Enhanced paracellular and transcellular paclitaxel permeation by chitosan–vitamin E succinate–N-acetyl-l-cysteine copolymer on Caco-2 cell monolayer

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 16; no. 4; pp. 1 - 16
• Main Authors: Lian, He, Zhang, Tianhong, Sun, Jin, Pu, Xiaohui, Tang, Yilin, Zhang, Youxi, He, Zhonggui
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2014; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Biotechnology; Cellular; Characterization and Evaluation of Materials; Chemistry and Materials Science; Copolymers; Cross-disciplinary physics: materials science; rheology; Drugs; Efflux; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Inorganic Chemistry; Lasers; Materials Science; Methods of nanofabrication; Methods. Procedures. Technologies; Nanoparticles; Nanostructure; Nanotechnology; Optical Devices; Optics; Others; Penetration; Permeation; Photonics; Physical Chemistry; Physics; Research Paper; Self-assembly; Toxicity; Various methods and equipments; Paracellular; Transcellular; Nanomedicine; CS–VES–NAC; Paclitaxel; Drugs; Cysteine; Toxicity; Cytotoxicity; Confocal microscopy; Drug carrier; CS-VES-NAC; Self-assembly; Copolymers; Endocytosis; Aqueous solutions; Monolayers; Chitosan; Medical application
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-014-2355-9

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.