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 language | English (US) |
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Article number | 118592 |
Journal | Carbohydrate Polymers |
Volume | 273 |
DOIs | |
State | Published - Dec 1 2021 |
Externally published | Yes |
Keywords
- Anticancer
- Gemcitabine
- N-trimethyl chitosan
- Nanoparticle
- Oral bioavailability
- PLGA-TPGS
ASJC Scopus subject areas
- Organic Chemistry
- Polymers and Plastics
- Materials Chemistry