Synthesis and characterization of liposomes encapsulating silver nanoprisms obtained by millifluidic-based production for drug delivery

Abstract

Silver nanoprisms (SNPs) have attracted significant attention due to their surface plasmon resonance behaviour, which is strongly dependent on their size and shape. The enhanced light absorption and scattering capacity of SNPs, make them a promising candidate system for non-invasive imaging and drug delivery in nanoparticle-assisted diagnostics and therapy. However, systemic administration of silver nanoparticles (AgNPs) at high concentrations may result in toxic side-effects, arising from non-targeted bio-distribution. These drawbacks could be mitigated by employing liposomes as carriers for AgNPs. However, there is a lack of systematic studies on production and subsequent physico-chemical characterisation of liposomal systems encapsulating SNPs. The present study therefore investigated the synthesis of liposomes encapsulating SNPs (Lipo/SNPs) using a continuous-flow millimetre-scale reactor, whereby liposome formation was governed by a solvent exchange mechanism. An aqueous phase and an ethanolic lipid phase were conveyed through two separate inlet channels, and subsequently travelled through a serpentine-shaped channel where mixing between the two phases took place. The synthesis process was optimised by varying both liposome formulation and the operating fluidic parameters, including the ratio between inlet flow rates (or flow rate ratio) and the total flow rate. The obtained Lipo/SNPs were characterised for their size and electrostatic charge, using a dynamic light scattering apparatus. Liposome morphology and encapsulation efficiency of SNPs within liposomes were determined by transmission electron microscopy (TEM) imaging. The synthesised negatively charged Lipo/SNP samples were found to have an average size of ~150 nm (size dispersity < 0.3). The AgNPs encapsulation efficiency was equal to 77.48%, with mostly single SNPs encapsulated in liposomes. By using a multiangle TEM imaging approach, quasi-3D images were obtained, further confirming the encapsulation of nanoparticles within liposomes. Overall, the formulation and production technique developed in the present study has potential to contribute towards mitigating challenges associated with AgNP-mediated drug delivery and diagnostics.