Back to Search
Start Over
N-trimethyl chitosan coated nano-complexes enhance the oral bioavailability and chemotherapeutic effects of gemcitabine.
- Source :
-
Carbohydrate polymers [Carbohydr Polym] 2021 Dec 01; Vol. 273, pp. 118592. Date of Electronic Publication: 2021 Aug 21. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Cell Line, Tumor
Chitosan chemical synthesis
Chitosan chemistry
Chitosan metabolism
Deoxycytidine chemistry
Deoxycytidine pharmacokinetics
Deoxycytidine therapeutic use
Drug Carriers chemical synthesis
Drug Carriers metabolism
Drug Liberation
Male
Mice, Inbred BALB C
Mice, Nude
Nanoparticles metabolism
Polylactic Acid-Polyglycolic Acid Copolymer chemical synthesis
Polylactic Acid-Polyglycolic Acid Copolymer chemistry
Polylactic Acid-Polyglycolic Acid Copolymer metabolism
Rats, Sprague-Dawley
Vitamin E chemical synthesis
Vitamin E chemistry
Vitamin E metabolism
Gemcitabine
Mice
Rats
Antineoplastic Agents therapeutic use
Deoxycytidine analogs & derivatives
Drug Carriers chemistry
Nanoparticles chemistry
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1344
- Volume :
- 273
- Database :
- MEDLINE
- Journal :
- Carbohydrate polymers
- Publication Type :
- Academic Journal
- Accession number :
- 34560993
- Full Text :
- https://doi.org/10.1016/j.carbpol.2021.118592