A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone

Abstract

The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG2k; Mw = 2000 g mol−1) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations.

Design, Synthesis, and Characterization of Novel Series of Pharmacologically-important Sperm-shaped Amphiphilic Heterocyclic Compounds derived from Natural Palmitic Acid

“…of all the four newly-synthesized compounds 2a-2d were perfectly compliant with the targeted chemical structures. In this model of amphiphilic structure (Figure 3), we can make use of this cocktail or hybrid pharmacophore in many different ways in pharmceutical and medicinal chemistry (Gao et al, 2021;Jubie et al, 2012;Mittal et al, 2021;Mushtaq et al, 2021;Rabie, 2021b). First, pharmacokinetically, if we want to design certain drugs that have all the three main states of gradual polarity (polar, semipolar, and nonpolar) to effectively be distributed and pass through the diverse biological liquids and membranes, hundreds of compounds can be easily synthesized based on this backbone.…”

A novel link between chronic inflammation and humanin regulation in children

“…Therefore, new treatment strategies are highly desired to prevent bone growth impairment caused by chronic inflammation. Moreover, glucocorticoids (GCs) are also widely used in the management of IBD and several attempts have been made to reduce the toxicity of GCs ( 35 – 37 ). Interestingly, it has been reported that the combination of the humanin analog HNG with a GC does not interfere with the desired anti-inflammatory effects of the GC ( 12 , 38 ).…”

Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application

“…In this respect, synthetic amphiphilic block copolymers are promising systems. , Amphiphilic block copolymers consist of two or more blocks with various chemical groups. They form highly organized systems, which can be excipients for molecules of drugs.. , Pluronics are among the most widely used block copolymers. A block copolymer Pluronic P123 is a well-known pharmaceutical excipient.…”