Injectable and Biodegradable Poly(Organophosphazene) Gel Containing Silibinin: Its Physicochemical Properties and Anticancer Activity

• Published in: Journal of pharmaceutical sciences 2012-07, Vol.101 (7), p.2382-2391
• Main Authors: Cho, Jung-Kyo, Park, Jung Won, Song, Soo-Chang
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Antioxidants - administration & dosage; Antioxidants - chemistry; Antioxidants - therapeutic use; biodegradable polymers; Biological and medical sciences; Cell Line, Tumor; colon cancer; Colonic Neoplasms - drug therapy; controlled release/delivery; Drug Carriers - chemistry; General pharmacology; Humans; hydrogels; Hydrogels - chemistry; injectables; Injections; Medical sciences; Mice; Organophosphorus Compounds - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; poly(organophosphazene); polymeric drug delivery systems; Polymers - chemistry; silibinin; Silybin; Silybum marianum - chemistry; Silymarin - administration & dosage; Silymarin - chemistry; Silymarin - therapeutic use; thermosensitive
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23137

The biodegradable poly(organophosphazene) hydrogels were developed as a locally injectable drug carrier for a hydrophobic silibinin to overcome its limited bioavailability. The aqueous solution of poly(organophosphazene) enhanced the solubility of silibinin up to 2000 times compared with that of phosphate buffered saline (0.0415 vs. 84.55mg/mL). Both aqueous polymer solutions with and without silibinin showed a sol–gel transition as a function of temperature. A faster in vitro degradation rate of the gel and drug release rate from the gel at pH 6.8 than those at pH 7.4 were observed when the degradation and release study on hydrogels were conducted at 37°C. Silibinin was sustainedly released from the hydrogel mainly by a diffusion-controlled mechanism. The silibinin released from the hydrogel was shown to be effective considering the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In the HT-29 xenografted mice model, the intratumorally injected hydrogel containing silibinin exhibited a good antitumor effect in comparison with the control groups. The Western blotting indicated that one of the reasons for the enhanced antitumor effect of the hydrogel system was the sustained antiangiogenic effect of silibinin. The poly(organophosphazene) gels are expected to be an effective candidate of the locally injectable drug carrier for silibinin.