A multiscale coarse-grained model to predict the molecular architecture and drug transport properties of modified chitosan hydrogels
A multiscale coarse-grained model to predict the molecular architecture and drug transport properties of modified chitosan hydrogels
复制标题
用于预测改性壳聚糖水凝胶的分子结构和药物转运特性的多尺度粗粒度模型
DOI：
10.1039/d0sm01243b
复制
发表时间：
2020
期刊：
影响因子：
3.4
通讯作者：
Grafmüller, Andrea
中科院分区：
文献类型：
--
作者：
Singhal, Ankush;Schneible, John D.;Lilova, Radina L.;Hall, Carol K.;Menegatti, Stefano;Grafmüller, Andrea
用官能化多糖构建的水凝胶在许多应用中是令人感兴趣的，主要是治疗和再生制剂的设计。调整多糖基水凝胶的化学改性以实现特定的药物释放性质涉及许多可调参数的优化，包括（i）官能团的类型、程度（X）和模式，（ii）水-聚合物比率，和（iii）药物有效载荷。为了指导用于药物释放的改性多糖水凝胶的设计，我们开发了一个计算工具箱，该工具箱预测酰化壳聚糖链的结构和物理化学性质，以及它们对药物分子转运的影响。在此，我们提出了一个多尺度粗粒度模型来研究乙酰基，丁酰基或庚酰基部分修饰的壳聚糖链的网络结构，以及药物阿霉素（Dox）和吉西他滨（Gem）通过所产生的网络的扩散。该模型预测形成不同的网络结构，特别是疏水驱动的过渡从一个统一的集群/通道形态和形成纤维的甲壳素链。该模型还描述了结构和物理化学性质对药物转运的影响，这是通过测量Dox和Gem扩散通过改性壳聚糖水凝胶的合奏实验证实。
Hydrogels constructed with functionalized polysaccharides are of interest in a multitude of applications, chiefly the design of therapeutic and regenerative formulations. Tailoring the chemical modification of polysaccharide-based hydrogels to achieve specific drug release properties involves the optimization of many tunable parameters, including (i) the type, degree (χ), and pattern of the functional groups, (ii) the water–polymer ratio, and (iii) the drug payload. To guide the design of modified polysaccharide hydrogels for drug release, we have developed a computational toolbox that predicts the structure and physicochemical properties of acylated chitosan chains, and their impact on the transport of drug molecules. Herein, we present a multiscale coarse-grained model to investigate the structure of networks of chitosan chains modified with acetyl, butanoyl, or heptanoyl moieties, as well as the diffusion of drugs doxorubicin (Dox) and gemcitabine (Gem) through the resulting networks. The model predicts the formation of different network structures, in particular the hydrophobically-driven transition from a uniform to a cluster/channel morphology and the formation of fibers of chitin chains. The model also describes the impact of structural and physicochemical properties on drug transport, which was confirmed experimentally by measuring Dox and Gem diffusion through an ensemble of modified chitosan hydrogels.