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  • Title: Development of mutlifunctional nanoparticles self-assembled from trimethyl chitosan and fucoidan for enhanced oral delivery of insulin.
    Author: Tsai LC, Chen CH, Lin CW, Ho YC, Mi FL.
    Journal: Int J Biol Macromol; 2019 Apr 01; 126():141-150. PubMed ID: 30586591.
    Abstract:
    Oral administration is a highly attractive approach for the delivery of protein drugs. However, oral protein therapeutics typically exhibit extremely poor bioavailability due to the harsh gastrointestinal (GI) environments and low permeability of protein across the intestinal barrier. Trimethyl chitosan (TMC) shows excellent mucoadhesive and absorption-enhancing properties while fucoidan (FD) has hypoglycemic effects and can prevent diabetes-related complications. Here we report, for the first time, that TMC combined with FD can be developed to a mutlifunctional nanoplatform for enhancing the transepithelial permeation of insulin through the intestinal epithelial cell barrier and inhibiting the α-glucosidase activity. TMC and FD self-assembled into spherical nanoparticles (NPs) for insulin encapsulation. TMC/FD NPs protected insulin against degradation by releasing insulin in a pH-dependent manner in the gastrointestinal tract fluids. The NPs were able to modulate the barrier function of the Caco-2 intestinal epithelial cell monolayer, and enhance paracellular transport of insulin across the intestinal barrier. TMC/FD NPs also showed α-glucosidase inhibitory activity, with an inhibition ratio of 33.2% at 2 mg/mL. The superior transepithelial absorption enhancing property of the TMC/FD NPs is expected to combine in the future with the functions of fucoidan against diabetes-related complications for development of advanced mutlifunctional therapeutic platforms for diabetes.
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