Sodium dodecyl sulfate-modified doxorubicin-loaded chitosan-lipid nanocarrier with multi polysaccharide-lecithin nanoarchitecture for augmented bioavailability and stability of oral administration in vitro and in vivo

Chia Wei Su, Min Yu Chiang, Yu Ling Lin, Nu Man Tsai, Yen Po Chen, Wei Ming Li, Chin Hao Hsu, San-Yuan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core-shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer's patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.

Original languageEnglish
Pages (from-to)962-972
Number of pages11
JournalJournal of Biomedical Nanotechnology
Volume12
Issue number5
DOIs
StatePublished - 1 May 2016

Keywords

  • Bioavailability
  • Caco-2 Cell Monolayers
  • Intestinal Absorption
  • Oral Delivery
  • Triglyceride

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