Development of mutlifunctional nanoparticles self-assembled from trimethyl chitosan and fucoidan for enhanced oral delivery of insulin

Li Chu Tsai, Chien Ho Chen, Cheng Wei Lin, Yi Cheng Ho, Fwu Long Mi

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)141-150
頁數10
期刊International Journal of Biological Macromolecules
126
DOIs
出版狀態已發佈 - 四月 1 2019

指紋

Chitosan
Nanoparticles
Insulin
Medical problems
Glucosidases
Diabetes Complications
Epithelial Cells
Proteins
fucoidan
Encapsulation
Hypoglycemic Agents
Permeation
Biological Availability
Oral Administration
Gastrointestinal Tract
Monolayers
Permeability
Degradation
Fluids
Therapeutics

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

引用此文

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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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AU - Chen, Chien Ho

AU - Lin, Cheng Wei

AU - Ho, Yi Cheng

AU - Mi, Fwu Long

PY - 2019/4/1

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AB - 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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