title: Biodegradable thermosensitive hydrogel for SAHA and DDP delivery: therapeutic effects on oral squamous cell carcinoma xenografts.
abstract: BACKGROUND
  OSCC 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
  The 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Feng
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Ruinan
authors.initials: R
authors.lastname: Wang
authors.forename: Dunfang
authors.initials: D
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Deng
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Ning
authors.initials: N
authors.lastname: Ji
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Ga
authors.initials: G
authors.lastname: Liao
authors.forename: Ning
authors.initials: N
authors.lastname: Geng
authors.forename: Liangyin
authors.initials: L
authors.lastname: Chu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006877:Hydroxamic Acids / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011108:Polymers / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D003692:Delayed-Action Preparations; D056572:Histone Deacetylase Inhibitors; D020100:Hydrogels; D006877:Hydroxamic Acids; D011108:Polymers; D000077337:Vorinostat