Mucoadhesive particles with enhancing intestinal absorption capacity as drug delivery platform for vitamin E

INTRODUCTION M-cells are the specialised antigen sampling sites of the intestinal immune system and represent a potential portal for mucosal drug and vaccine delivery since they possess a high transcytotic capacity and are able to transport a broad range of materials including particulates. To increase bioadhesion to enterocytes in the gastrointestinal tract, targeting ligands (such as lectins) are of special interest, as they mediate highly specific binding to epithelial cell subpopulations, effected by interaction of carbohydrate-binding sites of lectin with sugar residues in the glycocalyx of epithelial cells. Exploiting lectins for bioadhesive drug delivery purposes, this cell-specific interaction can result in active receptor-mediated endocytosis and/or transcytosis of the drug delivery system. Vitamin E is a class of lipid-soluble antioxidant molecules widely used in food, cosmetic and pharmaceutical fields. Unfortunately due to its high sensitivity to external stimuli such as light, heat and oxygen, it rapidly degrades and this limits its applications. The aim of this work is to formulate mucoadhesive and biodegradable polymeric particles intended for oral use to enhance the intestinal absorption of γ-tocopherol. Poly(lactic-co-glycolic acid) (PLGA) based carriers have been produced with the classic nanoprecipitation method, which is an easy, reproducible and scale up method. The biocompatible polysaccharide chitosan have been added to the formulation to increase the mucoadhesion of the particles, which is exert due to its polycation nature and ability to interact with mucus producing surfaces. Moreover the particles surface has been covalently modified with lectins obtained from Sambucus ebulus L., to further increase mucoadhesiveness and cell interactions. RESULTS AND DISCUSSION Different formulations have been performed to select the optimal conditions and components percentages to be used in the carrier system, particularly regarding the kind of surfactants/stabilizers (poly(vinyl alcohol) (PVA), Poloxamer 407, Tween 80 or PEGylated poly(lactic acid) (mPEG-PLA)). The γ-tocopherol delivery system has been optimized regarding the encapsulation efficacy, the particles morphology and the cell penetration ability. Spherical particles have been produced and characterize with dynamic light scattering (< 1 μm) and microscopy techniques.