A Mechanistic Insight into Doxorubicin Adsorption on N-isopropyl Acrylamide Grafted Nanotube: Optimization Study of Loading Temperature

Abstract

Background: The drug development process is costly and time-consuming; hence, nowadays, enormous efforts have been established through computational studies for finding appropriate strategies, methods and solutions for enhancing the drug production and administration procedures. Hydrogels that undertake deformation upon pertinent changes in temperature have significant aptitude as drug delivery systems. These biomaterials have made a substantial impact on the development of drugs for critical diseases, especially cancer therapy. Drug loading and uptake are primary and fundamental steps of the drug development and discovery process. N-isopropyl acrylamide is a common and well-known thermo-sensitive and injectable hydrogel for the drug uptake under the lower critical solution temperature (LCST). In the current study, carbon nanotube (CNT) as a nanocarrier was modified via N-isopropyl acrylamide. On the other hand, Doxorubicin as an anti-cancer drug applied on mentionted systems to develop drug packing at three different temperatures. Results: After computational parametrization of the system via bioinformatics software and databases, Molecular dynamics (MD) simulation was run. To this end, the detailed simulations were carried out to reveal the interaction energy, numbers of hydrogen bonds, the gyration radius, mean square displacement, and radial distribution function as well as Gibss free energy. Besides, the optimal loading temperature for doxorubicin was determined. The results achieved from simulating the polymer demonstrated a decrease in the gyration radius at a higher temperature. A decrease of gyration radius resulted in more concentrated aggregation with stronger bonds.Conclusions: Therefore, at the higher temperature, the more stable polymer interaction and better doxorubicin loading were acquired. The smart absorption of doxorubicin onto the CNT modified via N-iso-propyl acrylamide (NIPA) give a significant and valuable view on the future studies regarding the drug development and novel, biocompatible, and biodegradable stimuli-sensitive drug delivery system.