Oromucosal precursors of in loco hydrogels for wound-dressing and drug delivery in oral mucositis: Retain, resist, and release.

Oromucosal films and tablets were developed as multifunctional biomaterials for the treatment of oral mucositis. These are intended to function as a hybrid, performing as a controlled drug delivery system and as a wound-dressing device. The dosage forms are precursors for in loco hydrogels that are activated by the saliva. An anti-inflammatory and anesthetic activity is attained from budesonide tripartite polymeric nanoparticles and lidocaine, while the polymeric network allows the protection and cicatrization of the wound. Different biomaterials and blends were investigated, focusing on the capacity to retain and resist on-site, as well as achieve a long-lasting controlled release. As the limiting factor, the choice was made according to the films' results. A polymer mix of Methocel™ K100M and Carbopol® (974P, EDT 2020, or Ultrez 10) blends were used. Overall, regrading critical factors, Carbopol® increased films' elasticity and flexibility, mucoadhesion, and the strength of the hydrogels, while higher concentrations led to thicker, more opaque, and lower strain resistance products. Whereas 974P and Ultrez 10 performed similarly, EDT 2020 led to uniformity problems and weaker films, hydrogels and bioadhesion. The optimized products were enhanced with sodium hyaluronate and drug-loaded for further characterization. Concerning the dosage form, the films' hydrogels were more resilient, while the tablets had higher mucoadhesiveness and longer swelling. Although through different networks and mechanisms, both dosage forms and grades revealed similar release profiles. A Case II time-evolving stereoselectivity for the 22R and 22S budesonide epimers was found, and Fickian-diffusion for lidocaine. Ultimately, the developed formulations show great potential to be used in OM management. Both of the selected grades at 0.6% displayed excellent performance, while Ultrez 10 can be preferable for the films' production due to its lower viscosity before neutralization and higher after activation. Where the tablets are easier to produce and offer better adhesion, the films are more customizable post-production and have higher rheological performance for wound-dressing.