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The online version of this article (doi:10.1007/s11051-014-2355-9) contains supplementary material, which is available to authorized users.
The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate–N-acetyl-l-cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS–VES–NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS–VES–NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS–VES–NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS–VES–NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS–VES–NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS–VES–NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.
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Supplementary material 1 (DOC 234 kb)11051_2014_2355_MOESM1_ESM.doc
Dunnhaupt S, Barthelmes J, Rahmat D, Leithner K, Thurner CC, Friedl H, Bernkop-Schnurch A (2012) S-protected thiolated chitosan for oral delivery of hydrophilic macromolecules: evaluation of permeation enhancing and efflux pump inhibitory properties. Mol Pharm 9(5):1331–1341. doi: 10.1021/mp200598j
Gradauer K, Vonach C, Leitinger G, Kolb D, Frohlich E, Roblegg E, Bernkop-Schnurch A, Prassl R (2012) Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties. Int J Nanomedicine 7:2523–2534. doi: 10.2147/ijn.s29980
Lian H, Sun J, Yu YP, Liu YH, Cao W, Wang YJ, Sun YH, Wang SL, He ZG (2011) Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery. Int J Nanomedicine 6:3323–3334. doi: 10.2147/ijn.s26305
Lian H, Zhang TH, Sun J, Liu XH, Ren GL, Kou LF, Zhang YX, Han XP, Ding WY, Ai XY, Wu CN, Li L, Wang YJ, Sun YH, Wang SL, He ZG (2013a) Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan–vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism. Mol Pharm 10:3447–3458. doi: 10.1021/mp400282r CrossRef
Qiu L, Zheng C, Zhao Q (2012) Mechanisms of drug resistance reversal in Dox-resistant MCF-7 cells by pH-responsive amphiphilic polyphosphazene containing diisopropylamino side groups. Mol Pharm 9(5):1109–1117. doi: 10.1021/mp200356w
- Enhanced paracellular and transcellular paclitaxel permeation by chitosan–vitamin E succinate–N-acetyl-l-cysteine copolymer on Caco-2 cell monolayer
- Publication date
- Springer Netherlands
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