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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
- Source :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 62
- Publication Year :
- 2014
-
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(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(e-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.
- Subjects :
- Drug
Paclitaxel
media_common.quotation_subject
Polyesters
Pharmaceutical Science
Nanoparticle
Antineoplastic Agents
macromolecular substances
Pharmacology
complex mixtures
Polyethylene Glycols
chemistry.chemical_compound
In vivo
Cell Line, Tumor
Animals
Carcinoma, Ehrlich Tumor
media_common
Antitumor activity
Drug Carriers
Mice, Inbred BALB C
Chemistry
technology, industry, and agriculture
Temperature
Hydrogels
In vitro
Tumor Burden
Drug Liberation
Doxorubicin
Delayed-Action Preparations
Biophysics
Doxorubicin Hydrochloride
Nanoparticles
Ethylene glycol
Subjects
Details
- ISSN :
- 18790720
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....e3fe28729a052e1b6716264a10f8d7c4