RESUMO
The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, "simplex centroid mixture design," was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the gel formed at 37 °C upon dilution in SCF. The optimized vehicle was loaded with maqui berry extract (MBE), known for its antioxidant and anti-inflammatory properties. MBE loading (0.5% w/w) into the vehicle improved rheological and mucoadhesive properties of the formulation. Both MBE and the optimized vehicle were not cytotoxic towards human fibroblasts and Caco-2 cells. Moreover, the optimized vehicle did not affect MBE antioxidant properties.
RESUMO
In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and re-epithelialization. The aim of this work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds: as component of the PUL/SA matrix, to be electrospun, or as coating component, to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration, to obtain electrospun nanofibers, has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and these were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofiber morphology before crosslinking, while the crosslinking process, in presence of PL, determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary, the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially for PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular, fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblast-to-myofibroblast transition that could enhance wound healing.