← Back to Search
The Mechanism Of Enhancement On Oral Absorption Of Paclitaxel By N-octyl-O-sulfate Chitosan Micelles.
Ran Mo, X. Jin, N. Li, Caoyun Ju, Minjie Sun, C. Zhang, Q. Ping
Published 2011 · Materials Science, Medicine
Download PDFAnalyze on Scholarcy
The overall objective of the present investigation was to demonstrate the effect of N-octyl-O-sulfate chitosan (NOSC) micelles on enhancing the oral absorption of paclitaxel (PTX) in vivo and in vitro, and identify the mechanism of this action of NOSC. In vivo, the oral bioavailability of PTX loaded in NOSC micelles (PTX-M) was 6-fold improved in comparison with that of an orally dosed Taxol(®). In the Caco-2 uptake studies, NOSC micelles brought about a significantly higher amount of PTX accumulated in Caco-2 cells via both clathrin- and caveolae-mediated endocytosis, and NOSC had the effect on inhibiting PTX secreted by P-glycoprotein (P-gp), which was also proved by the studies on rhodamine 123 incorporated in NOSC micelles, fluorescence labeled micelles. The mechanism of NOSC on P-gp inhibition was demonstrated in connection with interfering the P-gp ATPase by NOSC rather than reducing the P-gp expression. Moreover, NOSC with the concentration approaching the critical micellar concentration (CMC) had the strongest effect on P-gp inhibition. In the Caco-2 transport studies, the presence of verapamil and NOSC both improved the transport of Taxol(®), which further certified the effect of NOSC on P-gp inhibition, and PTX-M enhanced the permeability of PTX compared with Taxol(®). The apparent permeability coefficient (Papp) of PTX-M decreased significantly at 4 °C in comparison with at 37 °C, which indicated a predominant active endocytic mechanism for the transport of PTX-M, a P-gp-independent way. Furthermore, the transcytosis of PTX-M was via clathrin-mediated rather than caveolae-mediated. In addition, the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers had no significant change during the transport study, which pointed out that NOSC had no effect on opening the intercellular tight junctions. Based on the obtained results, it is suggested that NOSC micelles might be a potentially applicable tool for enhancing the oral absorption of P-gp substrates.
This paper references
Oral Delivery of Taxanes
M. Malingré (2004)
Self-assembly and characterization of paclitaxel-loaded N-octyl-O-sulfate chitosan micellar system.
C. Zhang (2004)
Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study.
J. Szebeni (1998)
Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody.
E. B. Mechetner (1992)
Endocytosis of Murine Norovirus 1 into Murine Macrophages Is Dependent on Dynamin II and Cholesterol
J. W. Perry (2010)
Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine.
A. Sparreboom (1997)
Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed micelles: some properties, loading with paclitaxel, and modulation of P-glycoprotein-mediated efflux.
Rupa D. Dabholkar (2006)
Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate chitosan micelles loaded with paclitaxel.
C. Zhang (2008)
Exploiting the vitamin B12 pathway to enhance oral drug delivery via polymeric micelles.
M. Francis (2005)
Oral microemulsions of paclitaxel: in situ and pharmacokinetic studies.
Adwoa O. Nornoo (2009)
Transmucosal macromolecular drug delivery.
C. Prego (2005)
Enhanced oral absorption and decreased elimination of paclitaxel in mice cotreated with cyclosporin A.
J. van Asperen (1998)
Absorption of poorly water soluble drugs subject to apical efflux using phospholipids as solubilizers in the Caco-2 cell model.
Susanne B. Kapitza (2007)
Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles.
Y. Hu (2007)
Efficacy of novel P-glycoprotein inhibitors to increase the oral uptake of paclitaxel in mice
H. A. Bardelmeijer (2004)
Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signaling
M. Koivusalo (2010)
Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes [see comments]
P. M. Chaudhary (1992)
Polymeric micelles in oral chemotherapy.
L. Bromberg (2008)
Cyclosporin A-loaded poly(ethylene glycol)-b-poly(d,l-lactic acid) micelles: preparation, in vitro and in vivo characterization and transport mechanism across the intestinal barrier.
Y. Zhang (2010)
Endocytosis inhibitors prevent poly(amidoamine) dendrimer internalization and permeability across Caco-2 cells.
Kelly M. Kitchens (2008)
Quantum dots for tracking cellular transport of lectin-functionalized nanoparticles.
X. Gao (2008)
Paclitaxel and its formulations.
A. K. Singla (2002)
A. Kay (1991)
Different internalization pathways of polymeric micelles and unimers and their effects on vesicular transport.
G. Sahay (2008)
Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery.
Yu-Hsin Lin (2007)
Enhanced oral absorption of paclitaxel in N-deoxycholic acid-N, O-hydroxyethyl chitosan micellar system.
H. Li (2010)
Regulated portals of entry into the cell
S. Conner (2003)
Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles.
M. Agüeros (2010)
Molecular properties of WHO essential drugs and provisional biopharmaceutical classification.
N. A. Kasim (2004)
Methoxypolyethylene glycol-block-polycaprolactone diblock copolymers reduce P-glycoprotein efflux in the absence of a membrane fluidization effect while stimulating P-glycoprotein ATPase activity.
J. Zastre (2007)
Expression and activity of the multidrug resistance P - glycoprotein in human peripheral
Lipid nanocarriers improve paclitaxel transport throughout human intestinal epithelial cells by using vesicle-mediated transcytosis.
E. Roger (2009)
Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs.
K. Y. Win (2005)
Syl611, a novel semisynthetic taxane derivative, reverses multidrug resistance by p-glycoprotein inhibition and facilitating inward transmembrane action
Yi Zhang (2009)
A novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery.
Y. Xu (2010)
Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of intravenous drugs.
C. Zhang (2008)
Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: in vitro/in vivo case studies.
P. Constantinides (2007)
PLGA Nanoparticles Stabilized with Cationic Surfactant: Safety Studies and Application in Oral Delivery of Paclitaxel to Treat Chemical-Induced Breast Cancer in Rat
V. Bhardwaj (2009)
Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes.
P. M. Chaudhary (1992)
Enhanced Oral Bioavailability of Paclitaxel by Coadministration of the P-Glycoprotein Inhibitor KR30031
J. Woo (2004)
Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2).
A. Kotzé (1998)
Efavirenz-loaded polymeric micelles for pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailability [corrected].
D. Chiappetta (2010)
Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity.
E. Collnot (2007)
Taxol: the first of the taxanes, an important new class of antitumor agents.
E. Rowinsky (1992)
Oral delivery of peptide drugs using nanoparticles self-assembled by poly(gamma-glutamic acid) and a chitosan derivative functionalized by trimethylation.
F. Mi (2008)
Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier.
Frédéric Mathot (2007)
Development and in vivo evaluation of an oral drug delivery system for paclitaxel.
J. Iqbal (2011)
loride inhibits macropinocytosis by lowering submembranous pH and preventing Rac 1 and Cdc 42 signaling
M Koivusalo (2010)
This paper is referenced by
The construction and characterization of hybrid paclitaxel-in-micelle-in-liposome systems for enhanced oral drug delivery.
Yimu Li (2017)
Synergistically Improved Anti-tumor Efficacy by Co-delivery Doxorubicin and Curcumin Polymeric Micelles.
J. Wang (2015)
Applications of chitosan nanoparticles to enhance absorption and bioavailability of tea polyphenols: A review
J. Liang (2017)
Chitosan and its derivatives-based nano-formulations in drug delivery
Y. Tian (2016)
Is nanotechnology a boon for oral drug delivery?
Udita Agrawal (2014)
Nanocomposite hydrogel incorporating gold nanorods and paclitaxel-loaded chitosan micelles for combination photothermal-chemotherapy.
N. Zhang (2016)
Sulfonated and sulfated chitosan derivatives for biomedical applications: A review.
S. Dimassi (2018)
Shedding light on interaction of so called inactive ingredients (excipients) with permeability-glycoprotein
Kiran Katrajkar (2019)
Improving celecoxib bioavailability with β-casein nanocarriers
Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes
Xiaoyou Qu (2018)
Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics
J. Lee (2019)
Mitoxantrone-loaded chitosan/hyaluronate polyelectrolyte nanoparticles decorated with amphiphilic PEG derivates for long-circulating effect.
J. Wang (2018)
Nanostructured lipid carriers as oral delivery systems for improving oral bioavailability of Nintedanib by promoting intestinal absorption.
Y. Zhu (2020)
Stepwise orthogonal click chemistry toward fabrication of paclitaxel/galactose functionalized fluorescent nanoparticles for HepG2 cell targeting and delivery.
Chian-Hui Lai (2013)
Acid/redox dual-activated liposomes for tumor-targeted drug delivery and enhanced therapeutic efficacy
Xuefan Xu (2015)
Synergistic effects of A-B-C-type amphiphilic copolymer on reversal of drug resistance in MCF-7/ADR breast carcinoma
L. Zhang (2016)
Solubility and bioavailability enhancement study of lopinavir solid dispersion matrixed with a polymeric surfactant - Soluplus.
P. Zi (2019)
Nanocarrier possibilities for functional targeting of bioactive peptides and proteins: state-of-the-art
C. Moutinho (2012)
Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment.
Assogba G Assanhou (2015)
Multilayer micro-dispersing system as oral carriers for co-delivery of doxorubicin hydrochloride and P-gp inhibitor.
C. Feng (2017)
A novel ligand conjugated nanoparticles for oral insulin delivery
C. Liu (2016)
Advances and applications of chitosan-based nanomaterials as oral delivery carriers: A review.
Xuqian Lang (2020)
Search for a 5-CT alternative. In vitro and in vivo evaluation of novel pharmacological tools: 3-(1-alkyl-1H-imidazol-5-yl)-1H-indole-5-carboxamides, low-basicity 5-HT7 receptor agonists.
G. Latacz (2018)
Nanoparticles based on chitosan hydrochloride/hyaluronic acid/PEG containing curcumin: In vitro evaluation and pharmacokinetics in rats.
Yurui Xu (2017)
REVIEW Polymeric micelles: authoritative aspects for drug delivery
Sushant S. Kulthe (2012)
The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo.
J. Wang (2015)
n vitro evaluation on novel modified chitosan for targeted antitumor drug elivery
ing Qu (2012)
Enhancement on oral absorption of paclitaxel by multifunctional pluronic micelles
Yimu Li (2013)
Trimethyl chitosan based conjugates for oral and intravenous delivery of paclitaxel.
Rui He (2017)
A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.
Z. Zhang (2013)
Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer.
Feiyang Deng (2017)
Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation
Ding Qu (2014)See more