Identification of novel cyanoacrylate monomers for use in nanoparticle drug delivery systems prepared by miniemulsion polymerisation – A multistep screening approach

• Published in: International journal of pharmaceutics: X 2022-12, Vol.4, p.100124-100124, Article 100124
• Main Authors: Hyldbakk, Astrid, Mørch, Yrr, Snipstad, Sofie, Åslund, Andreas K.O., Klinkenberg, Geir, Nakstad, Vu To, Wågbø, Ane-Marit, Schmid, Ruth, Molesworth, Peter P.
• Format: Article
• Language: English
• Subjects: Cabazitaxel; Drug delivery; Nanoparticle characterisation; Poly(alkyl cyanoacrylate) nanoparticles; Research Paper; Toxicity screening
• ISSN: 2590-1567; 2590-1567
• DOI: 10.1016/j.ijpx.2022.100124

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 in vivo 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 in vivo 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) versus 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. Unlabelled Image • Screening of novel poly(alkylcyanoacrylate) (PACA) materials to broaden PACA nanomedicine potential. • A comprehensive screening process evaluated the toxicity of novel poly(alkylcyanoacrylate) (PACA) materials. • Novel poly(2-ethylhexyl cyanoacrylate) nanoparticles has a promising safety profile. • Novel ACA materials show potential to enable encapsulation of a wider range of APIs.