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

• Published in: Scientific reports 2021-11, Vol.11 (1), p.21507-14, Article 21507
• Main Authors: Mushtaq, Irrum, Akhter, Zareen, Farooq, Muhammad, Jabeen, Farukh, Rehman, Ashfaq Ur, Rehman, Sadia, Ayub, Sidra, Mirza, Bushra, Siddiq, Muhammad, Zaman, Farasat
• Format: Article
• Language: English
• Subjects: 639/638/298; 639/638/455; 639/638/898; Abscisic acid; Aniline; Anti-inflammatory agents; Antineoplastic Agents, Hormonal - chemistry; Antineoplastic Agents, Hormonal - pharmacology; Blood cells; Computer applications; Controlled release; Cytotoxicity; Dexamethasone; Dexamethasone - chemistry; Dexamethasone - pharmacology; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug Liberation; External stimuli; Hemolysis - drug effects; Humanities and Social Sciences; Humans; Hydrophobicity; Inflammation; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medicin och hälsovetenskap; Micelles; multidisciplinary; Oxidation; Polyethylene glycol; Polyethylene Glycols - chemistry; Polymers; Polymers - chemistry; Science; Science (multidisciplinary); Self-assembly; Spectroscopy; Steroids; Tumor Cells, Cultured
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-00871-w

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 (mPEG 2k ; M w  = 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.