Hyldbakk Astrid, Mørch Yrr, Snipstad Sofie, Åslund Andreas K O, Klinkenberg Geir, Nakstad Vu To, Wågbø Ane-Marit, Schmid Ruth, Molesworth Peter P
Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Int J Pharm X. 2022 Jul 20;4:100124. doi: 10.1016/j.ijpx.2022.100124. eCollection 2022 Dec.
Poly (alkyl cyanoacrylate) (PACA) polymeric nanoparticles (NPs) are promising drug carriers in drug delivery. However, the selection of commercially available alkyl cyanoacrylate (ACA) monomers is limited, because most monomers were designed for use in medical and industrial glues and later repurposed for drug encapsulation. This study therefore aimed to seek out novel ACA materials for use in NP systems using a toxicity led screening approach. A multistep strategy, including cytotoxicity screening of alcohols as degradation products of PACA (44 alcohols), NPs (14 polymers), and a final study (2 polymers) gave poly (2-ethylhexyl cyanoacrylate) PEHCA as a promising novel PACA candidate. For the first time, this work presents cytotoxicity data on several novel ACAs, PEHCA toxicity data, and miniemulsion polymerisation-based encapsulation of the cabazitaxel and NR688 in novel PACA candidates. Furthermore, several of the ACA candidates were compatible with a wider selection of lipophilic active pharmaceutical ingredients (APIs) commercially available controls. Combined, this work demonstrates the potential benefits of expanding the array of available ACA materials in drug delivery. Novel ACAs have the potential to encapsulate a wider range of APIs in miniemulsion polymerisation processes and may also broaden PACA applicability in other fields.
聚(烷基氰基丙烯酸酯)(PACA)聚合物纳米颗粒(NPs)是药物递送中很有前景的药物载体。然而,市售烷基氰基丙烯酸酯(ACA)单体的选择有限,因为大多数单体最初是为医用和工业胶水设计的,后来才被重新用于药物封装。因此,本研究旨在采用毒性导向筛选方法寻找用于NP系统的新型ACA材料。一种多步骤策略,包括对作为PACA降解产物的醇类(44种醇)、NPs(14种聚合物)进行细胞毒性筛选,以及最后的一项研究(2种聚合物),得出聚(2-乙基己基氰基丙烯酸酯)(PEHCA)是一种很有前景的新型PACA候选物。这项工作首次展示了几种新型ACA的细胞毒性数据、PEHCA的毒性数据,以及新型PACA候选物中基于微乳液聚合的卡巴他赛和NR688的包封情况。此外,几种ACA候选物与更广泛的亲脂性活性药物成分(APIs)商业对照品兼容。综合来看,这项工作证明了在药物递送中扩大可用ACA材料种类的潜在益处。新型ACA有潜力在微乳液聚合过程中封装更广泛的APIs,也可能拓宽PACA在其他领域的适用性。