PEI-based functional materials: Fabrication techniques, properties, and biomedical applications.

Cationic polymers have recently attracted considerable interest as research breakthroughs for various industrial and biomedical applications. They are particularly interesting due to their highly positive charges, acceptable physicochemical properties, and ability to undergo further modifications, making them attractive candidates for biomedical applications. Polyethyleneimines (PEIs), as the most extensively utilized polymers, are one of the valuable and prominent classes of polycations. Owing to their flexible polymeric chains, broad molecular weight (MW) distribution, and repetitive structural units, their customization for functional composites is more feasible. The specific beneficial attributes of PEIs could be introduced by purposeful functionalization or modification, long service life, biocompatibility, and distinct geometry. Therefore, PEIs have significant potential in biotechnology, medicine, and bioscience. In this review, we present the advances in PEI-based nanomaterials, their transfection efficiency, and their toxicity over the past few years. Furthermore, the potential and suitability of PEIs for various applications are highlighted and discussed in detail. This review aims to inspire readers to investigate innovative approaches for the design and development of next-generation PEI-based nanomaterials possessing cutting-edge functionalities and appealing characteristics.

Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases.

The use of biomarkers as early warning systems in the evaluation of disease risk has increased markedly in the last decade. Biomarkers are indicators of typical biological processes, pathogenic processes, or pharmacological reactions to therapy. The application and identification of biomarkers in the medical and clinical fields have an enormous impact on society. In this review, we discuss the history, various definitions, classifications, characteristics, and discovery of biomarkers. Furthermore, the potential application of biomarkers in the diagnosis, prognosis, and treatment of various diseases over the last decade are reviewed. The present review aims to inspire readers to explore new avenues in biomarker research and development.

Enhancement of the brain delivery of methotrexate with administration of mid-chain ester prodrugs: In vitro and in vivo studies.

In the present study, with the aim of improving the permeability of methotrexate (MTX) to the brain, the lipophilic MTX prodrugs containing the ester functional moiety were synthesized. The chemical structure of synthesized prodrugs was characterized and confirmed by FT-IR, NMR and mass spectral studies. Based on the results of in vitro cytotoxic studies, all of the synthesized prodrugs led to decrease in the IC50 in 72 h on U87 cancer cell line and the best result was observed for dihexyl methotrexate (MTX-DH) in comparison with free MTX, which led to decrease the IC50 amount up to 6 folds. In addition, in vivo toxicity on Artemia salina (A. salina) showed that the lipophilic MTX prodrugs have been able to partially mask the toxic profile of free MTX, at the same concentrations. These findings were also in compliance with hemolysis assay results, which confirm that the conjugates has not made the drug more toxic. Furthermore, in vivo study in rat model, was employed to determine the simultaneous drug concentration in brain and plasma. According to the obtained results, the brain-to-plasma concentration ratios (Kp values) of MTX-DH and dioctyl methotrexate (MTX-DO) groups were significantly higher compared with free MTX. Moreover, the uptake clearance of MTX by brain parenchyma increased significantly (3.85 and 9.08-time increased for MTX-DH and MTX-DO prodrugs, respectively). These findings indicate that the synthesized lipophilic MTX prodrugs are non-toxic and able to enhance brain penetration of MTX.

In vitro immunobiological assays of methotrexate-stearic acid conjugate in human PBMCs.

In the present research, a lipophilic methotrexate (MTX) prodrug was developed by covalent conjugating of MTX to stearic acid (SA) as a lipid moiety via amid bond. The structure of synthesized conjugate, MTX-SA, was confirmed by IR and NMR spectra. To evaluate inflammatory response of MTX-SA conjugate and MTX, human PBMCs were isolated and exposed to 50, 500 and 5000 nM of MTX-SA conjugate and free MTX. The expression of four key genes involved in inflammation and apoptosis including IL-8, IL-1ß, IL-10 and Bcl2 depicted that the MTX-SA had controversial behavior in different doses on the inflammatory transcription. Also, MTX-SA statically decreased the number of immune live cells in comparison to MTX. However, MTX-SA did not capture PBMCs cell cycle in G0/G1 phase. Totally, these results showed MTX-SA with long lipid chain has different effect on immune responses and it is irrefutable that detailed studies of its immunotoxicity and immunogenicity ought to be taken into account.

Emerging insights on drug delivery by fatty acid mediated synthesis of lipophilic prodrugs as novel nanomedicines.

Many drug molecules that are currently in the market suffer from short half-life, poor absorption, low specificity, rapid degradation, and resistance development. The design and development of lipophilic prodrugs can provide numerous benefits to overcome these challenges. Fatty acids (FAs), which are lipophilic biomolecules constituted of essential components of the living cells, carry out many necessary functions required for the development of efficient prodrugs. Chemical conjugation of FAs to drug molecules may change their pharmacodynamics/pharmacokinetics in vivo and even their toxicity profile. Well-designed FA-based prodrugs can also present other benefits, such as improved oral bioavailability, promoted tumor targeting efficiency, controlled drug release, and enhanced cellular penetration, leading to improved therapeutic efficacy. In this review, we discuss diverse drug molecules conjugated to various unsaturated FAs. Furthermore, various drug-FA conjugates loaded into various nanostructure delivery systems, including liposomes, solid lipid nanoparticles, emulsions, nano-assemblies, micelles, and polymeric nanoparticles, are reviewed. The present review aims to inspire readers to explore new avenues in prodrug design based on the various FAs with or without nanostructured delivery systems.