Photoinitiated chemical vapor deposition of cytocompatible poly(2-hydroxyethyl methacrylate) films.

Poly(2-hydroxyethyl methacrylate) (pHEMA) is a widely utilized biomaterial due to lack of toxicity and suitable mechanical properties; conformal thin pHEMA films produced via chemical vapor deposition (CVD) would thus have broad biomedical applications. Thin films of pHEMA were deposited using photoinitiated CVD (piCVD). Incorporation of ethylene glycol diacrylate (EGDA) into the pHEMA polymer film as a crosslinker, confirmed via Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, resulted in varied swelling and degradation behavior.

Model predicting impact of complexation with cyclodextrins on oral absorption.

Significant effort and resource expenditure is dedicated to enabling low-solubility oral drug delivery using solubilization technologies. Cyclodextrins (CD) are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. It is not clear prior to developing a drug delivery device with CD what level of absorption enhancement might be achieved; modeling can provide useful guidance in formulation and minimize resource intensive iterative formulation development.

Generation of tissue constructs for cardiovascular regenerative medicine: from cell procurement to scaffold design.

The ability of the human body to naturally recover from coronary heart disease is limited because cardiac cells are terminally differentiated, have low proliferation rates, and low turn-over rates. Cardiovascular tissue engineering offers the potential for production of cardiac tissue ex vivo, but is currently limited by several challenges: (i) Tissue engineering constructs require pure populations of seed cells, (ii) Fabrication of 3-D geometrical structures with features of the same length scales that exist in native tissue is non-trivial, and (iii) Cells require stimulation from the appropriate biological, electrical and mechanical factors. In this review, we summarize the current state of microfluidic techniques for enrichment of subpopulations of cells required for cardiovascular tissue engineering, which offer unique advantages over traditional plating and FACS/MACS-based enrichment.

Modeling the human intestinal mucin (MUC2) C-terminal cystine knot dimer.

Intestinal mucus, a viscous secretion that lines the mucosa, is believed to be a barrier to absorption of many therapeutic compounds and carriers, and is known to play an important physiological role in controlling pathogen invasion. Nevertheless, there is as yet no clear understanding of the barrier properties of mucus, such as the nature of the molecular interactions between drug molecules and mucus components as well as those that govern gel formation. Secretory mucins, large and complex glycoprotein molecules, are the principal determinants of the viscoelastic properties of intestinal mucus.

Predicting the effect of fed-state intestinal contents on drug dissolution.

Purpose: There are several endogenous and exogenous species in the gastrointestinal (GI) tract which can act as solubilizing agents and thereby affect drug dissolution. The purpose of this study is to understand food effects on drug dissolution and provide insight into their anticipated overall effect on absorption and bioavailability.

Methods: Dissolution kinetics of 15 drugs of variable logP, charge, and molecular weight were tested in simulated intestinal environment.

Drug salts and solubilization: modeling the influence of cyclodextrins on oral absorption.

Substantial effort and resources are spent for the oral delivery of low solubility compounds using drug delivery technologies. Complexation using cyclodextrins (CDs) is one popular strategy used to enhance drug dissolution kinetics and solubility. In addition to delivery technologies, another common method of improving dissolution kinetics of a low solubility compound is to dose it as a salt.

Barrier properties of gastrointestinal mucus to nanoparticle transport.

Gastrointestinal mucus, a complex network of highly branched glycoproteins and macromolecules, is the first barrier through which orally delivered drug and gene vectors must traverse. The diffusion of such vectors can be restricted by the high adhesivity and viscoelasticity of mucus. In this investigation, the barrier properties of gastrointestinal mucus to particle transport were explored using real-time multiple particle tracking.

Shotgun proteomic analysis of yeast-elicited California poppy (Eschscholzia californica) suspension cultures producing enhanced levels of benzophenanthridine alkaloids.

The California poppy, Eschscholzia californica, produces benzophenanthridine alkaloids (BPAs), an important class of biologically active compounds. Cell cultures of E. californica were investigated as an alternative and scalable method for producing these valuable compounds; treatment with yeast extract increased production from low levels to 23 mg/g dry weight (DW) of BPAs.

A model predicting delivery of saquinavir in nanoparticles to human monocyte/macrophage (Mo/Mac) cells.

Modeling the influence of a technology such as nanoparticle systems on drug delivery is beneficial in rational formulation design. While there are many studies showing drug delivery enhancement by nanoparticles, the literature provides little guidance regarding when nanoparticles are useful for delivery of a given drug. A model was developed predicting intracellular drug concentration in cultured cells dosed with nanoparticles.

Flow characterization of a wavy-walled bioreactor for cartilage tissue engineering.

Cartilage tissue engineering requires the use of bioreactors in order to enhance nutrient transport and to provide sufficient mechanical stimuli to promote extracellular matrix (ECM) synthesis by chondrocytes. The amount and quality of ECM components is a large determinant of the biochemical and mechanical properties of engineered cartilage constructs. Mechanical forces created by the hydrodynamic environment within the bioreactors are known to influence ECM synthesis.

Precursor limitations in methyl jasmonate-induced Catharanthus roseus cell cultures.

Jasmonates enhance the expression of various genes involved in terpenoid indole alkaloid (TIA) biosynthesis in Catharanthus roseus. We applied precursor feeding to our C. roseus suspensions to determine how methyl jasmonate (MJ) alters the precursor availability for TIA biosynthesis.

Ajmalicine production in methyl jasmonate-induced Catharanthus roseus cell cultures depends on Ca2+ level.

Cytosolic Ca(2+) and jasmonate mediate signals that induce defense responses in plants. In this study, the interaction between Ca(2+) and methyl jasmonate (MJ) in modulating defense responses was investigated by monitoring ajmalicine production in Catharanthus roseus suspension cultures. C.

Enhancement of ajmalicine production in Catharanthus roseus cell cultures with methyl jasmonate is dependent on timing and dosage of elicitation.

The optimum growth stage for enhancing ajmalicine production in Catharanthus roseus cultures with methyl jasmonate (MJ) was after 6 d growth. MJ added at 10 or 100 microm on day 6 gave a maximum ajmalicine production of 10.2 mg l(-1), a 300% increase over that of non-elicited cultures.

Increased rate of chondrocyte aggregation in a wavy-walled bioreactor.

A novel wavy-walled bioreactor designed to enhance mixing at controlled shear stress levels was used to culture chondrocytes in suspension. Chondrocyte aggregation in suspensions mixed at 30, 50, and 80 rpm was characterized in the wavy-walled bioreactor and compared with that in conventional smooth-walled and baffled-walled spinner flask bioreactors. Aggregation was characterized in terms of the percentage of cells that aggregated over time, and aggregate size changes over time.