Abstract
The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved.
Highlights
The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis
The nanoprecipitation process is implemented in a microfluidic chip with an X-junction configuration (“Droplet - Junction Chip”, depth x width: 190 μm x 390 μm) where particle formation occurs by diffusion and nanoprecipitation (Fig. 2a)
The middle channel is injected with an aqueous solution composed of thiolated hyaluronic acid (HA-SH) and polyethylene glycol- vinyl sulfone (PEG-VS); the side channels are injected with pure acetone to provide the extraction of the water phase (Fig. 2b)
Summary
The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. In the framework of the principles for the production of nanoparticles, nanoprecipitation-based methodologies open new possibilities regarding particle production, size regulation, active agent encapsulation and offer improvements in batch processes being less complicated and time consuming compared to other production techniques[19,21,22,23,24,25,26]. Despite these advantages, limitations such as high batch-to-batch variations, non-homogenous reaction environment[27] and insufficient production rate reveal the need to move towards techniques providing a higher control in the production of nanosystems with well-defined features
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