Publications by authors named "Xavier Banquy"

67 Publications

Phytoglycogen Nanoparticles: Nature-Derived Superlubricants.

ACS Nano 2021 05 7;15(5):8953-8964. Epub 2021 May 7.

Department of Chemistry, University of Toronto, Toronto, Ontario, Canada, M5S 3H6.

Phytoglycogen nanoparticles (PhG NPs), a single-molecule highly branched polysaccharide, exhibit excellent water retention, due to the abundance of close-packed hydroxyl groups forming hydrogen bonds with water. Here we report lubrication properties of close-packed adsorbed monolayers of PhG NPs acting as boundary lubricants. Using direct surface force measurements, we show that the hydrated nature of the NP layer results in its striking lubrication performance, with two distinct confinement-controlled friction coefficients. In the weak- to moderate-confinement regime, when the NP layer is compressed down to 8% of its original thickness under a normal pressure of up to 2.4 MPa, the NPs lubricate the surface with a friction coefficient of 10. In the strong-confinement regime, with 6.5% of the original layer thickness under a normal pressure of up to 8.1 MPa, the friction coefficient was 10. Analysis of the water content and energy dissipation in the confined NP film reveals that the lubrication is governed by synergistic contributions of unbound and bound water molecules, with the former contributing to lubrication properties in the weak- to moderate-confinement regime and the latter being responsible for the lubrication in the strong-confinement regime. These results unravel mechanistic insights that are essential for the design of lubricating systems based on strongly hydrated NPs.
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http://dx.doi.org/10.1021/acsnano.1c01755DOI Listing
May 2021

Recent developments in natural and synthetic polymeric drug delivery systems used for the treatment of osteoarthritis.

Acta Biomater 2021 03 12;123:31-50. Epub 2021 Jan 12.

Faculty of Chemistry, Institute of Polymer and Dye Technology, Lodz University of Technology, Lodz, Poland. Electronic address:

Osteoarthritis (OA), is a common musculoskeletal disorder that will progressively increase in older populations and is expected to be the most dominant cause of disability in the world population by 2030. The progression of OA is controlled by a multi-factorial pathway that has not been completely elucidated and understood yet. However, over the years, research efforts have provided a significant understanding of some of the processes contributing to the progression of OA. Both cartilage and bone degradation processes induce articular cells to produce inflammatory mediators that produce proinflammatory cytokines that block the synthesis of collagen type II and aggrecan, the major components of cartilage. Systemic administration and intraarticular injection of anti-inflammatory agents are the first-line treatments of OA. However, small anti-inflammatory molecules are rapidly cleared from the joint cavity which limits their therapeutic efficacy. To palliate this strong technological drawback, different types of polymeric materials such as microparticles, nanoparticles, and hydrogels, have been examined as drug carriers for the delivery of therapeutic agents to articular joints. The main purpose of this review is to provide a summary of recent developments in natural and synthetic polymeric drug delivery systems for the delivery of anti-inflammatory agents to arthritic joints. Furthermore, this review provides an overview of the design rules that have been proposed so far for the development of drug carriers used in OA therapy. Overall it is difficult to state clearly which polymeric platform is the most efficient one because many advantages and disadvantages could be pointed to both natural and synthetic formulations. That requires further research in the near future.
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http://dx.doi.org/10.1016/j.actbio.2021.01.003DOI Listing
March 2021

Plasmon-Free Polymeric Nanowrinkled Substrates for Surface-Enhanced Raman Spectroscopy of Two-Dimensional Materials.

Langmuir 2021 Jan 21;37(1):322-329. Epub 2020 Dec 21.

Department of Chemical Engineering, Faculty of Engineering & Architectural Science, Ryerson University, Toronto, Ontario M5B 2K3, Canada.

We report plasmon-free polymeric nanowrinkled substrates for surface-enhanced Raman spectroscopy (SERS). Our simple, rapid, and cost-effective fabrication method involves depositing a poly(ethylene glycol)diacrylate (PEGDA) prepolymer solution droplet on a fully polymerized, flat PEGDA substrate, followed by drying the droplet at room conditions and plasma treatment, which polymerizes the deposited layer. The thin polymer layer buckles under axial stress during plasma treatment due to its different mechanical properties from the underlying soft substrate, creating hierarchical wrinkled patterns. We demonstrate the variation of the wrinkling wavelength with the drying polymer molecular weight and concentration (direct relations are observed). A transition between micron to nanosized wrinkles is observed at 5 v % concentration of the lower molecular-weight polymer solution (PEGDA 250). The wrinkled substrates are observed to be reproducible, stable (at room conditions), and, especially, homogeneous at and below the transition regime, where nanowrinkles dominate, making them suitable candidates for SERS. As a proof-of-concept, the enhanced SERS performance of micro/nanowrinkled surfaces in detecting graphene and hexagonal boron nitride (h-BN) is illustrated. Compared to the SiO/Si surfaces, the wrinkled PEGDA substrates significantly enhanced the signature Raman band intensities of graphene and h-BN by a factor of 8 and 50, respectively.
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http://dx.doi.org/10.1021/acs.langmuir.0c02912DOI Listing
January 2021

Superlubricity of Zwitterionic Bottlebrush Polymers in the Presence of Multivalent Ions.

J Am Chem Soc 2020 09 19;142(35):14843-14847. Epub 2020 Aug 19.

Faculty of Pharmacy, Université de Montréal, 2900 Édouard-Montpetit, Montreal, Quebec H3C 3J7, Canada.

In this study, we report lubrication properties of physisorbed zwitterionic bottlebrush polymers in the presence of multivalent ions using the surface force apparatus. Unlike polyelectrolyte brushes, the lubrication properties of which diminish drastically in the presence of multivalent ions at concentrations as low as 0.1 mM, zwitterionic bottlebrush polymers exhibit friction coefficients as low as ∼10 at such concentrations of multivalent ions up to intermediate normal loads. This lubrication ability persists until surface wear occurs at high normal loads. The surface wear is demonstrated to be triggered by the multivalent ions bridging the polymer chains and dehydrating the zwitterionic moieties. Finally, the analysis of the polymer film stability suggests that the partial desorption of polymers in the presence of the ions does not affect the lubrication performance. Therefore, even in the physisorbed state, zwitterionic brushes perform significantly better than covalently grafted polyelectrolyte brushes in the presence of multivalent ions.
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http://dx.doi.org/10.1021/jacs.0c07215DOI Listing
September 2020

Binding mechanism of a de novo coiled coil complex elucidated from surface forces measurements.

J Colloid Interface Sci 2021 Jan 23;581(Pt A):218-225. Epub 2020 Jul 23.

Canada Research Chair in Bio-Inspired Materials and Interfaces, Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada. Electronic address:

We used the Surface Forces Apparatus to elucidate the interaction mechanism between grafted 5 heptad-long peptides engineered to spontaneously form a heterodimeric coiled-coil complex. The results demonstrated that when intimate contact between peptides is reached, binding occurs first via weakly interacting but more mobile distal heptads, suggesting an induced-fit association process. Precise control of the distance between peptide-coated surfaces allowed to quantitatively monitor the evolution of their biding energy. The binding energy of the coiled-coil complex increased in a stepwise fashion rather than monotonically with the overlapping distance, each step corresponding to the interaction between a quantized number of heptads. Surface forces data were corroborated to surface plasmon resonance measurements and molecular dynamics simulations and allowed the calculation of the energetic contribution of each heptad within the coiled-coil complex.
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http://dx.doi.org/10.1016/j.jcis.2020.07.097DOI Listing
January 2021

Superlubrication obtained with mixtures of hydrated ions and polyethylene glycol solutions in the mixed and hydrodynamic lubrication regimes.

J Colloid Interface Sci 2020 Nov 25;579:479-488. Epub 2020 Jun 25.

Faculty of Pharmacy, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.

Hypothesis: Superlubricity is known to dramatically reduce frictional energy consumption and to improve service life of mechanical devices and biological systems. However, reduction of wear during the running-in period of friction pairs, especially under high contact pressures, still remains an unresolved issue affecting all machines.

Experiments: Here the lubrication, adsorption, and conformational properties of hydrated ions and polyethylene glycol (PEG) mixtures were evaluated at different mass fractions and concentrations of PEG and salts by ball-on-disc tribometer, ζ-potential, quartz crystal microbalance with dissipation (QCM-D), and dynamic light scatting (DLS) analyses.

Findings: These mixtures exhibited superlubricity between SiN and sapphire surfaces in a wide range of concentrations and ions valency. Interestingly, a running-in phase shorter than 1 min and low wear rate of 1.85 μm/(N·m) were observed at contact pressures up to 555 MPa, significantly higher to earlier findings. PEG chains retain random coils filling the bulk of the interfacial film without strongly adsorbing on the interfaces but significantly increasing the viscosity of lubricating film, thereby favoring hydrodynamic lubrication. Hydrated ions are strongly adsorbed on the negatively charged ceramic surfaces, ensuring a sustained hydration effect maintaining superlubricity. The outstanding lubrication characteristics of the PEG/ions mixtures were attributed to the synergistic action of hydration and hydrodynamic lubrication, which appears as a promising avenue for developing new green lubricants and has implications for industrial and biological applications.
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http://dx.doi.org/10.1016/j.jcis.2020.06.095DOI Listing
November 2020

Nontoxic Black Phosphorus Quantum Dots Inhibit Insulin Amyloid Fibrillation at an Ultralow Concentration.

iScience 2020 May 10;23(5):101044. Epub 2020 Apr 10.

State Key Laboratory of Chemical Engineering, Tianjin Key Laboratory of Membrane Science and Desalination Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, PR China; School of Marine Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address:

Amyloid are protein aggregates formed by cross β structures assemblies. Inhibiting amyloid aggregation or facilitating its disassembly are considered to be two major effective therapeutic strategies in diseases involving peptide or protein fibrillation such Alzheimer's disease or diabetes. Using thioflavin-T fluorescence, far-UV circular dichroism spectroscopy, and atomic force microscopy, we found nontoxic and biocompatible black phosphorus quantum dots (BPQDs) appear to have an exceptional capacity to inhibit insulin aggregation and to disassemble formed mature fibrils, even at an ultralow concentration (100 ng/mL). The inhibition of fibrillation persists at all stages of insulin aggregation and increases PC12 cells survival when exposed to amyloid fibrils. Molecular dynamics simulations suggest that BPQDs are able to stabilize the α-helix structure of insulin and obliterate the β-sheet structure to promote the fibril formation. These characteristics make BPQDs be promising candidate in preventing amyloidosis, disease treatment, as well as in the storage and processing of insulin.
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http://dx.doi.org/10.1016/j.isci.2020.101044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182724PMC
May 2020

Periphery-confined particulate systems for the management of neurodegenerative diseases and toxicity: Avoiding the blood-brain-barrier challenge.

J Control Release 2020 06 31;322:286-299. Epub 2020 Mar 31.

INRS, Centre Armand-Frappier Santé Biotechnologie, 531 boul. des Prairies, Laval, QC H7V 1B7, Canada.

The blood-brain barrier prevents passage of large and hydrophilic molecules, undermining efforts to deliver most active molecules, proteins and other macromolecules. To date, nanoparticle-assisted delivery has been extensively studied to overcome this challenge but with limited success. On the other hand, for certain brain therapeutic applications, periphery-confined particles could be of immediate therapeutic usefulness. The modulation of CNS dysfunctions from the peripheral compartment is a promising approach, as it does not involve invasive interventions. From recent studies, three main roles could be identified for periphery-confined particles: brain tissue detoxification via the "sink-effect"; a "circulating drug-reservoir" effect to improve drug delivery to brain tissues, and finally, brain vascular endothelium targeting to diagnose or heal vascular-related dysfunctions. These applications are much easier to implement as they do not involve complex therapeutic and targeting strategies and do not require crossing biological barriers. Micro/nano-devices required for such applications will likely be simpler to synthesize and will involve fewer complex materials. Moreover, peripheral particles are expected to be less prone to neurotoxicity and issues related to their diffusion in confined space.
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http://dx.doi.org/10.1016/j.jconrel.2020.03.035DOI Listing
June 2020

Cholic acid-based mixed micelles as siRNA delivery agents for gene therapy.

Int J Pharm 2020 Mar 24;578:119078. Epub 2020 Jan 24.

Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada; Gene Delivery Laboratory, Faculté de pharmacie, Université de Montréal, H3C 3J7 Montréal, QC, Canada. Electronic address:

Gene therapy is a promising tool for the treatment of various cancers but is hindered by the physico-chemical properties of siRNA and needs a suitable vector for the delivery of siRNA to the target tissue. Bile acid-based block copolymers offers certain advantages for the loading and delivery of siRNA since they can efficiently complex siRNA and bile acids are biocompatible endogenous molecules. In this study, we demonstrate the use of lipids as co-surfactants for the preparation of mixed micelles to improve the siRNA delivery of cholic acid-based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were polymerized on the surface of cholic acid to afford a star-shaped block copolymer with four arms (CA-PAGE-b-PEG). The allyl groups of PAGE were functionalized to bear primary or tertiary amines and folic acid was grafted onto the PEG chain end to increase cell uptake. (CA-PAGE-b-PEG) functionalized with either primary or tertiary amines show high siRNA complexation with close to 100% complexation at N/P ratio of 8. Uniform aggregates with diameters between 181 and 188 nm were obtained. DOPE, DSPE-PEG, and DSPE-PEG lipids were added as co-surfactants to help stabilize the nanoparticles in the cell culture media. Mixed micelles had high siRNA loading with close to 100% functionalization at N/P ratio of 16 and diameters ranging from 153 to 221 nm. The presence of lipids in the mixed micelles improved cell uptake with a concomitant siRNA transfection in HeLa and HeLa-GFP model cells, respectively.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119078DOI Listing
March 2020

Spontaneous shrinking of soft nanoparticles boosts their diffusion in confined media.

Nat Commun 2019 09 20;10(1):4294. Epub 2019 Sep 20.

Faculty of Pharmacy, Université de Montréal, PO Box 6128, Succursale Centre-ville, Montréal, QC, H3C 3J7, Canada.

Improving nanoparticles (NPs) transport across biological barriers is a significant challenge that could be addressed through understanding NPs diffusion in dense and confined media. Here, we report the ability of soft NPs to shrink in confined environments, therefore boosting their diffusion compared to hard, non-deformable particles. We demonstrate this behavior by embedding microgel NPs in agarose gels. The origin of the shrinking appears to be related to the overlap of the electrostatic double layers (EDL) surrounding the NPs and the agarose fibres. Indeed, it is shown that screening the EDL interactions, by increasing the ionic strength of the medium, prevents the soft particle shrinkage. The shrunken NPs diffuse up to 2 orders of magnitude faster in agarose gel than their hard NP counterparts. These findings provide valuable insights on the role of long range interactions on soft NPs dynamics in crowded environments, and help rationalize the design of more efficient NP-based transport systems.
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http://dx.doi.org/10.1038/s41467-019-12246-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754464PMC
September 2019

Synergy between Zwitterionic Polymers and Hyaluronic Acid Enhances Antifouling Performance.

Langmuir 2019 12 11;35(48):15535-15542. Epub 2019 Sep 11.

State Key Laboratory of Chemical Engineering, Tianjin Key Laboratory of Membrane Science and Desalination Technology, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , P. R. China.

Challenges associated with nonspecific adsorption of proteins on sensor surfaces have steered the development of novel antifouling materials and strategies. Inspired by human synovial fluid composition and structure, we designed synergistic antifouling coatings with mixtures of hyaluronic acid (HA) and a zwitterionic bottlebrush polymer (BB). Using a fast and convenient online surface modification method, the polymers were immobilized on the Au surface, significantly increasing its hydrophilicity. Using surface plasmon resonance (SPR), a 10:1 ratio of HA to BB was found optimal to provide the best antifouling performance. Bovine serum albumin (BSA) adsorption on HA-BB coated surfaces was 0.2 ng/cm, which was 60 times lower than BB or HA alone and 25 times lower than the commonly accepted ultralow adsorption limit (<5 ng/cm), demonstrating the synergistic effect of HA and BB against nonspecific protein adsorption. This was found to be independent of BSA concentration up to physiological concentrations. Furthermore, the antifouling performance of HA-BB coated surfaces was tested against milk and serum, showing almost 92% lower protein adsorption than that on bare surfaces, suggesting the potential efficacy of this antifouling coating in real life settings.
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http://dx.doi.org/10.1021/acs.langmuir.9b01876DOI Listing
December 2019

Chitosan hydrogel micro-bio-devices with complex capillary patterns via reactive-diffusive self-assembly.

Acta Biomater 2019 11 29;99:211-219. Epub 2019 Aug 29.

Faculty of Pharmacy, Université de Montréal, Montreal, Quebec H3C 3J7, Canada. Electronic address:

We present chitosan hydrogel microfluidic devices with self-assembled complex microcapillary patterns, conveniently formed by a diffusion-reaction process. These patterns in chitosan hydrogels are formed by a single-step procedure involving diffusion of a gelation agent into the polymer solution inside a microfluidic channel. By changing the channel geometry, it is demonstrated how to control capillary length, trajectory and branching. Diffusion of nanoparticles (NPs) in the capillary network is used as a model to effectively mimic the transport of nano-objects in vascularized tissues. Gold NPs diffusion is measured locally in the hydrogel chips, and during their two-step transport through the capillaries to the gel matrix and eventually to embedded cell clusters in the gel. In addition, the quantitative analyses reported in this study provide novel opportunities for theoretical investigation of capillary formation and propagation during diffusive gelation of biopolymers. STATEMENT OF SIGNIFICANCE: Hydrogel micropatterning is a challenging task, which is of interest in several biomedical applications. Creating the patterns through self assembly is highly beneficial, because of the accessible and practical preparation procedure. In this study, we introduced complex self-assembled capillary patterns in chitosan hydrogels using a microfluidic approach. To demonstrate the potential application of these capillary patterns, a vascularized hydrogel with microwells occupied by cells was produced, and the diffusion of gold nanoparticles travelling in the capillaries and diffusing in the gel were evaluated. This model mimics a simplified biological tissue, where nanomedicine has to travel through the vasculature, extravasate into and diffuse through the extracellular matrix and eventually reach targeted cells.
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http://dx.doi.org/10.1016/j.actbio.2019.08.037DOI Listing
November 2019

Multimodal Miniature Surface Forces Apparatus (μSFA) for Interfacial Science Measurements.

Langmuir 2019 12 9;35(48):15500-15514. Epub 2019 Aug 9.

Department of Chemical Engineering , University of California Santa Barbara , Santa Barbara , California 93106 , United States.

Advances in the research of intermolecular and surface interactions result from the development of new and improved measurement techniques and combinations of existing techniques. Here, we present a new miniature version of the surface forces apparatus-the μSFA-that has been designed for ease of use and multimodal capabilities with the retention of the capabilities of other SFA models including accurate measurements of the surface separation distance and physical characterization of dynamic and static physical forces (i.e., normal, shear, and friction) and interactions (e.g., van der Waals, electrostatic, hydrophobic, steric, and biospecific). The small physical size of the μSFA, compared to previous SFA models, makes it portable and suitable for integration into commercially available optical and fluorescence light microscopes, as demonstrated here. The large optical path entry and exit ports make it ideal for concurrent force measurements and spectroscopy studies. Examples of the use of the μSFA in combination with surface plasmon resonance (SPR) and Raman spectroscopy measurements are presented. Because of the short working distance constraints associated with Raman spectroscopy, an interferometric technique was developed and applied to calculate the intersurface separation distance based on Newton's rings. The introduction of the μSFA will mark a transition in SFA usage from primarily physical characterization to concurrent physical characterization with in situ chemical and biological characterization to study interfacial phenomena, including (but not limited to) molecular adsorption, fluid flow dynamics, the determination of surface species and morphology, and (bio)molecular binding kinetics.
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http://dx.doi.org/10.1021/acs.langmuir.9b01808DOI Listing
December 2019

Interfacial Forces across Ionic Liquid Solutions: Effects of Ion Concentration and Water Domains †.

Langmuir 2019 Dec 2;35(48):15585-15591. Epub 2019 Aug 2.

Faculty of Pharmacy , Université de Montréal , 2900 Édouard-Montpetit , Montreal H3C 3J7 , Canada.

Using the surface force apparatus (SFA), the interaction forces between mica surfaces across ionic liquid (IL) solutions are studied. The IL solution, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide in propylene carbonate solvent, is used at different concentrations to elucidate the ions' conformation at the interface from the analysis of short-range structural forces. A direct correlation between the ion layer thickness at the interface and the IL molar fraction in the solution is observed, suggesting conformational changes relative to the ion packing density. In addition, effects of large microscopic and macroscopic water domains at the interface are investigated. The microscopic water domains induced significant adhesion at contact because of the long-range capillary forces, which are found to depend on solvent concentration. The macroscopic water domains entirely cover the interaction area, ensuring that the long-range interfacial interactions occur entirely across the aqueous electrolyte solution with dissolved IL ions as the electrolyte. These results help elucidate the interfacial interactions in IL-charged solid interfaces with practical importance in green energy storage, catalysis, and lubrication.
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http://dx.doi.org/10.1021/acs.langmuir.9b02011DOI Listing
December 2019

Coiled Coil Affinity-Based Systems for the Controlled Release of Biofunctionalized Gold Nanoparticles from Alginate Hydrogels.

Biomacromolecules 2019 05 23;20(5):1926-1936. Epub 2019 Apr 23.

Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit , École Polytechnique de Montréal , Montréal H3T 1J4 , Québec , Canada.

Affinity-based systems represent a promising solution to control the delivery of therapeutics using hydrogels. Here, we report a hybrid system that is based on the peptidic E/K coiled coil affinity pair to mediate the release of gold nanoparticles (NPs) from alginate scaffolds. On one hand, the gold NPs were functionalized with the Ecoil-tagged epidermal growth factor (EGF). The bioactivity of the grafted EGF and the bioavailability of the Ecoil moiety were confirmed by EGF receptor phosphorylation assays and by capturing the functionalized NPs on a Kcoil-derivatized surface. On the other hand, alginate chains were modified with azido-homoalanine Kcoil (Aha-Kcoil) by azide-alkyne click chemistry. The hybrid system was formed by dispersing NPs functionalized with the Ecoil-tagged EGF in alginate hydrogels containing either 0, 10, or 20% of Kcoil-modified alginate (Alg-Kcoil). With 20% of Alg-Kcoil, the release of Ecoil-functionalized NPs was reduced by half when compared to the release of NPs without Ecoil, whereas little to no differences were noticed with either 0 or 10% of Alg-Kcoil. Differential dynamic microscopy was used to determine the diffusion coefficient of the NPs, and the results showed a decrease in the diffusion coefficient of Ecoil-functionalized NPs, when compared to bare PEGylated NPs. Altogether, our data demonstrated that the E/K coiled coil system can control the release of NPs in a high Kcoil content alginate gel, opening diverse applications in drug delivery.
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http://dx.doi.org/10.1021/acs.biomac.9b00137DOI Listing
May 2019

Subtle and unexpected role of PEG in tuning the penetration mechanisms of PLA-based nano-formulations into intact and impaired skin.

Int J Pharm 2019 May 27;563:79-90. Epub 2019 Feb 27.

Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada. Electronic address:

We present a systematic study of the role of poly(ethylene glycol) (PEG) content in NPs on drug skin absorption. Cholecalciferol-loaded NPs of 100 nm of diameter were prepared by flash nanoprecipitation from PLA-b-PEG copolymers of various PEG lengths. As PEG content increased in the polymer, we observed a transition from a frozen solid particle structure to a more dynamic particle structure. Skin absorption studies showed that polymer composition influenced drug penetration depending on skin condition (intact or impaired). In intact skin, highly PEGylated NPs achieved the best skin absorption, even if the penetration differences between the NPs were low. In impaired skin, on the contrary, non-PEGylated NPs (PLA NPs) promoted a strong drug deposition. Further investigations revealed that the strong drug accumulation from PLA NPs in impaired skin was mediated by aggregation and sedimentation of NPs due to the release of charged species from the skin. In contrast, the dynamic structure of highly PEGylated NPs promoted wetting of the surface and interactions with skin lipids, improving drug absorption in intact skin. Since NPs structure and surface properties determine the drug penetration mechanisms at the NP-skin interface, this work highlights the importance of properly tuning NPs composition according to skin physiopathology.
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http://dx.doi.org/10.1016/j.ijpharm.2019.02.039DOI Listing
May 2019

Nanoparticle heterogeneity: an emerging structural parameter influencing particle fate in biological media?

Nanoscale 2019 Jan;11(2):383-406

Centre INRS Institut Armand-Frappier, 531, boul. des Prairies, Laval, QC H7V 1B7, Canada.

Drug nanocarriers' surface chemistry is often presumed to be uniform. For instance, the polymer surface coverage and distribution of ligands on nanoparticles are described with averaged values obtained from quantification techniques based on particle populations. However, these averaged values may conceal heterogeneities at different levels, either because of the presence of particle sub-populations or because of surface inhomogeneities, such as patchy surfaces on individual particles. The characterization and quantification of chemical surface heterogeneities are tedious tasks, which are rather limited by the currently available instruments and research protocols. However, heterogeneities may contribute to some non-linear effects observed during the nanoformulation optimization process, cause problems related to nanocarrier production scale-up and correlate with unexpected biological outcomes. On the other hand, heterogeneities, while usually unintended and detrimental to nanocarrier performance, may, in some cases, be sought as adjustable properties that provide NPs with unique functionality. In this review, results and processes related to this issue are compiled, and perspectives and possible analytical developments are discussed.
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http://dx.doi.org/10.1039/c8nr04916eDOI Listing
January 2019

Lubrication and Wear Protection of Micro-Structured Hydrogels Using Bioinspired Fluids.

Biomacromolecules 2019 01 4;20(1):326-335. Epub 2018 Dec 4.

Ingénierie des Matériaux Polymères, IMP- CNRS UMR 5223 , Université de Lyon, Université Claude Bernard Lyon 1 , 15 Boulevard Latarjet , 69622 Villeurbanne Cedex , France.

We report the fabrication and the use of a bioinspired synovial fluid acting as a lubricant fluid and antiwear agent at soft and porous chitosan hydrogel tribopairs. This synthetic synovial fluid is composed of sodium hyaluronate (HA) and a bottle-brush polymer (BB) having a polycationic attachment group and polyzwitterionic pendant chains. The 2.5% chitosan hydrogel plugs are organized in a bilayered structure exposing a thin and dense superficial zone (SZ), covering a porous deep zone (DZ), and exhibiting microchannels perpendicularly aligned to the SZ. Using a low-load tribometer, the addition of HA lubricating solution at the hydrogel-hydrogel rubbing contact drastically decreased the coefficient of friction (CoF) from μ = 0.20 ± 0.01 to 0.04 ± 0.01 on the DZ configuration and from μ = 0.31 ± 0.01 to 0.08 ± 0.01 on the SZ surface when increasing the HA concentration from 0 to 1000 μg/mL and its molecular mass from 10 to 1500 kDa, similar to what was found when using the BB polymer alone. When combining the BB polymer and the 1500 kDa HA, the CoF remained stable at μ = 0.04 ± 0.01 for both studied contact configurations, highlighting the synergistic interaction of the two macromolecules. Hydrogel wear was characterized by assessing the final gel surface roughness by the means of an interferometer. Increasing HA concentration and molecular weight plus the addition of the BB polymer led to a dramatic surface wear protection with a final gel surface roughness of the hydrogels similar to the untested gels. In brief, the BB polymer in combination with high molecular weight HA is a potential lubricating fluid as well as a wear resistant agent for soft materials lubrication and wear protection.
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http://dx.doi.org/10.1021/acs.biomac.8b01311DOI Listing
January 2019

Biomimetic Bottlebrush Polymer Coatings for Fabrication of Ultralow Fouling Surfaces.

Angew Chem Int Ed Engl 2019 01 5;58(5):1308-1314. Epub 2018 Dec 5.

Faculty of Pharmacy, Université de Montréal, 2900 Édouard-Montpetit, Montreal, Quebec, H3C 3J7, Canada.

Demand for long-lasting antifouling surfaces has steered the development of accessible, novel, biocompatible and environmentally friendly materials. Inspired by lubricin (LUB), a component of mammalian synovial fluid with excellent antifouling properties, three block polymers offering stability, efficacy, and ease of use were designed. The bottlebrush-structured polymers adsorbed strongly on silica surfaces in less than 10 minutes by a simple drop casting or online exposure method and were extremely stable in high-salinity solutions and across a wide pH range. Antifouling properties against proteins and bacteria were evaluated with different techniques and ultralow fouling properties demonstrated. With serum albumin and lysozyme adsorption <0.2 ng cm , the polymers were 50 and 25 times more effective than LUB and known ultralow fouling coatings. The antifouling properties were also tested under MPa compression pressures by direct force measurements using surface forces apparatus. The findings suggest that these polymers are among the most robust and efficient antifouling agents currently known.
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http://dx.doi.org/10.1002/anie.201808987DOI Listing
January 2019

GM1-Binding Conjugates To Improve Intestinal Permeability.

Mol Pharm 2019 01 29;16(1):60-70. Epub 2018 Nov 29.

Faculty of Pharmacy , Université de Montréal , H3C 3J7 Montréal , Québec , Canada.

Drugs and proteins with poor intestinal permeability have a limited oral bioavailability. To remediate this problem, a receptor-mediated endocytosis and transcytosis approach was explored. Indeed, the nontoxic β subunit of cholera toxin (CTB) can cross the intestinal barrier by binding to receptor GM1. In this study, we explored the use of GM1-binding peptides and CTB as potential covalent carriers of poorly permeable molecules. GM1-binding peptides (G23, P3) and CTB were conjugated to poorly permeable fluorescent probes such as fluorescein isothiocyanate (FITC) and albumin-FITC using triethylene glycol spacers and click chemistry. The affinity of the peptide conjugates with receptor GM1 was confirmed by isothermal titration calorimetry or microscale thermophoresis, and the results suggested the involvement of nonspecific interactions. Conjugating the model drugs to G23 and P3 improved the internalization into Caco-2 and T84 cells, although the process was not dependent on the amount of GM1 receptor. However, conjugation of bovine serum albumin FITC to CTB increased the internalization in the same cells in a GM1-dependent pathway. Peptide conjugates demonstrated a limited permeability through a Caco-2 monolayer, whereas G23 and CTB conjugates slightly enhanced permeability through a T84 cell monolayer compared to model drugs alone. Since CTB can improve the permeability of large macromolecules such as albumin, it is an interesting carrier for the improvement of oral bioavailability of various other macromolecules such as heparins, proteins, and siRNAs.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00776DOI Listing
January 2019

Adequate Reducing Conditions Enable Conjugation of Oxidized Peptides to Polymers by One-Pot Thiol Click Chemistry.

Bioconjug Chem 2018 11 26;29(11):3866-3876. Epub 2018 Oct 26.

Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit , École Polytechnique de Montréal , P.O. Box 6079, succ. Centre-Ville, Montréal , Quebec , Canada H3C 3A7.

Thiol(-click) chemistry has been extensively investigated to conjugate (bio)molecules to polymers. Handling of cysteine-containing molecules may however be cumbersome, especially in the case of fast-oxidizing coiled-coil-forming peptides. In the present study, we investigated the practicality of a one-pot process to concomitantly reduce and conjugate an oxidized peptide to a polymer. Three thiol-based conjugation chemistries (vinyl sulfone (VS), maleimide, and pyridyldithiol) were assayed along with three reducing agents (tris(2-carboxyethyl)phosphine (TCEP), dithiothreitol, and β-mercaptoethanol). Seven out of the nine possible combinations significantly enhanced the conjugation yield, provided that an adequate concentration of reductant was used. Among them, the coincubation of an oxidized peptide with TCEP and a VS-modified polymer displayed the highest level of conjugation. Our results also provide insights into two topics that currently lack consensus: TCEP is stable in 10 mM phosphate buffered saline and it reacts with thiol-alkylating agents at submillimolar concentrations, and thus should be carefully used in order to avoid interference with thiol-based conjugation reactions.
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http://dx.doi.org/10.1021/acs.bioconjchem.8b00684DOI Listing
November 2018

Effect of surface chemistry of polymeric nanoparticles on cutaneous penetration of cholecalciferol.

Int J Pharm 2018 Dec 11;553(1-2):120-131. Epub 2018 Oct 11.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEP UMR 5007, 43 Boulevard du 11 novembre 1918, F-69100 Villeurbanne, France. Electronic address:

We investigated the influence of nanoparticle (NP) surface composition on different aspects of skin delivery of a lipophilic drug: chemical stability, release and skin penetration. Cholecalciferol was chosen as a labile model drug. Poly(lactic acid) (PLA)-based NPs without surface coating, with a non-ionic poly(ethylene glycol) (PEG) coating, or with a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating were prepared using flash nanoprecipitation. Process was optimized to obtain similar hydrodynamic diameters. Polymeric NPs were compared to non-polymeric cholecalciferol formulations. Cholecalciferol stability in aqueous medium was improved by polymeric encapsulation with a valuable effect of a hydrophilic coating. However, the in vitro release of the drug was found independent of the presence of any polymer, as for the drug penetration in an intact skin model. Such tendency was not observed in impaired skin since, when stratum corneum was removed, we found that a neutral hydrophilic coating around NPs reduced drug penetration compared to pure drug NPs and bare PLA NPs. The nature of the hydrophilic block (PEG or PMPC) had however no impact. We hypothesized that NPs surface influenced drug penetration in impaired skin due to different electrostatic interactions between NPs and charged skin components of viable skin layers.
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http://dx.doi.org/10.1016/j.ijpharm.2018.09.046DOI Listing
December 2018

Quantification of peptides in human synovial fluid using liquid chromatography-tandem mass spectrometry.

Talanta 2018 Aug 6;186:124-132. Epub 2018 Apr 6.

Faculty of Pharmacy, Université de Montreal, Montreal, QC, Canada H3C 3J7. Electronic address:

A method to explore the stability of two anti-inflammatory peptides in human synovial fluid (HSF) has been developed and validated using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The two peptides are BQ123 Cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu, Mw = 610.7) and R-954 (AcOrn[Oic, (αMe)Phe, DβNal, Ile]desArg-bradykinin, Mw = 1194.4). Human synovial fluid samples were analyzed after a protein precipitation step with acetonitrile and dilution with mobile phase. DMSO was used as anti-adsorptive agent. We used an octyl silane column with formic acid (0.1%, v/v) in water as the aqueous mobile phase and acetonitrile isopropanol-formic acid (20:80, 0.1 v/v) as the organic mobile phase and 0.7 mL/min flow rate. The peptides CY-771 and pepstatin A were used as internal standards. Selective detection was performed by tandem mass spectrometry with a heated electrospray source (HESI), operated in positive ionization mode and in selected reaction monitoring acquisition (SRM). The method limit of quantification (injection volume = 10 µL) was 0.17 ng and 1.2 ng, corresponding to 28 and 102 nmol L for BQ123 and R-954 respectively in human synovial fluid. Calibration curves obtained using matrix-matched calibration standards and internal standard were linear from 20 to 1000 nmol L. Precision values (%R.S.D.) were ≤ 14% in the entire linear range. Accuracy measured at a low and a high concentration level ranged from 93.1% to 102%. The recoveries (at 800 nmol L) were 96.4% for BQ123 and 102.0% for R-954. The method was successfully applied to follow the degradation kinetics of both peptides in human synovial fluid from arthritic patients during 72 h.
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http://dx.doi.org/10.1016/j.talanta.2018.03.105DOI Listing
August 2018

Crystal structure of 2-oxopyrrolidin-3-yl 4-(2-phenyl-diazen-1-yl)benzoate.

Acta Crystallogr E Crystallogr Commun 2018 Apr 6;74(Pt 4):458-460. Epub 2018 Mar 6.

Otto Maass Chemistry Building, Office 430, Chemistry Department, McGill University, 801 Sherbrooke St. W., Montreal, Quebec, Canada, H3A 0B8.

In the title compound, CHNO, the plane of the pyrrolidone ring is inclined at an angle of 59.791 (2)° to that of the azo-benzene segment, which adopts a configuration close to planar. In the crystal, mol-ecules are oriented pairwise by (2-oxopyrrolidin-3-yl)-oxy moieties at an angle of 76.257 (3)°, linked by hydrogen bonds and π-stacking inter-actions, forming zigzag supra-molecular chains parallel to [010] further linked additional C-H⋯π inter-actions.
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http://dx.doi.org/10.1107/S205698901800333XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946967PMC
April 2018

Unified Scaling of the Structure and Loading of Nanoparticles Formed by Diffusion-Limited Coalescence.

Langmuir 2018 05 9;34(20):5772-5780. Epub 2018 May 9.

Faculté de Pharmacie , Université de Montréal , C.P. 6128, Succursale Centre-ville , Montréal , Québec H3C 3J7 , Canada.

The present study establishes the scaling laws describing the structure of spherical nanoparticles formed by diffusion-limited coalescence. We produced drug-loaded nanoparticles from a poly(ethylene glycol)-poly(d,l-lactic acid) diblock polymer (PEG- b-PLA) by the nanoprecipitation method using different types of micromixing chambers to explore multiple mixing regimes and characteristic times. We first show that the drug loading of the nanoparticles is not controlled by the mixing time but solely by the drug-to-polymer ratio (D:P) in the feed and the hydrophobicity of the drug scaled via the partition coefficient P. We then procure compelling evidence that particles formed via diffusion/coalescence exhibit a relative distribution of PEG blocks between the particle core and its shell that depends only on mixing conditions (not on D:P). Scaling laws of PEG relative distribution and chain surface density were derived in different mixing regimes and showed excellent agreement with experimental data. In particular, results made evident that PEG blocks entrapment in the core of the particles occurs in the slow-mixing regime and favors the overloading (above the thermodynamic limit) of the particles with hydrophilic drugs. The present analysis compiles effective guidelines for the scale up of nanoparticles structure and properties with mixing conditions, which should facilitate their future translation to medical and industrial settings.
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http://dx.doi.org/10.1021/acs.langmuir.8b00652DOI Listing
May 2018

Bioinspired microstructures of chitosan hydrogel provide enhanced wear protection.

Soft Matter 2018 Mar;14(11):2068-2076

Université de Lyon, Université Claude Bernard Lyon 1, CNRS, IMP, UMR 5223, 15 Boulevard Latarjet, F-69622, Villeurbanne, France.

We describe the fabrication of physical chitosan hydrogels exhibiting a layered structure. This bilayered structure, as shown by SEM and confocal microscopy, is composed of a thin dense superficial zone (SZ), covering a deeper zone (DZ) containing microchannels orientated perpendicularly to the SZ. We show that such structure favors diffusion of macromolecules within the hydrogel matrix up to a critical pressure, σ, above which channels were constricted. Moreover, we found that the SZ provided a higher wear resistance than the DZ which was severely damaged at a pressure equal to the elastic modulus of the gel. The coefficient of friction (CoF) of the SZ remained independent of the applied load with μ = 0.38 ± 0.02, while CoF measured at DZ exhibited two regimes: an initial CoF close to the value found on the SZ, and a CoF that decreased to μ = 0.18 ± 0.01 at pressures higher than the critical pressure σ. Overall, our results show that internal structuring is a promising avenue in controlling and improving the wear resistance of soft materials such as hydrogels.
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http://dx.doi.org/10.1039/c8sm00215kDOI Listing
March 2018

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

Mol Pharm 2018 03 6;15(3):1266-1276. Epub 2018 Feb 6.

Département de Chimie , Université de Montréal , CP 6128, Succursale Centre-ville, Montréal , Quebec H3C 3J7 , Canada.

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG)) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.
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http://dx.doi.org/10.1021/acs.molpharmaceut.7b01091DOI Listing
March 2018

Unraveling the Correlations between Conformation, Lubrication, and Chemical Stability of Bottlebrush Polymers at Interfaces.

Biomacromolecules 2017 12 25;18(12):4002-4010. Epub 2017 Oct 25.

Canada Research Chair in Bioinspired Materials, Faculty of Pharmacy, Université de Montréal , Montréal, Quebec, Canada.

In the present study, we monitored the conformation and chemical stability of a hydrophilic bottlebrush (BB) polymer in pure water and buffered saline solutions. We correlated these parameters to lubricating and wear protecting properties. Using the surface forces apparatus (SFA), we show that the BB polymer partially adsorbs on mica surfaces and extends half its contour length toward the aqueous media. This conformation gives rise to a strong repulsive interaction force when surfaces bearing BB polymer chains are pressed against each other. Analysis of these repulsive forces demonstrated that the adsorbed polymer chains could be described as end-attached elastic rods. After 2 months of aging at temperatures ranging from 4 to 37 °C, partial scission of the BB polymer's lateral chains was observed by gel permeation chromatography with a half-life time of the polymer of at least two years. The thickness of the BB polymer layer assessed by SFA appeared to quickly decrease with aging time and temperature, which was mainly caused by the adsorption to the substrate of the released lateral chains. The gradual loss of the BB polymer lateral chains did not significantly impact the tribological properties of the BB polymer solution nor its wear protection capacity. The friction coefficient between mica surfaces immersed in the BB polymer solution was μ = 0.031 ± 0.002, was independent of the aging conditions, and remained constant up to an applied pressure P = 0.2 to 0.25 MPa. Altogether, this study demonstrates that, besides the gradual loss of lateral chains, the BB polymer is still able to perform adequately as a lubricant and wear protecting agent over a time period suitable for in vivo administration.
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http://dx.doi.org/10.1021/acs.biomac.7b01063DOI Listing
December 2017

Non-covalent formulation of active principles with dendrimers: Current state-of-the-art and prospects for further development.

J Control Release 2017 Oct 6;264:288-305. Epub 2017 Sep 6.

Laboratoire de Nanotechnologie Pharmaceutique, Jean-Coutu Building, Faculty of Pharmacy, Université de Montréal, 2900 Édouard-Montpetit, Montreal, Quebec H3T 1J4, Canada.

During the last three decades, dendrimers, nano-sized highly-branched fractal-like symmetrical macromolecules, have been intensively studied as promising candidates for application as drug-delivery carriers. Among other important characteristics arising from their unique and highly-controlled architecture, size and surface properties, the possibility of hosting guest molecules in internal voids represents a key advantage underlying the potential of dendrimers as non-covalent drug-encapsulating agents. The impressive amount of accumulating experimental results to date allows researchers to identify the most important and promising theoretical and practical aspects of the use of dendrimers for this purpose. This review covers the main factors, phenomena, and mechanisms involved in this drug-vectorization approach, including mechanisms of non-covalent dendrimer-drug association, dendrimer-dendrimer interactions, as well as biological properties relevant to the host dendrimers. A discussion is then provided to illustrate some successful existing formulation strategies as well as to propose some new possible ones to optimize further development of the field.
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http://dx.doi.org/10.1016/j.jconrel.2017.09.002DOI Listing
October 2017