4.5 Article

Thermosensitive Hydrogel System With Paclitaxel Liposomes Used in Localized Drug Delivery System for In Situ Treatment of Tumor: Better Antitumor Efficacy and Lower Toxicity

Journal

JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 105, Issue 1, Pages 194-204

Publisher

WILEY-BLACKWELL
DOI: 10.1002/jps.24693

Keywords

thermosensitive; paclitaxel liposome; intratumoral retention; pharmacodynamics; tissue distribution; biodegradable polymers; cancer chemotherapy; controlled release; injectables; lymphatic transport; thermal gels

Funding

  1. Pharmacy Laboratory Centre of Shenyang Pharmaceutical University
  2. Animal Centre of Shenyang Pharmaceutical University

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Intratumoral delivery of chemotherapeutic agents may provide drug localization within the tumor and divert the drug from nontarget organs to improve toxicity and increase efficacy. Thermosensitive injectable hydrogel system may be suitable for the treatment of pancreatic cancer. A study was carried out to examine the efficacy and toxicity of paclitaxel (PTX) liposome gel as a local chemotherapy system against pancreatic cancer in tumor-bearing mice model. The thermosensitive hydrogel we prepared had an appropriate sol-to-gel transition temperature and particle size and morphology study showed this new dosage form possessed physical stability of drug without precipitation and particle size growth of liposome. PTX-lip-gel release in vitro showed a much more slowly release than PTX-lip. The PTX-lip-gel system was proven to have a good retention inside of tumor tissue by intratumoral retention experiments. The in vivo trials showed a better balance between antitumor efficacy and systemic safety in PTX-lip-gel group than in other groups at the equal drug dose. In conclusion, the PTX-lip-gel we prepared in this study provided a high local PTX concentration, sustained and stable drug release, extend drug retention inside of tumor, and low toxicity to normal tissues. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

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