Bio and NanoMaterials Lab, Drug Delivery and Controlled Release, Universidad de Talca, Talca, Maule, Chile; Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Maule, Chile.
Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Maule, Chile.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112483. doi: 10.1016/j.msec.2021.112483. Epub 2021 Oct 13.
A rational design accurate based on the use of Statistical Design of the Experiments (DoE) and Molecular Dynamics Simulations Studies allows the prediction and the understanding of thermo-responsive hydrogels prepared regarding their gelation temperature and anti-cancer drug release rate. N-isopropylacrilamide (NIPAM) modified with specific co-monomers and crosslinkers, can be used to prepare "on-demand" thermo-responsive hydrogels with the ideal properties for clinical applications in which local sustained release of drugs is crucial. Two preferential formulations resulting from the predictive studies of DoE and In Silico methods were synthesized by radical polymerization, fully characterized, and loaded with the anticancer drug Doxorubicin (Dox). The hydrogel formulations were characterized by swelling rate, turbidity, FTIR, H NMR, SEM, gelation time, rheology, and biocompatibility assays. Both formulations demonstrated adequate morphologic, rheological, and biocompatibility properties; however, important differences in terms of drug retention were detected. As demonstrated by a Dox cumulative release study and posteriorly confirmed by an efficacy assay in an in vitro colorectal cancer model, the formulation composed by NIPAM and 4-penten-1-ol crosslinked with poly(ethylene glycol) diacrylate (PEGDA) (PNiPenPH) present a slow release over the time, presenting ideal properties to become and ideal depot system for the local sustained release of anticancer drugs as adjuvant therapy or in the case of non-resectable tumors.
基于统计实验设计（DoE）和分子动力学模拟研究的合理设计，可以预测和理解针对其胶凝温度和抗癌药物释放率制备的热响应水凝胶。用特定的共聚单体和交联剂改性的 N-异丙基丙烯酰胺（NIPAM）可用于制备“按需”热响应水凝胶，这些水凝胶具有理想的临床应用特性，对于局部持续释放药物至关重要。两种优先配方是通过 DoE 和计算方法的预测研究合成的，通过自由基聚合进行了完全表征，并负载了抗癌药物阿霉素（Dox）。通过溶胀率、浊度、FTIR、H NMR、SEM、凝胶时间、流变学和生物相容性试验对水凝胶配方进行了表征。两种配方均表现出良好的形态、流变学和生物相容性特性；然而，在药物保留方面存在重要差异。正如 Dox 累积释放研究所示，随后在体外结直肠癌细胞模型中的功效试验中得到证实，由 NIPAM 和 4-戊烯-1-醇与聚乙二醇二丙烯酸酯（PEGDA）交联组成的配方（PNiPenPH）随着时间的推移呈现出缓慢释放，具有成为局部持续释放抗癌药物的理想储库系统的理想特性，可作为辅助治疗或在不可切除肿瘤的情况下使用。
