This work explores the potential of polymeric micrometer sized devices (microcontainers) as oral drug delivery systems (DDS). Arrays of detachable microcontainers (D-MCs) were fabricated on a sacrificial layer to improve the handling and facilitate the collection of individual D-MCs. A model drug, ketoprofen, was loaded into the microcontainers using supercritical CO impregnation, followed by deposition of an enteric coating to protect the drug from the harsh gastric environment and to provide a fast release in the intestine. In vitro, in vivo and ex vivo studies were performed to assess the viability of the D-MCs as oral DDS. D-MCs improved the relative oral bioavailability by 180% within 4h, and increased the absorption rate by 2.4 times compared to the control. This work represents a significant step forward in the translation of these devices from laboratory to clinic.

Tissue damage caused by excessive amounts of neutrophil-derived reactive oxygen species (ROS) occurs in many inflammatory diseases. Butyrate is a short-chain fatty acid (SCFA) with known anti-inflammatory properties, able to modulate several neutrophil functions. Evidence is provided here that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear as promising tools to limit ROS-dependent tissue injury during inflammation. Particularly, by virtue of their mucoadhesiveness, B-NPs administered by enema can be effective in the treatment of inflammatory bowel diseases.

Thermosensitive hydrogels based on chitosan/pectin (CS/Pec) and CS/Pec/gold nanoparticles (CS/Pec/AuNPs) were successfully prepared with different AuNP levels. Using a tilting method, gelation temperature was demonstrated to decrease when the amount of AuNPs increased and pectin concentrations decreased. The presence of AuNPs in the CS/Pec composite was evaluated via WAXS and UV-vis techniques, while SEM analysis assessed the average size of pores (350-600μm). All samples were extremely cytocompatible with many cell types, such as normal kidney epithelial cells (VERO cells), epithelial colorectal adenocarcinoma cells (HT-29 cells), HPV-16 positive human cervical tumour cells (SiHa cells), kidney epithelial cells (LLCMK cells) and murine macrophage cells (J774A1 cells). Cell viability assays using the MTT method upon mouse preosteoblastic cells (MC3T3-E1 cells) showed that CS/Pec and CS/Pec/AuNPs composites had the potential to foster proliferation and growth of bone cells, making them possible stimulators for reconstruction of bone tissues.