Structural Deformation of MTX Induced by Nanodrug Conjugation Dictate Intracellular Drug Transport and Drug Efficacy
- Authors
- Park, Jun-Young; Hyun, Ja-Shil; Jee, Jun-Goo; Park, Sung Jean; Khang, Dongwoo
- Issue Date
- Jul-2021
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- structural deformation; methotrexate; covalent conjugation; rheumatoid arthritis; carbon nanotube
- Citation
- INTERNATIONAL JOURNAL OF NANOMEDICINE, v.16, pp.4943 - 4957
- Journal Title
- INTERNATIONAL JOURNAL OF NANOMEDICINE
- Volume
- 16
- Start Page
- 4943
- End Page
- 4957
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/81887
- DOI
- 10.2147/IJN.S317231
- ISSN
- 1176-9114
- Abstract
- Background: Understanding structural interactions between the active drug and conjugated nanoparticles is critical for optimizing intracellular drug transport and for increasing nano drug efficacy. In this regard, analyzing the conformational deformation of conjugated drugs surrounding nanoparticles is essential to understand the corresponding nanodrug efficacy. Purpose: The objective of this study is to present an optimal synthesis method for efficient drug delivery through a clear structural analysis of nanodrugs according to the type of conjugation. Methods and Results: In this study, the structural variation of methotrexate (MTX) surrounding carbon nanotubes, depending on the type of conjugation style, such as covalent and non-covalent (PEGylation) bonds, was investigated. Specifically, covalent bonds of MTX surrounding CNTs induced greater structural deformation compared to non-covalent bonds (ie, PEGylated CNT). Conclusion: Greater changes in the structural variations of MTX analyzed by nuclear magnetic resonance (NMR) significantly improved the anti-inflammatory drug efficacy of human fibroblast-like synovial cells (FLS) via stable drug release in the extracellular environment and burst drug release under intracellular conditions.
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