Biphasic Porous Bijel-Like Structures with Hydrogel Domains as Controlled Drug Delivery Systems.

Bijels are a peculiar type of Pickering emulsion that have a bicontinuous morphology and are stabilised by a jammed layer of nanoparticles (NPs). Due to their double nature, their usage has increased in recent years in various fields, such as biological and food applications. In fact, they can release both hydrophilic and hydrophobic compounds simultaneously. An improvement to this structure is the use of a hydrophobic monomer like polycaprolactone as the organic phase, which is able to polymerise during the formation of the structure. Unfortunately, the structures formed in this way always have some drawbacks, such as their thermal stability or degradation when submerged in an aqueous medium. A number of studies have been carried out in which some parameters, such as the NPs or the monomer, were changed and their effect on the final product evaluated. In this work, the effect of modifying the aqueous phase was studied. In particular, the effect of adding alginate, a biopolymer capable of forming a stable hydrogel in the presence of divalent cations, was analysed, as was the difference between soaking or not in CaCl2, the final system. Specific attention was paid to their swelling behaviour (150% vs. 25% of the blank sample), rheological properties (G' 100 kPa vs. 20 kPa of the blank sample) and their release performances. In this framework, complete release of hydrophilic drug vs. 20% in the blank sample was observed together with improved release of the hydrophobic one with 35% in 8 h vs. 5% in the case of the blank sample. This strategy has been proven to influence bijels' properties, opening the doors to many different uses.

ß-Cyclodextrin functionalized agarose-based hydrogels for multiple controlled drug delivery of ibuprofen.

Agarose hydrogels are three-dimensional hydrophilic polymeric frameworks characterised by high water content, viscoelastic properties, and excellent ability as cell and drug delivery systems. However, their hydrophilicity as gel systems makes loading of hydrophobic drugs difficult and often ineffective. The incorporation of amphiphilic molecules (e.g. cyclodextrins) into hydrogels as hosts able to form inclusion complexes with hydrophobic drugs could be a possible solution. However, if not properly confined, the host compounds can get out of the network resulting in uncontrolled release. Therefore, in this work, ß-cyclodextrins-based host-guest supramolecular hydrogel systems were synthesised, with ß-cyclodextrins (ß-CD) covalently bound to the polymeric network, preventing leakage of the host molecules. Hydrogels were prepared at two different ß-CD-functionalized polyvinyl alcohol (PVA)/agarose ratios, and characterised chemically and physically. Then ibuprofen, a drug often used as a gold standard in studies involving ß-CD both in its hydrophilic and hydrophobic forms, was selected to investigate the release behavior of the synthesised hydrogels and the influence of ß-CD on the release. The presence of ß-CD linked to the polymeric 3D network ensured a higher and prolonged release profile for the hydrophobic drug and also seemed to have some influence on the hydrophilic one.

Bioinspired in vitro intestinal mucus model for 3D-dynamic culture of bacteria.

The intestinal mucus is a biological barrier that supports the intestinal microbiota growth and filters molecules. To perform these functions, mucus possesses optimized microstructure and viscoelastic properties and it is steadily replenished thus flowing along the gut. The available in vitro intestinal mucus models are useful tools in investigating the microbiota-human cells interaction, and are used as matrices for bacterial culture or as static component of microfluidic devices like gut-on-chips. The aim of this work is to engineer an in vitro mucus models (I-Bac3Gel) addressing in a single system physiological viscoelastic properties (i.e., 2-200 Pa), 3D structure and suitability for dynamic bacterial culture. Homogeneously crosslinked alginate hydrogels are optimized in composition to obtain target viscoelastic and microstructural properties. Then, rheological tests are exploited to assess a priori the hydrogels capability to withstand the flow dynamic condition. We experimentally assess the suitability of I-Bac3Gels in the evolving field of microfluidics by applying a dynamic flow to a bacterial-loaded mucus model and by monitoring E. coli growth and survival. The engineered models represent a step forward in the modelling of the mucus, since they can answer to different urgent needs such as a 3D structure, bioinspired properties and compatibility with dynamic system.