Soft Matter Chemistry, Department of Chemistry, Faculty of Science, University of Helsinki, A. I. Virtasen aukio 1, 00014 Helsinki, Finland.
Drug Research Program, Division of Pharmaceutical Biosciences Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014 Helsinki, Finland.
Mol Pharm. 2024 Jul 1;21(7):3356-3374. doi: 10.1021/acs.molpharmaceut.4c00086. Epub 2024 May 28.
Block copolymers, composed of poly(2-oxazoline)s and poly(2-oxazine)s, can serve as drug delivery systems; they form micelles that carry poorly water-soluble drugs. Many recent studies have investigated the effects of structural changes of the polymer and the hydrophobic cargo on drug loading. In this work, we combine these data to establish an extended formulation database. Different molecular properties and fingerprints are tested for their applicability to serve as formulation-specific mixture descriptors. A variety of classification and regression models are built for different descriptor subsets and thresholds of loading efficiency and loading capacity, with the best models achieving overall good statistics for both cross- and external validation (balanced accuracies of 0.8). Subsequently, important features are dissected for interpretation, and the DrugBank is screened for potential therapeutic use cases where these polymers could be used to develop novel formulations of hydrophobic drugs. The most promising models are provided as an open-source software tool for other researchers to test the applicability of these delivery systems for potential new drug candidates.
嵌段共聚物由聚（2-恶唑啉）和聚（2-恶嗪）组成，可以用作药物传递系统；它们形成胶束，携带水溶性差的药物。许多最近的研究调查了聚合物和疏水性货物的结构变化对药物负载的影响。在这项工作中，我们将这些数据结合起来，建立了一个扩展的配方数据库。测试了不同的分子性质和指纹，以确定它们作为配方特异性混合物描述符的适用性。为不同的描述符子集和载药效率和载药能力的阈值构建了各种分类和回归模型，最佳模型在交叉和外部验证方面都取得了整体良好的统计学结果（平衡准确率为 0.8）。随后，对重要特征进行了解剖，以进行解释，并对 DrugBank 进行了筛选，以寻找这些聚合物可用于开发疏水性药物新制剂的潜在治疗用途案例。最有前途的模型被作为开源软件工具提供给其他研究人员，以测试这些传递系统对潜在新药物候选物的适用性。
