New tools to design smart thermosensitive hydrogels for protein rectal delivery in IBD.

Local treatment of Inflammatory Bowel Disease (IBD) has been pointed out to be a novel therapeutic approach with several advantages when compared to conventional therapies. However, the development of systems able to fulfil the requirements of this administration route is not an easy task. The present work suggests the utilization of Artificial Intelligence Tools (AIT) as an instrument to understand polymer-polymer interactions towards obtaining thermosensitive hydrogels suitable for protein rectal administration in IBD. Enemas composed by Pluronic® F127 and F68 and Methocel® K4M were developed and characterised. Two experimental designs were carried out in order to determine the effect of each polymer on their texturometric and rheological behaviour. Using the results of the first experimental design we can justify the inclusion of each raw material PF127, PF68 and MK4M in the formulation and conclude that a compromise solution is necessary to obtain thermosensitive hydrogels of the required properties. The results of the second experimental design allowed concluding that PF127 ruled mainly syringeability and bioadhesion work. On the other hand, PF68 modulated principally gelation temperature, viscosity and protein release from hydrogel matrix. Finally, MK4M influenced bioadhesiveness and mostly determined viscosity. AIT also allowed delimiting the design space to produce easy administrable and highly bioadhesive enemas that undergo fast sol-gel transitions at body temperature.