Gelation under stress: impact of shear flow on the formation and mechanical properties of methylcellulose hydrogels.

We demonstrate that small unidirectional applied-stresses during temperature-induced gelation dramatically change the gel temperature and the resulting mechanical properties and structure of aqueous methylcellulose (MC), a material that forms a brittle gel with a fibrillar microstructure at elevated temperatures. Applied stress makes gelation more difficult, evidenced by an increased gelation temperature, and weakens mechanical properties of the hot gel, evidenced by a decreased elastic modulus and decreased apparent failure stress. In extreme cases, formation of a fully percolated polymer network is inhibited and a soft granular yield-stress fluid is formed.

High throughput research and evaporation rate modeling for solvent screening for ethylcellulose barrier membranes in pharmaceutical applications.

Context: Ethylcellulose is commonly dissolved in a solvent or formed into an aqueous dispersion and sprayed onto various dosage forms to form a barrier membrane to provide controlled release in pharmaceutical formulations. Due to the variety of solvents utilized in the pharmaceutical industry and the importance solvent can play on film formation and film strength it is critical to understand how solvent can influence these parameters.

Objective: To systematically study a variety of solvent blends and how these solvent blends influence ethylcellulose film formation, physical and mechanical film properties and solution properties such as clarity and viscosity.

Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications.

The feasibility of various cellulose polymer derivatives, including methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), sodium-carboxymethylcellulose (sodium-CMC), and cationic-hydroxyethylcellulose (cationic-HEC), for use as an excipient to enhance drug delivery in nasal spray formulations was investigated. Three main parameters for evaluating the polymers in nasal drug delivery applications include rheology, ciliary beat frequency (CBF), and permeation across nasal tissue. Reversible thermally induced viscosity enhancement was observed at near nasal physiological temperature when cellulose derivatives were combined with an additional excipient, poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) graft copolymer (PVCL-PVA-PEG).

Identification of FAK substrate peptides via colorimetric screening of a one-bead one-peptide combinatorial library.

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is associated with regulating cellular functions such as cell adhesion and migration and has emerged as an important target for cancer research. Short peptide substrates that are selectively and efficiently phosphorylated by FAK have not been previously identified and tested. Here we report the synthesis and screening of a one-bead one-peptide combinatorial library to identify novel substrates for FAK.

Effect of formulation conditions on hypromellose performance properties in films used for capsules and tablet coatings.

This study investigated the effects of polymer dispersion and hydration conditions on hypromellose (HPMC) film properties, such as strength, oxygen permeability, water vapor transmission, clarity, and haze. The focus of the study was to build a better understanding of the impact that changes to HPMC dispersion and hydration conditions have on performance properties of the resulting films. This understanding could potentially lead to more flexible formulation guidelines for formulators.

Solid-state nuclear magnetic resonance (NMR) spectroscopy of human immunodeficiency virus gp41 protein that includes the fusion peptide: NMR detection of recombinant Fgp41 in inclusion bodies in whole bacterial cells and structural characterization of purified and membrane-associated Fgp41.

Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The 175 N-terminal residues make up the ectodomain that lies outside the virus. This work describes the production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues, including the fusion peptide (FP) that binds to target cell membranes.

Native conformation at specific residues in recombinant inclusion body protein in whole cells determined with solid-state NMR spectroscopy.

Inclusion bodies are insoluble aggregates that are formed by bacteria to store excess recombinant protein produced during expression. The structure of the protein in inclusion bodies is poorly understood but it has been hypothesized that the protein may form misfolded beta sheet aggregates. This paper presents an isotopic labeling and solid-state nuclear magnetic resonance approach to determine the secondary structure of individual residues within a recombinant influenza virus "FHA2" protein in inclusion bodies.

Isotopically labeled expression in E. coli, purification, and refolding of the full ectodomain of the influenza virus membrane fusion protein.

This paper describes methods to produce an isotopically labeled 23 kDa viral membrane protein with purified yield of 20 mg/L of Escherichia coli shake flask culture. This yield is sufficient for NMR structural studies and the protein production methods are simple, straightforward, and rapid and likely applicable to other recombinant membrane proteins expressed in E. coli.