Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device

Abstract

This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (PEG5K-PLGA55K) matrix. The influence of PEG5K-PLGA55K and conjugated polymers cyanosubstituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (~70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (~70-100 nm) with similar optical properties (quantum yields ~35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG5K-PLGA55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flowbased device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

Low molecular weight PEG–PLGA polymers provide a superior matrix for conjugated polymer nanoparticles in terms of physicochemical properties, biocompatibility and optical/photoacoustic performance

“…The biodegradable copolymer, poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA), has been extensively investigated for drug delivery applications due to its excellent degradation and biocompatibility 23,24 . Additionally, PEG-PLGA has been successfully used as a encapsulating agent for conjugated polymers 25,26 . The lipophilic PLGA chains selfassemble in aqueous solutions to form a hydrophobic matrix which can effectively incorporate lipophilic compounds, whilst the PEG component of the diblock copolymer provides steric stabilisation through orientation of the hydrophilic PEG chains on the surface of the nanoparticles.…”

Organic Small Molecule Based Photothermal Agents with Molecular Rotors for Malignant Breast Cancer Therapy

“…However, it generally shows low mass production efficiency and suboptimal reproducibility with batch to batch size fluctuation . Recently, we and others have shown that microfluidics combined with nanoprecipitation offers large operation window, tunable size and morphology, good reproducibility, and scalable production of PTT agents . TA1 was therefore processed into water‐dispersible nanoparticles with DSPE‐PEG 2000 as the matrix through microfluidics combined with nanoprecipitation (Figure c) .…”

“…Continuous synthesis by using microfluidic glass capillary mixer has gained increasing attention as they exhibit tunable physiochemical properties and efficient mixing . Due to high surface area to volume interaction, microfluidic mixers provide the benefits of enhanced and uniform mixing during NP fabrication.…”

“…They also provide precise control over the size of NPs by varying flow parameters, such as Re and inner to outer flow or velocity ratio (Figure d). The reduction in the size of NPs with Re can be attributed to the fast and uniform mixing in the microfluidic glass capillary through increasing flow rate . At Re 663, the synthesized TA1 NPs show spherical morphologies with an average diameter of around 46 and 45 nm by transmission electron microscope (TEM) and dynamic laser scattering (DLS), respectively (Figure e), which was used for further investigation in vitro and in vivo.…”

Magnetic conjugated polymer nanoparticles doped with a europium complex for biomedical imaging

“…To avoid loss of pegylated surfactant from the CPN surface through biomolecule displacement, an alternative approach using amphiphilic copolymers as matrix forming agents has been tested with some success. 14,15 For example, Abelha et al 14 and Kemal et al 15 have both reported that different -conjugated polymers can be embedded within self-assembling polymer micelles comprised of the copolymer of polylactic-co-glycolic-polyethylene glycol (PLGA-PEG) at extremely high production yields. The resulting CPNs are typically 140-160 nm in size and have high QYs (30-40%) depending on the type of -conjugated polymer used.…”