The effects of the molecular weight of chitosan on the tissue inflammatory response

Abstract

The molecular weight of chitosan (CS) may affect its physical properties and its ability to induce an appropriate host response. The biocompatibilities of CS membranes of low (LMWCS) and high (HMWCS) molecular weight were investigated by inserting these materials into the subcutaneous tissue of rats for 1-28 days and evaluating leukocyte infiltration, granulation tissue, fibrosis, arginase-1 immunostaining, as well as nuclear factor-κB (NF-κΒ) and fibroblast growth factor (FGF)-2 expressions. Both CS membranes induced a peak of leukocyte infiltration on the first day of insertion and stimulated granulation and fibrous tissue generation when compared to control.LMWCS induced more collagen deposition a week earlier, when compared to the control and HMWCS membrane. The membranes also increased arginase-1 immunostaining, a M2 macrophage marker. M2 macrophage is recognized as anti-inflammatory and pro-regenerative. NF-κB is an essential biomarker of the inflammatory process and induces the expression of several pro-inflammatory cytokines. The LMWCS membrane reduced inflammation, as indicated by a reduced nucleus/cytoplasm NF-κB ratio in surrounding tissue from days 7 to 14 when compared to control. On the first day, the expression of FGF-2, a biomarker of inflammatory resolution, was increased in the tissue of the LWMCS group, when compared with HMWCS, which was consistent with the type I collagen deposition. Thus, LWMCS was associated with a prior reduction of the inflammatory response and improved wound healing.

Preparation and Characterization of a Novel Multiparticulate Dosage Form Carrying Budesonide-Loaded Chitosan Nanoparticles to Enhance the Efficiency of Pellets in the Colon

“…The anti-inflammatory effect of chitosan against IBD and UC has been reported in previous studies [ 59 ] where high-molecular-weight chitosan had better therapeutic effects in UC compared with-low molecular-weight chitosan [ 60 ]. On the other hand, an increase in the molecular weight of chitosan could result in a decline in the drug release which could be due to the greater viscosity of the gel layer created around the drug particles upon contact with the dissolution medium [ 61 , 62 ].…”

“…Overall, results from the in vivo studies demonstrated that all prescribed formulations significantly are effective in colitis treatment. A decrease in inflammation in CN-treated rats could be related to the anti-inflammatory effects of chitosan in IBD [ 59 ].…”

Physicochemical Characterization and Immunomodulatory Activity of Polyelectrolyte Multilayer Coatings Incorporating an Exopolysaccharide from Bifidobacterium longum

“…It also seems that the rather pro- or anti-inflammatory action of chitosan is highly dependent on its molecular weight, preparation method, and the previous stimuli to which the cells were exposed . When implanted in rats, chitosan membranes with a lower molecular weight showed a reduced inflammatory response compared to higher molecular weight membranes . The chitosan used in the polyelectrolyte coatings may therefore contribute, at least partially, to the elevated TNF observation.…”

Effect of crystallinity and related surface properties on gene expression of primary fibroblasts

“…Under in vivo , more intensive synthesis of collagen was observed on low molecular chitosan than on high molecular weight chitosan what was associated with a prior reduction of the inflammatory response and improved wound healing. 56 TIMP-1 as a collagen degradation blocking factor was the most active after 1 day on samples with lower molecular weight (PCL45). An additional activity increase was observed on samples with higher crystallinity and lower wettability (PCL45w, PCL80w).…”