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/PURPOSE:

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: 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
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e33860 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22529899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Delayed-Action Preparations
• Histone Deacetylase Inhibitors
• Hydrogels
• Hydroxamic Acids
• Polymers
• Vorinostat

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (blood supply, drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Delayed-Action Preparations
• Drug Delivery Systems
• Female
• Histone Deacetylase Inhibitors (administration & dosage)
• Hydrogels (chemical synthesis, chemistry, toxicity)
• Hydroxamic Acids (administration & dosage)
• Mice
• Mice, Nude
• Mouth Neoplasms (blood supply, drug therapy)
• Neovascularization, Pathologic (drug therapy)
• Polymers (chemical synthesis, therapeutic use, toxicity)
• Vorinostat
• Xenograft Model Antitumor Assays