Supercritical Fluid-Assisted Decoration of Nanoparticles on Porous Microcontainers for Codelivery of Therapeutics and Inhalation Therapy of Diabetes.

The impact of nanotechnology and its advancements have allowed us to explore new therapeutic modalities. To this end, we designed nanoparticles-inlaid porous microparticles (NIPMs) coloaded with small interfering RNA (siRNA) and glucagon-like peptide-1 (GLP-1) using the supercritical carbon dioxide (SC-CO2) technology as an inhalation delivery system for diabetes therapy. siRNA-encapsulating chitosan (CS) nanoparticles were first synthesized by an ionic gelation method, which resulted in particles with small sizes (100-150 nm), high encapsulation efficiency (∼94.8%), and sustained release performance (∼60% in 32 h). These CS nanoparticles were then loaded with GLP-1-dispersed poly-l-lactide (PLLA) porous microparticles (PMs) by SC-CO2-assisted precipitation with the compressed antisolvent (PCA) process. The hypoglycemic efficacy of NIPMs administered via pulmonary route in mice persisted longer due to sustained release of siRNA from CS nanoparticles and the synergistic effects of GLP-1 in PMs, which significantly inhibited the expression of dipeptidyl peptidase-4 mRNA (DPP-4-mRNA). This ecofriendly technology provides a convenient way to fabricate nanoparticle-microparticle composites for codelivery of a gene and a therapeutic peptide, which will potentially find widespread applications in the field of pharmaceutics.

Preparation of Chitosan-Based Hemostatic Sponges by Supercritical Fluid Technology.

Using ammonium bicarbonate (AB) particles as a porogen, chitosan (CS)-based hemostatic porous sponges were prepared in supercritical carbon dioxide due to its low viscosity, small surface tension, and good compatibility with organic solvent. Fourier transform infrared spectroscopy (FTIR) spectra demonstrated that the chemical compositions of CS and poly-(methyl vinyl ether-co-maleic anhydride) (PVM/MA) were not altered during the phase inversion process. The morphology and structure of the sponge after the supercritical fluid (SCF) process were observed by scanning electron microscopy (SEM). The resulting hemostatic sponges showed a relatively high porosity (about 80%) with a controllable pore size ranging from 0.1 to 200 µm. The concentration of PVM/MA had no significant influence on the porosity of the sponges. Comparative experiments on biological assessment and hemostatic effect between the resulting sponges and Avitene® were also carried out. With the incorporation of PVM/MA into the CS-based sponges, the water absorption rate of the sponges increased significantly, and the CS-PVM/MA sponges showed a similar water absorption rate (about 90%) to that of Avitene®. The results of the whole blood clotting experiment and animal experiment also demonstrated that the clotting ability of the CS-PVM/MA sponges was similar to that of Avitene®. All these results elementarily verified that the sponges prepared in this study were suitable for hemostasis and demonstrated the feasibility of using SCF-assisted phase inversion technology to produce hemostatic porous sponges.