An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and synthesized for oral delivery of paclitaxel (PTX) to improve its oral bioavailability by increasing its water solubility and bypassing the P-gp drug efflux pumps. CQ conjugate had low critical micelle concentration (55.14 μg/mL), and could self assemble in aqueous condition to form polymeric micelles (PMs). PTX-loaded CQ PMs displayed a particle size of 185.8 ± 4.6 nm and polydispersity index (PDI) of 0.134 ± 0.056. The drug-loading content (DL) and entrapment efficiency (EE) were 33.62 ± 1.34% and 85.63 ± 1.26%, respectively. Moreover, PTX-loaded CQ PMs displayed similar sustained-release profile in simulated gastrointestinal fluids (pH 1.2/pH 6.8) and PBS (pH 7.4). In situ intestinal absorption experiment showed that PTX-loaded CQ PMs significantly improved the effective permeability of PTX as compared to verapamil (P < 0.01). Likewise, PTX-loaded CQ PMs significantly enhanced the oral bioavailability of PTX, resulting in strong antitumor efficacy against tumor xenograft models with better safety profile as compared to Taxol(®) and Taxol(®) with verapamil. Overall, the results implicate that CQ PMs are promising vehicles for the oral delivery of water-insoluble anticancer drugs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biomaterials.2014.05.053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Procedurally Targeted Delivery of Antitumor Drugs Using FAPα-Responsive TPGS Dimer-Based Flower-like Polymeric Micelles.
ACS Appl Bio Mater
October 2023
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
To overcome the intestinal epithelium barrier and achieve a better antitumor effect, the procedurally targeting flower-like nanomicelles for oral delivery of antitumor drugs were designed based on FAPα-responsive TPGS1000 dimer (TPGS-Gly-Pro-TPGS) and L-carnitine linked poly(2-ethyl-2-oxazoline)--poly(D, l-lactide) (Car-PEOz--PLA). As expected, compared with unmodified polymeric micelles (TT-PMs) composed of TPGS-Gly-Pro-TPGS, L-carnitine conjugated polymeric micelles (CTT-PMs) formed from both TPGS-Gly-Pro-TPGS and Car-PEOz--PLA with favorable stability in simulated gastrointestinal fluid and FAPα-dependent release capability exhibited remarkably enhanced cellular uptake and transmembrane transport through OCTN2 mediation confirmed by fluorescence immunoassay, which was intuitively evidenced by stronger fluorescence within epithelial cells, and the basal side of small intestinal epithelium of mice being given intragastric administration of DiI-labeled micelles. The transport of CTT-PMs across the intestinal epithelium in an intact form was mediated by clathrin along the intracellular transport pathway of endosome-lysosome-ER-Golgi apparatus.
View Article and Find Full Text PDFEvaluation and antitumor mechanism of functionalized chitosan-based polymeric micelles for oral delivery of paclitaxel.
Int J Pharm
September 2022
Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address:
D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-modified carboxymethyl chitosan-rhein (TCR) polymeric micelles (PMs) self-assembled by TCR conjugate were constructed for oral delivery of paclitaxel (PTX). PTX-loaded TCR PMs with a drug loading capacity of 47.52 ± 1.
View Article and Find Full Text PDFEvaluation of intestinal permeation enhancement with carboxymethyl chitosan-rhein polymeric micelles for oral delivery of paclitaxel.
Int J Pharm
January 2020
Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address:
Polymeric micelles (PMs) are currently under investigation as potential nanocarriers for oral administration of paclitaxel (PTX). Previously, we developed amphiphilic carboxymethyl chitosan-rhein (CR) conjugate for oral delivery of PTX. PTX-loaded CR PMs exhibited a homogeneous and small size (<200 nm) with a drug loading capacity (DL) of 35.
View Article and Find Full Text PDFPreparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel.
Carbohydr Polym
February 2019
Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address:
An amphiphilic carboxymethyl chitosan-rhein (CR) conjugate was prepared, characterized, and evaluated as a potential carrier material for oral delivery of paclitaxel (PTX). CR conjugate self-assembled in aqueous environment into CR polymeric micelles (CR PMs). The drug loading capacity and entrapment efficiency of PTX-loaded CR PMs were 35.
View Article and Find Full Text PDFAmphiphilic carboxymethyl chitosan-quercetin conjugate with P-gp inhibitory properties for oral delivery of paclitaxel.
Biomaterials
August 2014
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address:
An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and synthesized for oral delivery of paclitaxel (PTX) to improve its oral bioavailability by increasing its water solubility and bypassing the P-gp drug efflux pumps. CQ conjugate had low critical micelle concentration (55.14 μg/mL), and could self assemble in aqueous condition to form polymeric micelles (PMs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!