Maleki Reza, Khedri Mohammad, Rezvantalab Sima, Beheshtizadeh Nima
Department of Chemical Technologies, Iranian Research Organization for Science and Technology (IROST), P.O. Box 33535111, Tehran, Iran.
Department of Chemical Engineering, Amirkabir University of Technology, 424 Hafez Avenue, Tehran, Iran.
J Biol Eng. 2024 Sep 9;18(1):49. doi: 10.1186/s13036-024-00445-0.
Before embarking on any experimental research endeavor, it is advisable to do a mathematical computation and thoroughly examine the methodology. Despite the use of polymeric nanocarriers, the regulation of bioavailability and drug release at the disease site remains insufficient. Several effective methods have been devised to address this issue, including the creation of polymeric nanocarriers that can react to stimuli such as redox potential, temperature, pH, and light. The present study has been utilized all-atom molecular dynamics (AA-MD) and coarse-grained molecular dynamics (CG-MD) methods and illustrated the drug release mechanism, which is influenced by pH, for Chitosan-Eudragit bioresponsive nanocarriers. The aim of current work is to study the molecular mechanism and atomistic interactions of PAX delivery using a Chitosan-Eudragit carrier. The ability of Eudragit polymers to dissolve in various organic solvents employed in the process of solvent evaporation is a crucial benefit in enhancing the solubility of pharmaceuticals. This study investigated the use of Chitosan-Eudragit nanocarriers for delivering an anti-tumor drug, namely Paclitaxel (PAX). Upon analyzing several significant factors affecting the stability of the drug and nanocarrier, it has been shown that the level of stability is more significant in the neutral state than the acidic state. Furthermore, the system exhibits higher stability in the neutral state. The used Chitosan-Eudragit nanocarriers exhibit a stable structure under alkaline conditions, but undergo deformation and release their payloads under acidic conditions. It was demonstrated that the in silico analysis of anti-tumor drugs and carriers' integration could be quantified and validated by experimental results (from previous works) at an acceptable level.
在开展任何实验研究工作之前，进行数学计算并全面审视方法是明智之举。尽管使用了聚合物纳米载体，但在疾病部位对生物利用度和药物释放的调控仍显不足。已经设计出了几种有效方法来解决这个问题，包括创建能够对氧化还原电位、温度、pH值和光等刺激做出反应的聚合物纳米载体。本研究利用全原子分子动力学（AA-MD）和粗粒度分子动力学（CG-MD）方法，阐明了壳聚糖-尤特奇生物响应性纳米载体受pH值影响的药物释放机制。当前工作的目的是研究使用壳聚糖-尤特奇载体递送紫杉醇（PAX）的分子机制和原子间相互作用。尤特奇聚合物在溶剂蒸发过程中能溶解于各种有机溶剂的能力，是提高药物溶解度的一个关键优势。本研究考察了壳聚糖-尤特奇纳米载体用于递送抗肿瘤药物紫杉醇（PAX）的情况。在分析了影响药物和纳米载体稳定性的几个重要因素后发现，在中性状态下的稳定性水平比酸性状态下更显著。此外，该系统在中性状态下表现出更高的稳定性。所使用的壳聚糖-尤特奇纳米载体在碱性条件下呈现稳定结构，但在酸性条件下会发生变形并释放其负载物。结果表明，抗肿瘤药物与载体整合的计算机模拟分析能够在可接受的水平上通过（来自先前工作的）实验结果进行量化和验证。
