pO2 reporter composite hydrogel macroencapsulation devices for magnetic resonance imaging oxygen quantification.

Hydrogel cell encapsulation devices are a common approach to reduce the need for chronic systemic immunosuppression in allogeneic cell product transplantation. Macroencapsulation approaches are an appealing strategy, as they maximize graft retrievability and cell dosage within a single device; however, macroencapsulation devices face oxygen transport challenges as geometries increase from preclinical to clinical scales. Device design guided by computational approaches can facilitate graft oxygen availability to encapsulated cells in vivo but is limited without accurate measurement of oxygen levels within the transplant site and graft. In this study, we engineer pO2 reporter composite hydrogels (PORCH) to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the proton Imaging of siloxanes to map tissue oxygenation levels (PISTOL) magnetic resonance imaging approach. We engineer two methods of incorporating siloxane oximetry reporters within hydrogel devices, an emulsion and microbead-based approach, and evaluate PORCH cytotoxicity on co-encapsulated cells and accuracy in quantifying oxygen tension in vitro. We find that both emulsion and microbead PORCH approaches enable accurate in situ oxygen quantification using PISTOL magnetic resonance oximetry, and that the emulsion-based PORCH approach results in higher spatial resolution.

Evaluation of the physicochemical characteristics of crospovidone that influence solid dispersion preparation.

A solid dispersion (SD) powder of indomethacin (IM) with crospovidone (CrosPVP) shows useful characteristics for manufacturing dosage forms. Four types of commercial CroPVP, Polyplasdone XL (XL) used as the initial carrier, Polyplasdone XL10 and INF-10 manufactured by milling XL, and Kollidon CL (CL) marketed by another company, were compared. The limit of the IM-CrosPVP weight ratio with which an SD can be prepared (maximum IM content) was calculated on the basis of the heat of fusion of physical mixtures of IM and CrosPVP with various weight ratios. When Polyplasdones were used, the maximum IM content increased with the specific surface area of the CrosPVP. When CL was used, however, it was about half of that obtained with XL, even though the difference between XL and CL was not observed in the physicochemical characteristics (particle size, specific surface area, flowability, glass transition temperature, IR spectra, and solid state NMR spectra). As determined by pore size distribution measurement, the volume of pore of which size is larger than the particle size of IM was less in CL than in XL. Therefore, the effective surface area of CrosPVP that comes in contact with IM is important for the preparation of the SD.

Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone.

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 µm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds.

The preparation of a solid dispersion powder of indomethacin with crospovidone using a twin-screw extruder or kneader.

A solid dispersion (SD) powder of indomethacin (IM) with CrosPVP was prepared continuously using a twin-screw extruder (extruder) or twin-screw kneader (kneader), which made it possible to simultaneously control kneading, mixing, and heating. For the extruder or kneader, IM existed in an amorphous state while it was treated with a screw rotation speed of 15 min(-1) or 50 min(-1), respectively, while being heated to 140 degrees C. IM and CrosPVP interacted to maintain IM in an amorphous state. The solubility of SD powders of IM was improved about four-fold compared to crystalline IM. The retention time of the samples in the machine, screw rotation speed, and heating temperature play important roles in the preparation of SD. Although SD was prepared using a theta composer followed by heating at 125 degrees C for 30 min, it is more useful to be able to continuously prepare powdered SD by heating below the melting point (140 degrees C) in a short time (4 min) using an extruder or a kneader from the viewpoint of manufacturing.