PLoS ONE (Jan 2012)

Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts.

  • Jing Li,
  • Changyang Gong,
  • Xiaodong Feng,
  • Xikun Zhou,
  • Xiaoping Xu,
  • Liang Xie,
  • Ruinan Wang,
  • Dunfang Zhang,
  • Hui Wang,
  • Peng Deng,
  • Min Zhou,
  • Ning Ji,
  • Yu Zhou,
  • Yun Wang,
  • Zhiyong Wang,
  • Ga Liao,
  • Ning Geng,
  • Liangyin Chu,
  • Zhiyong Qian,
  • Zhi Wang,
  • Qianming Chen

DOI
https://doi.org/10.1371/journal.pone.0033860
Journal volume & issue
Vol. 7, no. 4
p. e33860

Abstract

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BackgroundOSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts.Objective/purposeThe objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.MethodsA biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.ResultsThe hydrogel system was a free-flowing sol at 10 °C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.ConclusionsOur research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC.