Robert Prud'homme - Profile on Academia.edu (original) (raw)

Papers by Robert Prud'homme

Colloids and Surfaces B: Biointerfaces, Sep 1, 2015

We have developed responsive foam systems for nanoparticle delivery. The foams are easy to make, ... more We have developed responsive foam systems for nanoparticle delivery. The foams are easy to make, stable at room temperature, and can be engineered to break in response to temperature or moisture. Temperature-responsive foams are based on the phase transition of long chain alcohols and could be produced using medical grade nitrous oxide as a propellant. These temperaturesensitive foams could be used for polyacrylic acid (PAA)-based nanoparticle delivery. We also discuss moisture-responsive foams made with soap pump dispensers. Polyethylene glycol (PEG)based nanoparticles or PMMA latex nanoparticles were loaded into Tween 20 foams and the particle size was not affected by the foam formulation or foam break. Using biocompatible detergents, we anticipate this will be a versatile and simple approach to producing foams for nanoparticle delivery with many potential pharmaceutical and personal care applications.

Chemistry of Materials, Jan 11, 2012

The importance of long wavelength and near infra-red (NIR) imaging has dramatically increased due... more The importance of long wavelength and near infra-red (NIR) imaging has dramatically increased due to the desire to perform whole animal and deep tissue imaging. The adoption of NIR imaging is also growing rapidly due to the availability of targeted biological agents for diagnosis and basic medical research that can be imaged in vivo. The wavelength range of 650-1450 nm falls in the region of the spectrum with the lowest absorption in tissue and therefore enables the deepest tissue penetration. This is the wavelength range we focus on with this review. To operate effectively the imaging agents must both be excited and must emit in this long-wavelength window. We review the agents used both for imaging by absorption, scattering, and excitation (such as fluorescence). Imaging agents comprise both aqueous soluble and insoluble species, both organic and inorganic, and unimolecular and supramolecular constructs. The interest in multi-modal imaging, which involves delivery of actives, targeting, and imaging, requires nanocarriers or supramolecular assemblies. Nanoparticles for diagnostics also have advantages in increasing circulation time and increased imaging brightness relative to single molecule imaging agents. This has led to rapid advances in nanocarriers for long-wavelength, NIR imaging.

Journal of Visualized Experiments, Jan 7, 2019

The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. ... more The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can improve bioavailability and modify drug distribution within the body. For hydrophilic drugs like peptides or proteins, encapsulation within NPs can also provide protection from natural clearance mechanisms. There are few techniques for the production of polymeric NPs that are scalable. Flash NanoPrecipitation (FNP) is a process that uses engineered mixing geometries to produce NPs with narrow size distributions and tunable sizes between 30 and 400 nm. This protocol provides instructions on the laboratory-scale production of core-shell polymeric nanoparticles of a target size using FNP. The protocol can be implemented to encapsulate either hydrophilic or hydrophobic compounds with only minor modifications. The technique can be readily employed in the laboratory at milligram scale to screen formulations. Lead hits can directly be scaled up to gram-and kilogram-scale. As a continuous process, scale-up involves longer mixing process run time rather than translation to new process vessels. NPs produced by FNP are highly loaded with therapeutic, feature a dense stabilizing polymer brush, and have a size reproducibility of ± 6%.

Physical review fluids, Jun 20, 2018

The dynamics of molecularly thin graphene sheets in transient flows are important to understand t... more The dynamics of molecularly thin graphene sheets in transient flows are important to understand their behavior in suspension and during processing. Scattering dichroism is used to evaluate changes in the orientation distribution function in dilute suspensions. To evaluate if the graphene sheets behave as flexible sheets or as more rigid flat particles, the results are compared with numerical computations of the single-particle Smoluchowski equation for flat spheroidal particles. In particular, the evolution of the orientation angle in oscillatory flows as a function of increasing amplitude is studied. The results show that even when taking an average rotational diffusivity, the results for the polydisperse graphene sheets show all the hallmarks of the motion of rigid disks, including a frequency doubling of the time-dependent orientation signal. The results indicate that the motion of functionalized graphene sheets in suspension is consistent with flat rigid objects.

Langmuir, Jun 8, 2018

Wet processing of graphene flakes is an important route for creating novel materials. In the pres... more Wet processing of graphene flakes is an important route for creating novel materials. In the present work flow dichroism and small angle light scattering are used to investigate the state of functionalized graphene flakes in suspension and the response to shear flow. In line with expectations from scaling theory, the functionalized graphene sheets are present as flat objects, and flow increases the orientation as for hard spheroidal objects. Comparing the flow induced orientation of thick gold decahedra with the thin graphene flakes shows essentially the same behaviour, except for effects of polydispersity. Adequate prediction of the effects of flow on orientation of graphene flakes is important for designing wet processed graphene based composite materials. In this work we show that quantitative prediction is now possible.

Advanced Materials Technologies

Nanoscale Advances, 2019

Hydrophobic ion pairing has emerged as a method to modulate the solubility of charged hydrophilic... more Hydrophobic ion pairing has emerged as a method to modulate the solubility of charged hydrophilic molecules ranging in class from small molecules to large enzymes. Here we review the application of hydrophobic ion pairing for encapsulating charged hydrophilic molecules into nanocarriers.

Journal of Pharmaceutical Sciences, 2018

Flash NanoPrecipitation is a scalable approach to generate polymeric nanoparticles using rapid mi... more Flash NanoPrecipitation is a scalable approach to generate polymeric nanoparticles using rapid micromixing in specially designed geometries such as a confined impinging jets mixer or a Multi-Inlet Vortex Mixer (MIVM). A major limitation of formulation screening using the MIVM is that a single run requires tens of milligrams of the therapeutic. To overcome this, we have developed a scaled-down version of the MIVM, requiring as little as 0.2 mg of therapeutic, for formulation screening. The redesigned mixer can then be attached to pumps for scale-up of the identified formulation. It was shown that Reynolds number allowed accurate scaling between the 2 MIVM designs. The utility of the small-scale MIVM for formulation development was demonstrated through the encapsulation of a number of hydrophilic macromolecules using inverse Flash NanoPrecipitation with target loadings as high as 50% by mass.

Journal of Visualized Experiments, 2019

Nano letters, Jan 14, 2018

Nanoparticles have shown promise in several biomedical applications, including drug delivery and ... more Nanoparticles have shown promise in several biomedical applications, including drug delivery and medical imaging; however, quantitative prediction of nanoparticle formation processes that scale from laboratory to commercial production has been lacking. Flash NanoPrecipitation (FNP) is a scalable technique to form highly loaded, block copolymer protected nanoparticles. Here, the FNP process is shown to strictly obey diffusion-limited aggregation assembly kinetics, and the parameters that control the nanoparticle size and the polymer brush density on the nanoparticle surface are shown. The particle size, ranging from 40 to 200 nm, is insensitive to the molecular weight and chemical composition of the hydrophobic encapsulated material, which is shown to be a consequence of the diffusion-limited growth kinetics. In a simple model derived from these kinetics, a single constant describes the 46 unique nanoparticle formulations produced here. The polymer brush densities on the nanoparticle...

Drug Metabolism and Pharmacokinetics, 2017

Journal of Biomedical Optics, 2017

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitatio... more Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICGtetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1∶1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations.

New nano-matrix oral formulation of nanoprecipitated cyclosporine A prepared with multi-inlet vortex mixer

International journal of pharmaceutics, Jan 10, 2017

We present a combined nanoparticle (NP) formation process and spray drying to create a nano-matri... more We present a combined nanoparticle (NP) formation process and spray drying to create a nano-matrix formulation of cyclosporine A (CsA) and mannitol (nCsA/MAN) to increase the bioavailability of CsA. CsA NPs were prepared by flash nano precipitation (FNP) using a multi-inlet vortex mixer, and spray-dried with or without mannitol to prepare nCsA/MAN or nanoprecipitated CsA powder (nCsA), respectively. Pre-forming the NPs by FNP uncouples the sizes of the CsA inclusions from the ultimate micron-sized powders produced by spray drying. Both CsA formulations were physicochemically characterized, and a pharmacokinetic study in rats was conducted after oral administration of CsA samples (10mg-CsA/kg). In the nCsA/MAN, CsA NPs dispersed in the mannitol matrix. In water, both the nCsA and nCsA/MAN reconstituted into NP form with average sizes of 317 and 298nm, respectively. In dissolution testing, nCsA and nCsA/MAN exhibited marked improvement in the dissolution with 31- and 41-fold higher dr...

The AAPS journal, 2017

This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carri... more This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9-27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the...

Pharmaceutical research, Sep 25, 2016

This study was undertaken to evaluate the biopharmaceutical properties of cyclosporine A (CsA)-lo... more This study was undertaken to evaluate the biopharmaceutical properties of cyclosporine A (CsA)-loaded nano-matrix particles for inhalation. Nano-matrix particles of CsA with mannitol (nCsAm) were prepared by a flash nano-precipitation technique employing a multi-inlet vortex mixer and evaluated in terms of physicochemical properties, anti-inflammatory effect in the rat model of airway inflammation, pharmacokinetic behavior, and distributions of CsA to side-effect-related organs after intratracheal administration. In nCsAm, spherical nano-particles of CsA were covered with mannitol and the mean particle size was 1.3 μm. The in vitro Next Generation Impactor analysis demonstrated fine inhalation performance with a fine particle fraction value of 65.8%. Intratracheal nCsAm (100 μg-CsA/rat) significantly attenuated the recruitment of inflammatory cells into the airway in the rat model of airway inflammation, followed by suppression of the inflammatory biomarkers. After intratracheal nCs...

Journal of Controlled Release, 2012

Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to... more Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1.5 kg/mol to 9 kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1 nu mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4 h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted in an effort to correlate the protection of the nanocarrier surface from complement binding and activation and in vivo circulation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative size of the hydrophilic and hydrophobic block, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG 5k -PCL 9k and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the sizes of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size, and possibly the clearance from circulation. Suggestions for next step in vitro measurements are made.

Chemistry of Materials, 2010

Near-infrared-to-visible up-conversion of light by rare earth ion-doped nanophosphors (NaYF 4 : Y... more Near-infrared-to-visible up-conversion of light by rare earth ion-doped nanophosphors (NaYF 4 : Yb 3þ ,Er 3þ ) opens new possibilities for improved biolabeling. A major obstacle to applications of upconverting nano phosphors (UCNPs) has been obtaining samples stable in serum media for biological applications. Previous researchers have made UCNPs stable in DI water, but not serum media. In this study, hexagonal phase nanophosphors were prepared using one-step cothermolysis utilizing oleic acid (OA) and trioctyl phosphine (TOP) ligands. Two routes to polymer surface modification of the UCNPs were studied: direct ligand exchange using poly(acrylic acid) (PAA) and amphiphilc copolymer encapsulation via flash nano-precipitation (FNP). FNP-coated UCNPs were produced using three block-copolymers: poly(ethylene glycol)-block-poly(caprolactone) (PEGb-PCL), poly(ethylene glycol)-block-poly(lactic-coglycolic acid) (PEG-b-PLGA), and poly((ethylene glycol)-block-lactic acid) (PEG-b-PLA). Both surface modification routes produced colloidally stable UCNP dispersions in DI water. However, for the first time, we report the successful preparation of colloidal UCNPs stable in buffers and serum media (Leibovitz L-15 media with added fetal bovine serum) using FNP and PEG surface coatings. The stabilizing block-copolymer layer added ca. 15 nm to the diameter of the phosphor crystals. UCNPs assembly of amorphous PLA or PLGA is strikingly different than for crystallizable PCL. These polymer-modified UCNPs provide promising new materials for applications in bioimaging and photodynamic therapy.

Molecular Pharmaceutics, 2017

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and D... more Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics.

Behavior of a suspension in the presence of a potential vortex

The basic equations for suspensions are written, assuming that the carrying fluid is isothermal a... more The basic equations for suspensions are written, assuming that the carrying fluid is isothermal and incompressible and that the particles occupy a negligible volume. The particles are assumed to be nondeformable, spherical, and of the same diameter. The velocity field of the particles and their trajectories are determined, and the evolution of the particle density is investigated. The results are

Macromolecules, 1998

Bonding amorphous polystyrene (PS) and poly(2,6-dimethyl 1,4-phenylene oxide) (PPO) has been carr... more Bonding amorphous polystyrene (PS) and poly(2,6-dimethyl 1,4-phenylene oxide) (PPO) has been carried out in a broad range of temperatures and contact times (t), but always below the glass transition temperature (Tg), in a lap-shear joint geometry. Strength at the symmetric and asymmetric polymer/polymer interfaces develops with t 1/4 and, hence, is diffusion controlled. The development of strength at the homopolymer/miscible blend interface below Tg can be simulated from data for homopolymer/homopolymer interfaces, taking into account the wetting (and "fast diffusion") and diffusion contributions to the development of strength.