Flash Nanoprecipitation: Particle Structure and Stability

Abstract

Flash nanoprecipitation (FNP) is a process that, through rapid mixing, stabilizes an insoluble low molecular weight compound in a nano-sized, polymer-stabilized delivery vehicle. The polymeric components are typically amphiphilic diblock copolymers (BCPs). In order to fully exploit the potential of FNP, factors affecting particle structure, size, and stability must be understood. Here we show that polymer type, hydrophobicity and crystallinity of the small molecule, and small molecule loading levels all affect particle size and stability. Of the four block copolymers (BCP) that we have studied here, poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) was most suitable for potential drug delivery applications due to its ability to give rise to stable nanoparticles, its biocompatibility, and its degradability. We found little difference in particle size when using PLGA block sizes over the range of 5 to 15kDa. The choice of hydrophobic small molecule was important, as molecules with a calculated water-octanol partition coefficient (clogP) below 6 gave rise to particles that were unstable and underwent rapid Ostwald ripening. Studies probing the internal structure of nanoparticles were also performed. Analysis of differential scanning calorimetry (DSC), cryogenic transmission electron microscopy (cryo-TEM), and 1H-NMR experiments support a three-layer core-shell-corona nanoparticle structure.

Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel

“…2Dd) and the TEM images of PPSTs (PEG-PDHA/PEI-PDHA/PTX/siSna/siTwi) (Fig. 2Dc) demonstrated that the additional hydrated layer on the surface of PPSTs could be formed by the PEG, which was consistent with the TEM picture of PEG layer photographed by other researchers [31,32].…”

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

“…FNP has primarily been limited to the encapsulation of hydrophobic molecules with a preferred logP greater than 6 for stable nanoparticle formation [51, 61]. Ion-pairing of weakly hydrophobic and hydrophilic payloads with counter-ions to form hydrophobic salts for complexation with the block copolymer can allow nanoparticle assembly, but this method is not amenable to the loading of most hydrophilic biologics [6, 62].…”

Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

“…Flash NanoPrecipitation (FNP) is a continuous and scalable process for forming NPs that is ideally suited for industrial-scale and low-cost production of targeted encapsulated therapeutics (Johnson and Prud'homme 2003a, b;Pustulka et al 2013;Shen et al 2011;Weissmueller et al 2016;Zhu 2014). In this technique, therapeutic actives are precipitated by rapid micromixing with an antisolvent in the presence of amphiphilic block copolymers.…”