Comprehensive investigations of fibroin and poly(ethylenimine) functionalized fibroin nanoparticles for ulcerative colitis treatment

Abstract Ulcerative colitis causes a big burden to patients due to its complicated treatment and related side effects. Hence, alternative oral dosages are becoming increasingly important for targeted drug delivery, protection from enzymatic conditions and dose reduction to avoid unwanted effects. For this, two different nanoparticle formulations were produced, i.e., non-functionalized negatively charged and poly(ethylenimine) functionalized positively charged fibroin particles. Identified formulations were loaded with rhodamine B and the anti-inflammatory drug α-mangostin. Interactions with the biological barrier and the release behavior were determined. To this end, an in-vitro co-culture model consisting of epithelial (Caco-2) and mucus secreting goblet (HT29-MTX) cells was developed taking into account the mucus layer thickness in the state of ulcerative colitis. Both investigated nanoparticles were non-toxic, colloidal stable for at least 6 months, and showed average particle sizes of approx. 300 nm. Using Caco-2 and HT29-MTX cell ratios of 5:5 and 4:6 resulted in a mucus layer thickness of approx. 15 μm, representing diseased conditions. The negatively charged particles permeated the mucus layers and were internalized by the cells, while their positively charged counterparts were mucoadhesive. The provided data suggest that both nanoparticles represent promising candidates to deliver active drug candidates to the colon at diseased stage.