A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson's disease.

Apomorphine, a dopamine agonist, is a highly effective therapeutic to prevent intermittent off episodes in advanced Parkinson's disease. However, its short systemic half-life necessitates three injections per day. Such a frequent dosing regimen imposes a significant compliance challenge, especially given the nature of the disease.

Topical treatment of periodontitis using an iongel.

Almost 50 % of the U.S. population suffers from oral infections such as periodontitis.

Ionic Liquid-Enabled Topical Delivery of Immunomodulators.

Skin is one of the most immunologically active organs of the body due to the presence of diverse immune cells and its active involvement in the innate and adaptive immunity. Because of its unique location and immunological role, skin offers an excellent site for the introduction of immunomodulators to synergize with the active immune microenviroment for the desired outcome. However, delivery of immunomodulators to the skin remains a significant challenge due to the skin's barrier properties.

Percutaneous liquid ablation agent for tumor treatment and drug delivery.

Percutaneous locoregional therapies (LRTs), such as thermal ablation, are performed to limit the progression of hepatocellular carcinoma (HCC) and offer a bridge for patients waiting for liver transplantation. However, physiological challenges related to tumor location, size, and existence of multiple lesions as well as safety concerns related to potential thermal injury to adjacent tissues may preclude the use of thermal ablation or lead to its failure. Here, we showed a successful injection of an ionic liquid into tissue under image guidance, ablation of tumors in response to the injected ionic liquid, and persistence (28 days) of coinjected chemotherapy with the ionic liquid in the ablation zone.

Investigating the potential use of an ionic liquid (1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide) as an anti-fungal treatment against the amphibian chytrid fungus, Batrachochytrium dendrobatidis.

The disease chytridiomycosis, caused by the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), has contributed to global amphibian declines. Bd infects the keratinized epidermal tissue in amphibians and causes hyperkeratosis and excessive skin shedding. In individuals of susceptible species, the regulatory function of the amphibian's skin is disrupted resulting in an electrolyte depletion, osmotic imbalance, and eventually death.

Oral ionic liquid for the treatment of diet-induced obesity.

More than 70% of American adults are overweight or obese, a precondition leading to chronic diseases, including diabetes and hypertension. Among other factors, diets with high fat and carbohydrate content have been implicated in obesity. In this study, we hypothesize that the choline and geranate (CAGE) ionic liquid can reduce body weight by decreasing fat absorption through the intestine.

A general approach for predicting protein epitopes targeted by antibody repertoires using whole proteomes.

Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing.

The Influence of Water on Choline-Based Ionic Liquids.

Choline and geranic acid (CAGE)-based ionic liquids have been recently developed for applications in drug delivery. Understanding the microscopic structures of CAGE in the presence of water is critical for its continued use in biomedical applications as it will undoubtedly come into contact with water in physiological fluids. Water can drastically impact the physicochemical properties of the ionic liquids, including CAGE.

Transdermal insulin delivery using choline-based ionic liquids (CAGE).

Transdermal delivery of pharmaceuticals using ionic liquids and deep eutectic solvents (DES) has attracted significant interest due to the inherent tunability of the molecules and their capacity to transport large molecules across the skin. Several key properties of DESs including viscosity, miscibility and possible transport enhancement can be controlled through the choice of ions and their ratio in DES. Herein we investigate the effect of cation/anion ratio using Choline and Geranic acid (CAGE) based DES.

Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE).

The continued emergence of antibiotic-resistant organisms has severely depleted our arsenal of effective antimicrobials. Ionic liquids (ILs) show great promise as antibacterial agents but understanding the mechanism of attack on bacterial cells is key to ensuring that design of IL-based biocides impart maximum efficacy with minimal toxicity, while also avoiding the potential for the target organisms to become resistant. Here we report the antibacterial attributes of a set of choline and geranate (CAGE)-based ILs and identify the mechanism by which they interact with the Gram-negative cell wall of .

Ionic liquids for oral insulin delivery.

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid.

Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial, temporal and concentration control.

Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages.

Ionic liquids for addressing unmet needs in healthcare.

Advances in the field of ionic liquids have opened new applications beyond their traditional use as solvents into other fields especially healthcare. The broad chemical space, rich with structurally diverse ions, and coupled with the flexibility to form complementary ion pairs enables task-specific optimization at the molecular level to design ionic liquids for envisioned functions. Consequently, ionic liquids now are tailored as innovative solutions to address many problems in medicine.

Prediction of antibody structural epitopes via random peptide library screening and next generation sequencing.

Next generation sequencing (NGS) is widely applied in immunological research, but has yet to become common in antibody epitope mapping. A method utilizing a 12-mer random peptide library expressed in bacteria coupled with magnetic-based cell sorting and NGS correctly identified >75% of epitope residues on the antigens of two monoclonal antibodies (trastuzumab and bevacizumab). PepSurf, a web-based computational method designed for structural epitope mapping was utilized to compare peptides in libraries enriched for monoclonal antibody (mAb) binders to antigen surfaces (HER2 and VEGF-A).

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent.

Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa).

Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing.

Disease-specific antibodies can serve as highly effective biomarkers but have been identified for only a relatively small number of autoimmune diseases. A method was developed to identify disease-specific binding motifs through integration of bacterial display peptide library screening, next-generation sequencing (NGS) and computational analysis. Antibody specificity repertoires were determined by identifying bound peptide library members for each specimen using cell sorting and performing NGS.

Longitudinal changes in blood pressure during weight loss and regain of weight in obese boys and girls.

Objective: To investigate blood pressure (BP) in relation to changes in body mass index (BMI) in obese children during weight loss and subsequent weight regain.

Design: A longitudinal study of obese boys and girls investigated through a 12-week weight loss intervention with follow-up investigations spanning 28 months. Results shown are from baseline; day 14, 33, and 82 during weight loss; and at months 10, 16 and 28 during follow-up.

Longitudinal analysis of leptin variation during weight regain after weight loss in obese children.

Objective: This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control.

Methods: 115 children were investigated during a 12-week weight loss program. 90 children completed the program, and 68 children entered a follow-up program spanning 28 months.

An economic comparison of different fermentation configurations to convert corn stover to ethanol using Z. mobilis and Saccharomyces.

Numerous routes are being explored to lower the cost of cellulosic ethanol production and enable large-scale production. One critical area is the development of robust cofermentative organisms to convert the multiple, mixed sugars found in biomass feedstocks to ethanol at high yields and titers without the need for processing to remove inhibitors. Until such microorganisms are commercialized, the challenge is to design processes that exploit the current microorganisms' strengths.

Contaminant occurrence, identification and control in a pilot-scale corn fiber to ethanol conversion process.

While interest in bioethanol production from lignocellulosic feedstocks is increasing, there is still relatively little pilot-plant data and operating experience available for this emerging industry. A series of batch and continuous fermentation runs were performed in a pilot-plant, some lasting up to six weeks, in which corn fiber-derived sugars were fermented to ethanol using glucose-fermenting and recombinant glucose/xylose-fermenting yeasts. However, contamination by Lactobacillus bacteria was a common occurrence during these runs.

A process economic approach to develop a dilute-acid cellulose hydrolysis process to produce ethanol from biomass.

Successful deployment of a bioethanol process depends on the integration of technologies that can be economically commercialized. Pretreatment and fermentation operations of the traditional enzymatic bioethanol-production process constitute the largest portion of the capital and operating costs. Cost reduction in these areas, through improved reactions and reduced capital, will improve the economic feasibility of a large-scale plant.

Conversion of distiller's grain into fuel alcohol and a higher-value animal feed by dilute-acid pretreatment.

Over the past three decades ethanol production in the United States has increased more than 10-fold, to approx 2.9 billion gal/yr (mid-2003), with ethanol production expected to reach 5 billion gal/yr by 2005. The simultaneous coproduction of 7 million t/yr of distiller's grain (DG) may potentially drive down the price of DG as a cattle feed supplement.

A bioethanol process development unit: initial operating experiences and results with a corn fiber feedstock.

Interest in bioethanol production from lignocellulosic feedstocks for use as an alternative fuel is increasing, but near-term commercialization will require a low cost feedstock. One such feedstock, corn fiber, was tested in the US Department of Energy (DOE)/National Renewable Energy Laboratory (NREL) bioethanol pilot plant for the purpose of testing integrated equipment operation and generating performance data. During initial runs in 1995, the plant was operated for two runs lasting 10 and 15 days each and utilized unit operations for feedstock handling, pretreatment by dilute sulfuric-acid hydrolysis, yeast inoculum production, and simultaneous saccharification and fermentation using a commercially available cellulase enzyme.