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

Chen, Guanyu, Svirskis, Darren, Lu, Weiyue, Ying, Man, Li, Hongyu, Liu, Min, Wen, Jingyuan·2021·Carbohydrate Polymers
DOI 10.1016/j.carbpol.2021.118592
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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.

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Metadata

Authors
Chen, G., Svirskis, D., Lu, W., Ying, M., Li, H., Liu, M., & Wen, J.
Venue
Carbohydrate Polymers
Publisher
Elsevier BV
Published
2021-12
Volume
273
Pages
118592
ISSN
0144-8617
DOI
10.1016/j.carbpol.2021.118592
Cited by
36
References
1
Language
en
Licence
Funders
  • University of Auckland
  • Fudan University

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