An In Situ Gelling System for the Local Treatment of Inflammatory Bowel Disease (IBD). The Loading of Maqui (Aristotelia chilensis) Berry Extract as an Antioxidant and Anti-Inflammatory Agent

Abstract

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.

Native Chilean Berries Preservation and In Vitro Studies of a Polyphenol Highly Antioxidant Extract from Maqui as a Potential Agent against Inflammatory Diseases

“…For example, pre-incubation of fibroblast and Caco-2 cells with anthocyanin rich maqui berry extract has shown a protective effect against OS along with a high capacity to inhibit human low-density lipoprotein (LDL) oxidation [28]. Additionally, the maqui extract exhibits an important anti-inflammatory effect in RAW 264.7 macrophages cells [29] by inhibition of gene expression of iNOS, COX-2, TNF-α, IL-6, and IL-10 [24,30].…”

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

“…An innovative in situ gelling system to be applied on the mucosa of the distal colon via rectal route was recently developed by our group [ 7 ]. The system was based on three polymers having different functions such as GG, polymer capable of gelling in presence of ions, MC, polymer characterized by a gelation temperature close to 50 °C, and HPC, polymer capable to interact with mucin/mucosa.…”

“…It is well-known that some anionic polysaccharides (alginate (ALG), gellan gum (GG) and pectin (PEC)) are ion-sensitive polymers [ 5 , 6 , 7 , 8 , 9 ]; they are cross-linked by some monovalent (Na + ) and/or divalent (Mg 2+ and Ca 2+ ) cations present in different physiological fluids, such as saliva, tears, nasal fluid, etc. The cross-link mechanism produces a sol–gel transition, with the formation of a strong gel.…”

Gellan-Based Composite System as a Potential Tool for the Treatment of Nervous Tissue Injuries: Cross-Linked Electrospun Nanofibers Embedded in a RC-33-Loaded Freeze-Dried Matrix

“…In recent years, gellan gum (GG) has become an attractive biomaterial for regenerative medicine purposes due to its hydrogel-forming properties when combined with some monovalent (Na + ) and/or divalent (Mg 2+ and Ca 2+ ) cations present in physiological fluids [ 15 , 16 , 17 ]. GG is an exocellular polysaccharide produced by Sphingomonas elodea bacteria, characterized by a linear anionic structure composed of repeated tetrasaccharide units (1,3-β- d -glucose, 1,4-β- d -glucuronic acid, 1,4-β- d -glucose and 1,4-α- l -rhamnose).…”