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.