Ibrutinib Loaded Nanostructured Lipid Carriers for the Management of Chronic Lymphocytic Leukemia: Synchronizing In Silico, In Vitro, and In Vivo Studies.

Introduction: Ibrutinib is a selective tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). However, it has low oral bioavailability (2.9%), which is attributed to low solubility (0.

Internal mechanism failure of magnetic controlled growing rods (MCGRs) for early-onset scoliosis: a systematic review of implant retrieval analysis studies.

Purpose: Magnetic controlled growing rods (MCGRs) are used to treat early-onset scoliosis when nonsurgical options fail, controlling curve progression and allowing for continued spinal growth. Recent reports of unplanned reoperations and mechanical failure of MCGRs have led to further research. This is a systematic review on the retrieval analysis of explanted MCGR rods.

Hybrid Principles of RGB12 and QbD To Photoinduced Electron Transfer Mechanism Based Sensitive and Green Nano-scale Spectrofluorimetric Insights for Estimation of Brucine.

This study proposes a sensitive and green spectrofluorimetric method for assessing brucine in solid dispersion adsorbate formulations and spiked plasma samples by combining quality by design principles with white analytical chemistry concepts. This method attains nanogram-level sensitivity by employing fluorescein as a biosensing probe through photoinduced electron transfer. The targeted formulation showed improved solubility and dissolution rates compared with those of pure brucine.

Optimization of IRAK1/4/pan-FLT3 kinase inhibitors as treatments for acute myeloid leukemia.

FLT3 kinase inhibitors have been advanced to the clinic as targeted treatments for acute myeloid leukemia (AML). These inhibitors can produce promising initial responses, but patients often relapse with treatment-resistant disease. A significant factor contributing to relapse involves adaptive signaling through an alternative pathway mediated by IRAK1 and IRAK4 kinases.

Immunoglobulin A-Dominant Post-Infectious Glomerulonephritis Mimicking Henoch-Schönlein Purpura Nephritis in a Patient With Methicillin-Sensitive Staphylococcus aureus Bacteremia.

Staphylococcal infections remain a prominent cause of hospital- and community-acquired infections in the United States. Glomerulonephritis with predominant Immunoglobulin A (IgA) deposition following staphylococcal infection has been described as IgA-dominant postinfectious glomerulonephritis (IgA-PIGN). This clinical entity can mimic Henoch-Schönlein purpura nephritis (HSPN) given that it may also be preceded by staphylococcal infection, have similar kidney biopsy findings, and present with similar signs and symptoms.

Design and Preliminary In vitro Investigation on Core Shell Nanoparticles Laden In Situ Gel for Corneal Neovascularization.

Background: The inherent limitation of ocular dosage forms is decreased precorneal residence time which affects the bioavailability and therapeutic efficacy.

Objective: The objective of the current research was to sustain drug release and enhance precorneal drug residence time by formulating lipidic core-shell nanoparticles of Dexamethasone Sodium Phosphate and loading them in ion-sensitive in situ gel for corneal neovascularization.

Methods: Polymeric nanoparticles were formulated using Eudragit L100-55 and PVA by twostep solvent diffusión nanoprecipitation method and coated by a lipidic film of Soya phosphatidylcholine with Cholesterol.

Transformation of a Potent C9-Substituted Phenylmorphan into MOR Partial Agonists with Improvement of Metabolic Stability: An In Vitro, In Vivo, and In Silico Study.

Replacement of the phenolic hydroxy in 3-((1,5,9)-2-phenethyl-9-vinyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol (), a potent efficacious MOR agonist, with an amide bioisosteric moiety provided a MOR partial agonist with morphine-like potency in the forskolin-induced cAMP accumulation assay and in the [S]GTPγS functional assay.

Operative management of congenital early-onset scoliosis using the vertical expandable prosthetic titanium rib (VEPTR): a case series.

To analyze surgical challenges and outcomes in patients who completed the whole journey of vertical expandable prosthetic titanium rib (VEPTR) treatment for congenital early-onset scoliosis (C-EOS), given the limited evidence available on VEPTR graduates. A retrospective review was conducted on nine consecutive patients with C-EOS and thoracic hypoplasia treated at a single tertiary care center, with assessment of clinical and radiological outcomes. At mean duration of 7.

IRAK1/4/pan-FLT3 Kinase Inhibitors with Reduced hERG Block as Treatments for Acute Myeloid Leukemia.

We report the optimization of a series of IRAK1/4/pan-FLT3 kinase inhibitors. These efforts have produced a key compound that displays potent and selective inhibition of IRAK1, IRAK4, and FLT3, reduced block of hERG, and good pharmacokinetic properties. In a mouse xenograft model of acute myeloid leukemia (AML), produces survival prolongation superior to that of gilteritinib, the leading FDA-approved FLT3 inhibitor currently used to treat AML.

Integration of Synchronizing In Silico, In Vitro, and In Vivo Strategies for the Development of Antipsoriatic Apremilast-loaded Nanostructured Lipid Carrier Embedded in Hydrogel.

One of the major challenges in the psoriasis therapies is the systemic side effects. This research investigation intended to design, formulate, and characterize topical Apremilast (APR) nanostructured lipid carriers (NLCs) embedded hydrogel. APR-loaded NLCs were prepared using the hot melt ultrasonication technique using glyceryl monostearate (GMS) and Capmul MCM, followed by high-speed homogenization.

Minimally Invasive Posterior Plating for Comminuted Middle to Distal One-Third Humeral Shaft Fractures: A Case Report.

Introduction: Humeral shaft fractures constitute 1-1.5% of all fractures, with most occurring in the middle and distal segments. While conservative treatment is common, surgical fixation is often preferred for displaced or comminuted fractures, particularly in young, active individuals.

Investigating blood-brain barrier penetration and neurotoxicity of natural products for central nervous system drug development.

Natural Products (NPs) are increasingly utilized worldwide for their potential therapeutic benefits, including central nervous system (CNS) disorders. Studies have shown açai berries mitigating Parkinson's disease progression through dopaminergic neuroprotection via Nrf-2 HO-1 pathways. Ashwagandha, an evergreen shrub, has shown potential as a therapeutic for neurodegenerative disorders via axonal regeneration in Aβ25-35-treated cortical neurons in vitro.

, , and studies of celecoxib topical platforms for antimicrobial activity and wound healing: a comparative assessment.

Background & Rationale: Celecoxib (CXB), with its anti-inflammatory and recently discovered antibacterial activity, especially against sensitive and methicillin-resistant could be promising in treating local pain, superficial skin infections, wounds and infected wounds. The study aims to develop and compare commercially scalable topical formulations of CXB to explore their antimicrobial and wound-healing potential.

Methods: Carbopol gel, o/w cream, polyethylene glycol (PEG) ointment, and paraffin ointment were selected as the vehicles for the preparation of 3% CXB topical formulations.

TomoCPT: a generalizable model for 3D particle detection and localization in cryo-electron tomograms.

Cryo-electron tomography is a rapidly developing field for studying macromolecular complexes in their native environments and has the potential to revolutionize our understanding of protein function. However, fast and accurate identification of particles in cryo-tomograms is challenging and represents a significant bottleneck in downstream processes such as subtomogram averaging. Here, we present tomoCPT (Tomogram Centroid Prediction Tool), a transformer-based solution that reformulates particle detection as a centroid-prediction task using Gaussian labels.

In-vivo microwave-aided spectrofluorimetric characterization of teneligliptin-loaded solid dispersion adsorbate using quality by design approach.

This study developed a microwave-aided spectrofluorimetric method for in-vivo characterizing teneligliptin-loaded solid dispersion adsorbate (TNG-SDA) using a quality by design approach. The microwave-aided chemical reaction was applied for derivatization of non-fluorescent teneligliptin with NBD-Cl (7-chloro-4-nitrobenzoxadiazole). TNG-SDA was prepared to enhance the solubility and bioavailability of teneligliptin, a BCS (Biopharmaceutical Classification System) class II drug.

Discovery of IRAK1/4/pan-FLT3 Kinase Inhibitors as Treatments for Acute Myeloid Leukemia.

We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.

Developing Robust Human Liver Microsomal Stability Prediction Models: Leveraging Inter-Species Correlation with Rat Data.

Pharmacokinetic issues were the leading cause of drug attrition, accounting for approximately 40% of all cases before the turn of the century. To this end, several high-throughput in vitro assays like microsomal stability have been developed to evaluate the pharmacokinetic profiles of compounds in the early stages of drug discovery. At NCATS, a single-point rat liver microsomal (RLM) stability assay is used as a Tier I assay, while human liver microsomal (HLM) stability is employed as a Tier II assay.

Investigation of Mirabegron-loaded Nanostructured Lipid Carriers for Improved Bioabsorption: Formulation, Statistical Optimization, and In-Vivo Evaluation.

Overactive bladder (OAB) is a usual medical syndrome that affects the bladder, and Mirabegron (MBG) is preferred medicine for its control. Currently, available marketed formulations (MYRBETRIQ® granules and MYRBETRIQ® ER tablets) suffer from low bioavailability (29-35%) hampering their therapeutic effectiveness and compromising patient compliance. By creating MBG nanostructured lipid carriers (MBG-NLCs) for improved systemic availability and drug release, specifically in oral administration of OAB treatment, this study aimed to address these issues.

PLGA Nanoparticles Based Mucoadhesive Nasal In Situ Gel for Enhanced Brain Delivery of Topiramate.

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M.

Amidino-rocaglates (ADRs), a class of synthetic rocaglates, are potent inhibitors of SARS-CoV-2 replication through inhibition of viral protein synthesis.

Coronaviruses are highly transmissible respiratory viruses that cause symptoms ranging from mild congestion to severe respiratory distress. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the need for new antivirals with broad-acting mechanisms to combat increasing emergence of new variants. Currently, there are only a few antivirals approved for treatment of SARS-CoV-2.

Discerning computational, in vitro and in vivo investigations of self-assembling empagliflozin polymeric micelles in type-2 diabetes.

Background: Empagliflozin (EMPA) is an SGLT2 inhibitor, a new class of anti-diabetic medication, indicated for treating type-2 diabetes. Its low permeability, poor solubility and bioavailability limits its use in management of diabetes. The study was aimed to formulate EMPA loaded polymeric micelles (PMs) to overcome these obstacles in oral absorption.

Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing.

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach.

In-vivo pharmacokinetic study of ibrutinib-loaded nanostructured lipid carriers in rat plasma by sensitive spectrofluorimetric method using harmonized approach of quality by design and white analytical chemistry.

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles.