential.

The study investigates the inhibitory properties of Mangiferin and Friedelin against glucokinase, DPP-IV, α-amylase, and α-glucosidase using computational methods, in vitro enzyme assays, and in-depth ADMET analysis. The study utilized a computer-aided drug design approach to assess the potential therapeutic properties of Mangiferin and Friedelin as T2DM therapeutic agents. Molecular docking studies' outcomes encouraged the evaluation of both compounds in in vitro enzymatic assays.

Catalytic Lysine745 targeting strategy in fourth-generation EGFR tyrosine kinase inhibitors to address C797S mutation resistance.

Overcoming resistance to third-generation tyrosine kinase inhibitors (TKIs) such as Osimertinib, particularly due to the emergence of the C797S mutation, remains a key challenge in non-small cell lung cancer (NSCLC) therapy. This review highlights recent advancements in the development of fourth-generation EGFR inhibitors that specifically target the catalytic Lys745 residue, aiming to overcome resistance associated with Osimertinib. Both covalent and non-covalent inhibitors targeting Lys745 were explored, using warheads like sulfonyl fluoride, phosphine oxides, esters, and trisubstituted imidazoles.

QbD-guided phospholipid-tagged nanonized boswellic acid naturosomal delivery for effective rheumatoid arthritis treatment.

Studies have reported the potential role of Boswellic acids (BAs), bioactive pentacyclic triterpenes from (BS), in treating rheumatoid arthritis (RA). However, poor water solubility and limited oral absorption are restricting factors for its better therapeutic efficacy. Based on these assumptions, the current study aimed to develop naturosomal delivery of BAs to boost their extremely low bioavailability, colloidal stability, and water solubility.

Nano-enabled pharmacogenomics: revolutionizing personalized drug therapy.

The combination of pharmacogenomics and nanotechnology science of pharmacogenomics into a highly advanced single entity has given birth to personalized medicine known as nano-enabled pharmacogenomics. This review article covers all aspects starting from pharmacogenomics to gene editing tools, how these have evolved or are likely to be evolved for pharmacogenomic application, and how these can be delivered using nanoparticle delivery systems. In this prior work, we explore the evolution of pharmacogenomics over the years, as well as new achievements in the field of genomic sciences, the challenges in drug creation, and application of the strategy of personalized medicine.

Extension of impurity profiling on eltrombopag olamine to in-silico predictions: An effort to exploit correlated forced degradation products and known drug-related substances in drug discovery.

The recent pandemic has highlighted the impact of diseases on global health and the economy. The rapid discovery of new hit molecules remains a tough challenge. Pharmaceutical impurity profiling can be linked to drug discovery through the identification of new hits from compounds identified during the analytical profiling.

Montmorillonite: An advanced material with diverse pharmaceutical and medicinal applications.

Montmorillonite (MMT) clay is composed of naturally layered silicate. The clays were more popular in the pharmaceutical and other various fields due to their beneficial physicochemical properties viz. non-toxicity, high surface area, efficient adsorption capability, high swellability, high dispersibility, thixotropic behaviour, and cation exchange capacity.

Nanoengineered Platform-Based Microenvironment-Triggered Immunotherapy in Cancer Treatment.

The immune system and cancer cells interact intricately during the growth of tumors, and the dynamic interplay between immune activation and suppression greatly influences the cancer outcome. Natural killer cells (NK), cytotoxic T lymphocytes (CTLs) and Dendritic cells (DC), employ diverse mechanisms, to combat cancer. However, the challenges posed by factors such as chronic inflammation and the immunosuppressive tumor microenvironment (TME) often hinder immune cells' ability to detect and eliminate tumors accurately.

An investigative review for pharmaceutical analysis of angiotensin receptor blockers: Olmesartan medoxomil.

Hypertension is often asymptomatic and can substantially elevate the risk of cardiovascular complications. Olmesartan medoxomil works by competitively blocking the angiotensin II receptors, preventing angiotensin II from constructing the blood vessels and releasing aldosterone. This discussion is focused on the critical analytical methods used to analyze olmesartan medoxomil in pharmaceutical and biological samples.

Eco-friendly hydrotropic spectrophotometric analysis of ranolazine hydrochloride.

Simple and eco-friendly biodegradable hydrotropes-assisted spectrophotometric experiments have been designed and validated to quantify ranolazine hydrochloride (RAN.HCl) in extended-release tablets. The citric acid and sodium citrate are employed as hydrotropes, serving as promising alternatives to polar organic solvents.

Inhibition of monoamine oxidases and neuroprotective effects: chalcones vs. chromones.

Eighteen compounds derived from two sub-series, (HC1-HC9) and (HF1-HF9), were synthesized and evaluated for their inhibitory activities against monoamine oxidase (MAO). HC (chalcone) series showed higher inhibitory activity against MAO-B than against MAO-A, whereas the HF (chromone) series showed reversed inhibitory activity. Compound HC4 most potently inhibited MAO-B with an IC value of 0.

Synthesis, optical properties, DNA, β-cyclodextrin interactions, and antioxidant evaluation of novel isoxazolidine derivative (ISoXD2): A multispectral and computational analysis.

are well explored among versatile and outstanding class of pharmacophores for the preparation and discovery of drugs. Herein, the electronic absorption and emission spectra of were investigated in three different solvents. The observed transition was attributed to π-π* with charge transfer character.

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

Background: Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures.

Design of Optimized Solid Lipid Nanoparticles of Montelukast Sodium and Assessment of Oral Bioavailability in Experimental Model.

Introduction: The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs.

Method: The study encompasses a 23 full factorial statistical design approach where mean particle size (Y1) and percent entrapment efficiency (Y2) were screened as dependent variables while, the concentration of lipid (X1), surfactant (X2), and co-surfactant (X3) were screened as independent variables.

Solidification of deep eutectic solvent containing fimasartan through wet impregnation and exploration of flow attributes by modified SeDeM-SLA expert system.

The solidification of deep eutectic solvent (DES) through wet impregnation techniques on inert solid carriers is an interesting approach that offers better processing attributes and excellent stability. Herein, DES of Fimasartan (FS) was developed to improve its solubility and bioavailability. The selected DES-FS was solidified by wet impregnation method employing Nesulin US2 and Aerosil 200.

Exploring the structural activity relationship of the Osimertinib: A covalent inhibitor of double mutant EGFR tyrosine kinase for the treatment of Non-Small Cell Lung Cancer (NSCLC).

The USFDA granted regular approval to Osimertinib (AZD9291) on March 2017, for treating individuals with metastatic Non-Small Cell Lung Cancer having EGFR T790M mutation. Clinically, Osimertinib stands at the forefront for the treatment of patients with Non-Small Cell Lung Cancer. Osimertinib forms a covalent bond with the Cys797 residue and predominantly spares binding to WT-EGFR, thereby reducing toxicity and enabling the administration of doses that effectively inhibit T790M.