Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy.

Cardiotoxicity, especially human ether-a-go-go-related gene (hERG)-related toxicity, is a leading cause of drug failure or market withdrawal. Reducing hERG binding to obviate potential cardiac toxicity is crucial. Nanotechnology has been applied to drug delivery for reducing drug toxicity and improving efficacy, but few studies have addressed hERG-related cardiotoxicity.

Amphiphilic dendrimer-assisted delivery of antisense nucleic acid mimics against E. coli.

The rise in antimicrobial resistance and the consequent ineffectiveness of conventional antibiotics emphasise the need for novel therapeutic strategies. Antisense nucleic acid mimics (NAMs) are emerging as promising precision therapeutic agents, inhibiting specific genes through hybridisation with selected nucleic acid targets. However, delivering NAMs into bacteria remains a significant challenge.

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate.

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer , composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant and exhibited effective activity against drug-resistant bacterial infections in vivo.

Amphiphilic Dendrimer as Potent Antibacterial against Drug-Resistant Bacteria in Mouse Models of Human Infectious Diseases.

Modern medicine continues to struggle against antibiotic-resistant bacterial pathogens. Among the pathogens of critical concerns are the multidrug-resistant (MDR) , and . These pathogens are major causes of nosocomial infections among immunocompromised individuals, involving major organs such as lung, skin, spleen, kidney, liver, and bloodstream.

Promise of dostarlimab in cancer therapy: Advancements and cross-talk considerations.

In recent years, immunotherapy for cancer treatment using monoclonal antibodies has shown clinical success, particularly with programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Dostarlimab, an immune checkpoint inhibitor, interacts with adaptive immunity by binding to human PD-1, inhibiting PD-L1 and PD-L2 interactions, and cross-talk with adaptive immunity. Recent clinical trials have shown that dostarlimab is effective in treating mismatch repair deficiency (dMMR) in endometrial cancer patients, leading to its approval in the United States and the European Union in 2021.

Amphiphilic dendrimers against antibiotic resistance: light at the end of the tunnel?

With the alarming and prevailing antimicrobial resistance (AMR) comes an urgent need for novel antimicrobial agents that are not only effective and robust but also do not induce resistance development. Amphiphilic dendrimers are emerging as a promising new paradigm to combat bacterial AMR. They can mimic antimicrobial peptides to produce potent antibacterial activity yet with a low likelihood of generating resistance.

Bola-Amphiphilic Glycodendrimers: New Carbohydrate-Mimicking Scaffolds to Target Carbohydrate-Binding Proteins.

Dendrimers are appealing scaffolds for creating carbohydrate mimics with unique multivalent cooperativity. We report here novel bola-amphiphilic glycodendrimers bearing mannose and glucose terminals, and a hydrophobic thioacetal core responsive to reactive oxygen species. The peculiar bola-amphiphilic feature enabled stronger binding to lectin compared to conventional amphiphiles.

Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms.

The alarming and prevailing antibiotic resistance crisis urgently calls for innovative "outside of the box" antibacterial agents, which can differ substantially from conventional antibiotics. In this context, we have established antibacterial candidates based on dynamic supramolecular dendrimer nanosystems self-assembled with amphiphilic dendrimers composed of a long hydrophobic alkyl chain and a small hydrophilic poly(amidoamine) dendron bearing distinct terminal functionalities. Remarkably, the amphiphilic dendrimer with amine terminals exhibited strong antibacterial activity against both Gram-positive and Gram-negative as well as drug-resistant bacteria, and prevented biofilm formation.

Experimentally Validated QSAR Model for Surface p Prediction of Heterolipids Having Potential as Delivery Materials for Nucleic Acid Therapeutics.

The application of lipid-based drug delivery technologies for bioavailability enhancement of drugs has led to many successful products in the market for clinical use. Recent studies on amine-containing heterolipid-based synthetic vectors for delivery of siRNA have witnessed the United States Food and Drug Administration (USFDA) approval of the first siRNA drug in the year 2018. The studies on various synthetic lipids investigated for delivery of such nucleic acid therapeutics have revealed that the surface p of the constructed nanoparticles plays an important role.

Pharmaceutical analysis combined with in-silico therapeutic and toxicological profiling on zileuton and its impurities to assist in modern drug discovery.

The obligatory testing of drug molecules and their impurities to protect users against toxic compounds seems to provide interesting opportunities for new drug discovery. Impurities, which proved to be non-toxic, may be explored for their own therapeutic potential and thus be a part of future drug discovery. The essential role of pharmaceutical analysis can thus be extended to achieve this purpose.

Antimicrobial cell penetrating peptides with bacterial cell specificity: pharmacophore modelling, quantitative structure activity relationship and molecular dynamics simulation.

Current research has shown cell-penetrating peptides and antimicrobial peptides (AMPs) as probable vectors for use in drug delivery and as novel antibiotics. It has been reported that the higher the therapeutic index (TI) the higher would be the bacterial cell penetrating ability. To the best of our knowledge, no in-silico study has been performed to determine bacterial cell specificity of the antimicrobial cell penetrating peptides (aCPP's) based on their TI.

Self-microemulsifying drug delivery system for camptothecin using new bicephalous heterolipid with tertiary-amine as branching element.

Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity but its clinical use is limited due to its poor water solubility, stability at physiological conditions and toxicity. The aim of our study was to evaluate bicephalous heterolipid E1E for enhancing the solubility and stability of CPT through the development of a self-microemulsifying drug delivery system (SMEDDS). The solubility of CPT in heterolipid E1E was found to be 82 and 5.