Aerosolization of poly(sulfobetaine) microparticles that encapsulate therapeutic antibodies.

Pulmonary delivery of protein therapeutics poses significant challenges that have not been well addressed in the research literature or practice. In fact, there is currently only one commercial protein therapeutic that is delivered through aerosolization and inhalation. In this study, we propose a drug delivery strategy that enables a high-concentration dosage for the pulmonary delivery of antibodies as an aerosolizable solid powder with desired stability. We utilized zwitterionic polymers for their promising properties as drug delivery vehicles and synthesized swellable, biodegradable poly(sulfo-betaine) (pSB) microparticles. The microparticles were loaded with Immunoglobulin G (IgG) as a model antibody. We quantified the microparticle size and morphology, and the particles were found to have an average diameter of 1.6 µm, falling within the optimal range (~1-5 µm) for pulmonary drug delivery. In addition, we quantified the impact of the crosslinker to monomer ratio on particle morphology and drug loading capacity. The results showed that there is a trade-off between desired morphology and drug loading capacity as the crosslinker density increases. In addition, the particles were aerosolized, and our data indicated that the particles remained intact and retained their initial morphology and size after aerosolization. The combination of morphology, particle size, antibody loading capacity, low cytotoxicity, and ease of aerosolization support the potential use of these particles for pulmonary delivery of protein therapeutics.

Biodegradable zwitterionic poly(carboxybetaine) microgel for sustained delivery of antibodies with extended stability and preserved function.

Many recent innovative treatments are based on monoclonal antibodies (mAbs) and other protein therapies. Nevertheless, sustained subcutaneous, oral or pulmonary delivery of such therapeutics is limited by the poor stability, short half-life, and non-specific interactions between the antibody (Ab) and delivery vehicle. Protein stabilizers (osmolytes) such as carboxybetaine can prevent non-specific interactions within proteins. In this work, a biodegradable zwitterionic poly(carboxybetaine), pCB, based microgel covalently crosslinked with tetra(ethylene glycol) diacrylate (TTEGDA) was synthesized for Ab encapsulation. The resulting microgels were characterized via FTIR, diffusion NMR, small-angle neutron scattering (SANS), and cell culture studies. The microgels were found to contain up to 97.5% water content and showed excellent degradability that can be tuned with crosslinking density. Cell compatibility of the microgel was studied by assessing the toxicity and immunogenicity in vitro. Cells exposed to microgel showed complete viability and no pro-inflammatory secretion of interleukin 6 (IL6) or tumor necrosis factor-alpha (TNFα). Microgel was loaded with Immunoglobulin G (as a model Ab), using a post-fabrication loading technique, and Ab sustained release from microgels of varying crosslinking densities was studied. The released Abs (especially from the high crosslinked microgels) proved to be completely active and able to bind with Ab receptors. This study opens a new horizon for scientists to use such a platform for local delivery of Abs to the desired target with minimized non-specific interactions.

Diffusion, Interactions, and Disparate Kinetic Trapping of Water-Hydrocarbon Mixtures in Nanoporous Solids.

Mixed fluids confined in porous solid hosts present challenges for the accurate characterization of individual-component behavior. NMR diffusometry with chemical resolution is used to identify unexpected loading- and composition-dependent anomalous diffusion in water/cyclohexane mixtures confined to solid nanoporous glass (NPG) hosts. Diffusion NMR results indicate that data obtained on pure-component liquids in confinement cannot be extrapolated to their nonideal liquid mixtures confined in the same solid host. Loading-dependent data must be obtained on each component in the confined mixture in order to determine which of the liquid components exhibits chemical affinity for the host and, conversely, which of the components exhibits anomalous diffusivity. Most notably, NMR diffusometry revealed that cyclohexane diffusivity varied by 2 orders of magnitude in a water-rich mixture depending on the total fluid loading in the NPG host, ranging from anomalously high diffusivities that significantly exceeded that for pure cyclohexane in NPG at low fluid loadings to kinetically trapped sequestration at high fluid loadings. NMR diffusometry indicates that nonideal solution behavior in fluids confined within nanoporous hosts may have practical implications for enhanced oil recovery methods. Specifically, kinetic trapping of hydrocarbons in water-flooding regimes can result from complex liquid-vapor equilibrium that is significantly perturbed from that which exists in bulk or microporous confinement.

Interactions between Biomolecules and Zwitterionic Moieties: A Review.

Throughout the past decade, zwitterionic moieties have gained attention as constituents of biocompatible materials for exhibiting superhydrophilic properties that prevent nonspecific protein adsorption. Researchers have been working to synthesize zwitterionic materials for diverse biomedical applications such as drug delivery, protein stabilization, and surface modification of implantable materials. These zwitterionic materials have been used in assorted architectures, including protein conjugates, surface coatings, nanoparticles, hydrogels, and liposomes. Herein, we summarize recent advancements that further our understanding of interactions between biomolecules and zwitterionic moieties. We focus on the solution behavior of zwitterions and zwitterionic polymers and the molecular interactions between these molecules and biomolecules as determined by both experimental and theoretical studies. Further, we discuss the implications of using such interactions in vivo and how zwitterionic moieties may be incorporated to facilitate targeted delivery of proteins, genes, or small molecules. Finally, we discuss current knowledge gaps that need to be addressed to advance the field.

Effect of salinity, Mg2+ and SO42- on "smart water"-induced carbonate wettability alteration in a model oil system.

HYPOTHESIS: We present a systematic study of the "smart water" induced wettability alteration. This process is believed to be greatly affected by the brine salinity and the presence of Mg2+ and SO42- in the brine. EXPERIMENTS AND MODELLING: To characterize the wettability alteration, we perform spontaneous imbibition measurement using Indiana limestone cores and a model oil with added naphthenic acid. Both single-electrolyte-based and seawater-based "smart water" are tested to investigate the effect of Mg2+, SO42- and salinity on wettability alteration. Rock/brine and oil/brine zeta potentials are measured, and the electrostatic component of disjoining pressure is calculated to understand the role of electrostatics in the wettability alteration. The surface concentration of charged species on the limestone surface is analyzed based on a natural carbonate surface complexation model (SCM). FINDINGS: Both the reduction of Na+ and addition of SO42- are found to contribute to wettability alteration. Mg2+ is found to be unfavorable for wettability alteration. Ca2+ is believed to facilitate SO42- with wettability alteration based on the comparison between the single-electrolyte-based and seawater-based brines. The reduction of the Na+ surface complexation (>CaOH⋯Na+0.25) in low salinity brines is believed to be a critical mechanism responsible for wettability alteration based on the SCM calculations.

Process simulation of ethanol production from biomass gasification and syngas fermentation.

The hybrid gasification-syngas fermentation platform can produce more bioethanol utilizing all biomass components compared to the biochemical conversion technology. Syngas fermentation operates at mild temperatures and pressures and avoids using expensive pretreatment processes and enzymes. This study presents a new process simulation model developed with Aspen Plus® of a biorefinery based on a hybrid conversion technology for the production of anhydrous ethanol using 1200tons per day (wb) of switchgrass. The simulation model consists of three modules: gasification, fermentation, and product recovery. The results revealed a potential production of about 36.5million gallons of anhydrous ethanol per year. Sensitivity analyses were also performed to investigate the effects of gasification and fermentation parameters that are keys for the development of an efficient process in terms of energy conservation and ethanol production.

Multiwalled Carbon Nanotubes at the Interface of Pickering Emulsions.

Carbon nanotubes exhibit very unique properties in biphasic systems. Their interparticle attraction leads to reduced droplet coalescence rates and corresponding improvements in emulsion stability. Here we use covalent and noncovalent techniques to modify the hydrophilicity of multiwalled carbon nanotubes (MWCNTs) and study their resulting behavior at an oil-water interface. By using both paraffin wax/water and dodecane/water systems, the thickness of the layer of MWNTs at the interface and resulting emulsion stability are shown to vary significantly with the approach used to modify the MWNTs. Increased hydrophilicity of the MWNTs shifts the emulsions from water-in-oil to oil-in-water. The stability of the emulsion is found to correlate with the thickness of nanotubes populating the oil-water interface and relative strength of the carbon nanotube network. The addition of a surfactant decreases the thickness of nanotubes at the interface and enhances the overall interfacial area stabilized at the expense of increased droplet coalescence rates. To the best of our knowledge, this is the first time the interfacial thickness of modified carbon nanotubes has been quantified and correlated to emulsion stability.

Life cycle assessment of the production of ethanol from eastern redcedar.

This life cycle assessment (LCA) evaluates the environmental impacts of an ethanol production system using eastern redcedar (Juniperus virginiana L.) as the feedstock. Aspen Plus® was used to model the acid bisulfite pretreatment, enzymatic hydrolysis, fermentation, and distillation steps. A cradle-to-gate LCA was conducted to evaluate the environmental impacts from cutting the trees to the production of anhydrous ethanol. The environmental impacts of the redcedar ethanol process were compared to those from the production of corn ethanol. Inventory data for the system were collected and used to calculate a life cycle impact assessment (LCIA) using the IMPACT 2002+ and BEES+ framework in SimaPro 8.0.0. Four impact categories were evaluated: land occupation, water use, greenhouse gas (GHG) emissions, and non-renewable energy use. Results indicate that acid bisulfite pretreatment contributed to 65% of GHG emissions, 81% of non-renewable energy use, and 77% of water use of the overall process.

Amine modeling for CO2 capture: internals selection.

Traditionally, trays have been the mass-transfer device of choice in amine absorption units. However, the need to process large volumes of flue gas to capture CO2 and the resultant high costs of multiple trains of large trayed columns have prompted process licensors and vendors to investigate alternative mass-transfer devices. These alternatives include third-generation random packings and structured packings. Nevertheless, clear-cut guidelines for selection of packings for amine units are lacking. This paper provides well-defined guidelines and a consistent framework for the choice of mass-transfer devices for amine absorbers and regenerators. This work emphasizes the role played by the flow parameter, a measure of column liquid loading and pressure, in the type of packing selected. In addition, this paper demonstrates the significant economic advantage of packings over trays in terms of capital costs (CAPEX) and operating costs (OPEX).

Water in oil emulsion droplet size characterization using a pulsed field gradient with diffusion editing (PFG-DE) NMR technique.

This paper describes a proton nuclear magnetic resonance (NMR) technique, pulsed field gradient with diffusion editing (PFG-DE), to quantify drop size distributions of brine/crude oil emulsions. The drop size distributions obtained from this technique were compared to results from the traditional pulsed field gradient (PFG) technique. The PFG-DE technique provides both transverse relaxation (T2) and drop size distributions simultaneously. In addition, the PFG-DE technique does not assume a form of the drop size distribution. An algorithm for the selection of the optimal parameters to use in a PFG-DE measurement is described in this paper. The PFG-DE technique is shown to have the ability to resolve drop size distributions when the T2 distribution of the emulsified brine overlaps either the crude oil or the bulk brine T2 distribution. Finally, the PFG-DE technique is shown to have the ability to resolve a bimodal drop size distribution.