Recombinant Spider Silk Hydrogels for Sustained Release of Biologicals.

Therapeutic biologics (i.e., proteins) have been widely recognized for the treatment, prevention, and cure of a variety of human diseases and syndromes. However, design of novel protein-delivery systems to achieve a nontoxic, constant, and efficient delivery with minimal doses of therapeutic biologics is still challenging. Here, recombinant spider silk-based materials are employed as a delivery system for the administration of therapeutic biologicals. Hydrogels made of the recombinant spider silk protein eADF4(C16) were used to encapsulate the model biologicals BSA, HRP, and LYS by direct loading or through diffusion, and their release was studied. Release of model biologicals from eADF4(C16) hydrogels is in part dependent on the electrostatic interaction between the biological and the recombinant spider silk protein variant used. In addition, tailoring the pore sizes of eADF4(C16) hydrogels strongly influenced the release kinetics. In a second approach, a particles-in-hydrogel system was used, showing a prolonged release in comparison with that of plain hydrogels (from days to week). The particle-enforced spider silk hydrogels are injectable and can be 3D printed. These initial studies indicate the potential of recombinant spider silk proteins to design novel injectable hydrogels that are suitable for delivering therapeutic biologics.

Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug.

Oral administration of low permeable drugs remains a challenge as they do not cross biological membrane efficiently and therefore exhibit a poor bioavailability. Herein, the effect of magnetic retention on the circulation and bioavailability of magnetic beads in the gastrointestinal tract in the presence of an external magnetic field is evaluated. Retention efficiency is imaged using magnetic resonance and near infrared techniques. The effect on bioavailability is then evaluated in a pharmacokinetic study. Iron oxide nanoparticles, the drug (dipeptidyl peptidase-IV inhibitor) and a fluorophore (Alexa Fluor-750) are co-encapsulated in chitosan-alginate core-shell beads. Retention of these beads is induced by the presence of an external permanent magnet on the abdomen of rats. After single administration of magnetic beads containing 20mg/kg of drug to fasted rats, a 2.5-fold increase in drug's bioavailability is observed in the presence of an external magnetic field, significantly higher than the same dose administered to rats without the field or for the drug in aqueous solution. Retention of the magnetic carriers in the presence of an external magnet proves to accumulate these carriers in a specific localization of the intestine leading to a significant improve in the drug's bioavailability.

Performance of magnetic chitosan-alginate core-shell beads for increasing the bioavailability of a low permeable drug.

This work reports the synthesis and performance of magnetic chitosan-alginate core-shell beads for oral administration of small molecules in order to increase their bioavailability. For this purpose, we designed magnetic core-shell beads suitable for oral delivery that are resistant in acidic media (stomach pH), mucoadhesive, exhibit a superparamagnetic behavior and a very high entrapment efficiency. Ex vivo experiments were performed in Ussing chambers, to emphasize the effect of magnetic accumulation. The amount of drug permeated through the membrane exhibited a threefold increase with our novel drug delivery system. According to a correlation law, our ex vivo model showed that the adsorbed fraction (FA) in human is expected to reach 70% when using the magnetic retention system which is a great improvement when compared to the controls (FA=20%).

Structure and mechanical properties of hydroxypropylated starch films.

Films of acid-hydrolyzed hydroxypropylated pea starch with average molecular weight M w ranging from 3.3 x 10 (4) g/mol to 1.6 x 10 (6) g/mol were prepared from 25% (w/w) solution by casting. The structure of the films was investigated by means X-ray diffraction and calorimetry, evidencing a B-type crystalline structure. In similar drying conditions, 25 degrees C and 40% of relative humidity, the crystallinity varied from 24% for the low molecular weight (A5) to almost none for the highest molecular weight (A160). The influence of the drying temperature was also investigated. A reduction of the crystallinity from 16% to almost none was found when increasing temperature from 25 to 65 degrees C. The glass transition temperature ( T g) at different water contents was determined. The difference of T g between the first and the second scan was interpreted by changes in the water distribution between phases into the B-type crystalline structure. Mechanical properties of the films determined by tensile tests and by DMTA in the glassy state showed no effect of the average molecular weight or of crystallinity. In contrast, thermomechanical experiments by DMTA showed that the average molecular weight of the sample influenced the mechanical relaxation and the moduli in the rubbery state.