Microfluidic synthesis of protein-loaded nanogels in a coaxial flow reactor using a design of experiments approach

Whiteley, Zoe; Ho, Hei Ming Kenneth; Gan, Yee Xin; Panariello, Luigia; Gkogkos, Georgios; Gavriilidis, Asterios; Craig, Duncan Q.M.

doi:10.1039/d0na01051k

Cited by 28 publications

(25 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to batch processing, the implemented microfluidic process requires lower polymer concentrations, in agreement with other studies comparing batch protocols with microfluidic processes [ 84 , 85 , 86 , 87 ]. In addition, the proposed strategy allows optimizing the interaction among the chosen compounds.…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

et al. 2021

View full text Add to dashboard Cite

Microfluidics is emerging as a promising tool to control physicochemical properties of nanoparticles and to accelerate clinical translation. Indeed, microfluidic-based techniques offer more advantages in nanomedicine over batch processes, allowing fine-tuning of process parameters. In particular, the use of microfluidics to produce nanoparticles has paved the way for the development of nano-scaled structures for improved detection and treatment of several diseases. Here, ionotropic gelation is implemented in a custom-designed microfluidic chip to produce different nanoarchitectures based on chitosan-hyaluronic acid polymers. The selected biomaterials provide biocompatibility, biodegradability and non-toxic properties to the formulation, making it promising for nanomedicine applications. Furthermore, results show that morphological structures can be tuned through microfluidics by controlling the flow rates. Aside from the nanostructures, the ability to encapsulate gadolinium contrast agent for magnetic resonance imaging and a dye for optical imaging is demonstrated. In conclusion, the polymer nanoparticles here designed revealed the dual capability of enhancing the relaxometric properties of gadolinium by attaining Hydrodenticity and serving as a promising nanocarrier for multimodal imaging applications.

show abstract

Section: Discussionsupporting

confidence: 87%

“…This is due to their influence on the binding process between anionic and cationic blocks. High TPP concentration, i.e., higher availability of the crosslinker, does not always lead to the formation of more stable and smaller NPs if it is not balanced by appropriate flow rates, in accordance with Whiteley et al [ 84 ].…”

Section: Discussionsupporting

confidence: 74%

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Moreover, Whiteley et al used a similar central composite design to predict the encapsulation efficiency of lysozyme in nanogels fabricated via microfluidics. 25 The %EE of lysozyme in nanogels was higher, with at least 54% of the drug input. One possible reason to account for the discrepancy in encapsulation efficiency is that the molecular weight of propranolol and lysozyme is massively different of 259.34 and 14.3 kDa, respectively, even though both are carrying a positive charge.…”

Section: Resultsmentioning

confidence: 96%

Design of Experiment Approach to Modeling the Effects of Formulation and Drug Loading on the Structure and Properties of Therapeutic Nanogels

Craig

Day

2022

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

The physical properties of nanoparticles may affect the uptake mechanism, biodistribution, stability, and other physicochemical properties of drug delivery systems. This study aimed to first develop a model exploring the factors controlling the nanogel physical properties using a single drug (propranolol), followed by an evaluation of whether these models can be applied more generally to a range of drugs. Size, polydispersity, ζ potential, and encapsulation efficiency were investigated using a design of experiment (DOE) approach to optimize formulations by systematically identifying the effects of, and interactions between, parameters associated with nanogel formulation and drug loading. Three formulation factors were selected, namely, chitosan concentration, the ratio between the chitosan and cross-linker—sodium triphosphate—and the ratio between the chitosan and drug. The results indicate that the DOE approach can be used not only to model but also to predict the size and polydispersity index (PDI). To explore the application of these prediction models with other drugs and to identify the relationship between the drug structure and nanogel properties, nanogels loaded with 12 structurally distinct drugs and 6 structurally similar drugs were fabricated at the optimal condition for propranolol in the model. The measured size, PDI, and ζ potential of the nanogels could not be modeled using distinct DOE parameters for dissimilar drugs, indicating that each drug requires a separate analysis. Nevertheless, for drugs with structural similarities, various linear and nonlinear trends were observed in the size, PDI, and ζ potential of nanogels against selected molecular descriptors, indicating that there are indeed relationships between the drug molecular structure and the performance outcomes, which may be modeled and predicted using the DOE approach. In conclusion, the study demonstrates that DOE models can be applied to model and predict the influence of formulation and drug loading on key performance parameters. While distinct models are required for structurally unrelated drugs, it was possible to establish correlations for the drug series investigated, which were based on polarity, hydrophobicity, and polarizability, thereby elucidating the importance of the interactions between the drug and the nanogels based on the nanogel properties and thus deepening the understanding of the drug-loading mechanisms in nanogels.

show abstract

“…Nowadays, one usually distinguishes between micro-and nanogels depending on their characteristic size. Fast development in synthesis techniques [3][4][5][6][7][8] in the last decade resulted in nano-and microgels responsive to various stimuli such as pH [9,10], temperature [9,11,12], electromagnetic radiation [13], ionic strength or electric fields [11,14]. Among typical responses are swelling/collapse transitions or particular rheological properties [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Behaviour of a magnetic nanogel in a shear flow

Novikau¹,

Novak²,

Pyanzina³

et al. 2021

Preprint

View full text Add to dashboard Cite

Magnetic nanogels (MNG) -soft colloids made of polymer matrix with embedded in it magnetic nanoparticles (MNPs)are promising magneto-controllable drug carriers. In order to develop this potential, one needs to clearly understand the relationship between nanogel magnetic properties and its behaviour in a hydrodynamic flow. Considering the size of the MNG and typical time and velocity scales involved in their nanofluidics, experimental characterisation of the system is challenging. In this work, we perform molecular dynamics (MD) simulations combined with the Lattice-Boltzmann (LB) scheme aiming at describing the impact of the shear rate ( γ) on the shape, magnetic structure and motion of an MNG. We find that in a shear flow the centre of mass of a MNG tends to be in the centre of a channel and to move preserving the distance to both walls. The MNG monomers along with translation are involved in two more types of motion, they rotate around the centre of mass and oscillate with respect to the latter. It results in synchronised tumbling and wobbling of the whole MNG accompanied by its volume oscillates. The fact the a MNG is a highly compressible and permeable for the carrier liquid object makes its behaviour different from that predicted by classical Taylor-type models. We show that the frequency of volume oscillations and rotations are identical and are growing function of the shear rate. We find that the stronger magnetic interactions in the MNG are, the higher is the frequency of this complex oscillatory motion, and the lower is its amplitude. Finally, we show that the oscillations of the volume lead to the periodic changes in MNG magnetic energy.

show abstract

Microfluidic synthesis of protein-loaded nanogels in a coaxial flow reactor using a design of experiments approach

Abstract: Ionic gelation is commonly used to generate nanogels but often results in poor control over size and polydispersity. In this work we present a novel approach to the continuous manufacture...

Cited by 28 publications

References 50 publications

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

Design of Experiment Approach to Modeling the Effects of Formulation and Drug Loading on the Structure and Properties of Therapeutic Nanogels

Behaviour of a magnetic nanogel in a shear flow

Contact Info

Product

Resources

About