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Sustained release of PTX-incorporated nanoparticles synergized by burst release of DOX⋅HCl from thermosensitive modified PEG/PCL hydrogel to improve anti-tumor efficiency.

Abstract
As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX⋅HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX⋅HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX⋅HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX⋅HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX⋅HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX⋅HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX⋅HCl was observed to have a sustained releasing pattern in vitro and in vivo.
AuthorsShuxin Xu, Weiwei Wang, Xijing Li, Jianping Liu, Anjie Dong, Liandong Deng
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 62 Pg. 267-73 (Oct 01 2014) ISSN: 1879-0720 [Electronic] Netherlands
PMID24931190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Polyesters
  • polycaprolactone
  • Polyethylene Glycols
  • Doxorubicin
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, chemistry)
  • Carcinoma, Ehrlich Tumor (drug therapy, pathology)
  • Cell Line, Tumor
  • Delayed-Action Preparations (administration & dosage, chemistry)
  • Doxorubicin (administration & dosage, chemistry)
  • Drug Carriers (administration & dosage, chemistry)
  • Drug Liberation
  • Hydrogels (chemistry)
  • Mice, Inbred BALB C
  • Nanoparticles (administration & dosage, chemistry)
  • Paclitaxel (administration & dosage, chemistry)
  • Polyesters (chemistry)
  • Polyethylene Glycols (chemistry)
  • Temperature
  • Tumor Burden (drug effects)

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