N-trimethyl chitosan coated nano-complexes enhance the oral bioavailability and chemotherapeutic effects of gemcitabine

Guanyu Chen, Darren Svirskis, Weiyue Lu, Man Ying, Hongyu Li, Min Liu, Jingyuan Wen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

N-trimethyl chitosan (TMC) is a multifunctional polymer that can be used in various nanoparticle forms in the pharmaceutical, nutraceutical and biomedical fields. In this study, TMC was used as a mucoadhesive adjuvant to enhance the oral bioavailability and hence antitumour effects of gemcitabine formulated into nanocomplexes composed of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) conjugated with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). A central composite design was applied to achieve the optimal formulation. Cellular uptake and drug transportation studies revealed the nanocomplexes permeate over the intestinal cells via adsorptive-mediated and caveolae-mediated endocytosis. Pharmacokinetic studies demonstrated the oral drug bioavailability of the nanocomplexes was increased 5.1-fold compared with drug solution. In pharmacodynamic studies, the formulation reduced tumour size 3.1-fold compared with the drug solution. The data demonstrates that TMC modified nanocomplexes can enhance gemcitabine oral bioavailability and promote the anticancer efficacy.

Original languageEnglish (US)
Article number118592
JournalCarbohydrate Polymers
Volume273
DOIs
StatePublished - Dec 1 2021
Externally publishedYes

Keywords

  • Anticancer
  • Gemcitabine
  • N-trimethyl chitosan
  • Nanoparticle
  • Oral bioavailability
  • PLGA-TPGS

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Materials Chemistry

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