How strongly does trehalose interact with lysozyme in the solid state? Insights from molecular dynamics simulation and inelastic neutron scattering.

Therapeutic proteins are usually conserved in glassy matrixes composed of stabilizing excipients and a small amount of water, which both control their long-term stability, and thus their potential use in medical treatments. To shed some light on the protein-matrix interactions in such systems, we performed molecular dynamics (MD) simulations on matrixes of (i) the model globular protein lysozyme (L), (ii) the well-known bioprotectant trehalose (T), and (iii) the 1:1 (in weight) lysozyme/trehalose mixture (LT), at hydration levels h of 0.0, 0.

Predictability of drug release from cochlear implants.

A simplified mathematical theory is presented allowing for in silico simulation of the effects of key parameters of miniaturized implants (size and composition) on the resulting drug release kinetics. Such devices offer a great potential, especially for local drug treatments, e.g.

Non-coated multiparticulate matrix systems for colon targeting.

Background: Colon specific drug delivery can significantly improve the efficacy of local treatments of inflammatory bowel diseases. Film coatings containing the starch derivative Nutriose have recently been reported to minimize 5-ASA release in media simulating the upper gastro intestinal tract (GIT), while releasing the drug in a time-controlled manner upon contact with feces from Crohn's Disease and Ulcerative Colitis patients. It was the aim of this study to prepare Nutriose-containing matrix pellets and mini tablets in order to avoid a film coating step.

Influence of urea and guanidine hydrochloride on lysozyme stability and thermal denaturation; a correlation between activity, protein dynamics and conformational changes.

The effect of urea and guanidine hydrochloride (GuHCl) on lysozyme stability has been investigated using activity measurements, microcalorimetry and Raman spectroscopy in the low-frequency and amide I regions. Raman investigations on lysozyme dissolved in H(2)O and D(2)O in the presence of up to 10 M denaturants have revealed direct binding between the protein and both denaturants. The analysis of isotopic exchanges in the amide I region allows the identification of binding sites as hydrophilic and hydrophobic groups, respectively, for urea and GuHCl.

How porosity and size affect the drug release mechanisms from PLGA-based microparticles.

Porous, poly(lactic-co-glycolic acid) (PLGA)-based microparticles were prepared using a water-in-oil-in-water (W/O/W) solvent extraction/evaporation technique. Lidocaine was used as a model drug and different-sized particle fractions were obtained by sieving. The physicochemical properties of the devices and changes thereof upon exposure to phosphate buffer pH 7.