Sammendrag
Nanoparticles (NPs) offer unique possibilities for medical applications, including the controlled release of cancer drugs, the use as imaging contrast during imaging procedures or the hyperthermic treatment of cancer cells. Flash Nanoprecipitation (FNP) produces NPs to combine these applications in a fast, cheap, and scalable coating process. Until now, FNP was successfully used to encapsulate hydrophobic, organic anti-cancer drugs with block-copolymers [1, 2]. The combination of hydrophobic oleic acid iron oxide NPs (IONPs) with amphiphilic block-copolymers offers promising theranostic abilities when modified with targeting ligands [3]. The use of FNP with a Multi Inlet Vortex Mixer (MIVM) is a promising method to easily coat IONPs with block-copolymers. The FNP coating process needs yet to be tested and understood for various biocompatible block-copolymers (Figure 1).
Amphiphilic block-copolymers based on hydrophilic polyethylene glycol (PEG) and hydrophobic poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) or poly(caprolactone) (PCL) were successfully synthesized. The organic catalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was used to increase biocompatibility of the resulting polymers PEG-PLA, PEG-PLGA and PEG-PCL. The synthesis of hydroxyl terminated poly(acrylic acid) (PAA-OH) followed by the polymerization with PLGA was attempted.
The amphiphilic block-copolymers were used in combination with the stabilizer polysorbate 80 (Tween80) in FNP to form bare polymeric NPs using a MIVM as the reactor. DLS and STEM confirmed particle sizes between 50-100 nm. The addition of 13 ± 2 nm hydrophobic oleic acid coated IONPs yielded an increase in particle size as well as increase in particle stability over time. STEM images showed attachment of single IONPs to the outside of the polymeric NPs. Hydrophobic interactions between the polymer and oleic acid coated IONPs are possible.
To achieve encapsulation of the IONPs, adjustments to the process parameters of FNP should be considered in future research. Additional experiments are required to explore possible drug addition, release mechanisms and hyperthermia behavior of the polymer coated IONPs particles.