Identification of novel cyanoacrylate monomers for use in nanoparticle drug delivery systems prepared by miniemulsion polymerisation - A multistep screening approach.
Astrid Hyldbakk, Yrr Mørch, Sofie Snipstad, Andreas K O Åslund, Geir Klinkenberg, Vu To Nakstad, Ane-Marit Wågbø, Ruth Schmid, Peter P Molesworth
Author Information
Astrid Hyldbakk: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Yrr Mørch: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Sofie Snipstad: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Andreas K O Åslund: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Geir Klinkenberg: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Vu To Nakstad: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Ane-Marit Wågbø: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Ruth Schmid: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Peter P Molesworth: Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
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.
