Thermosensitive poly(organophosphazene)-paclitaxel conjugate gels for antitumor applications.
A poly(organophosphazene)-PTX conjugate was synthesized by a covalent ester linkage between PTX and carboxylic acid-terminated poly(organophosphazene), which can be readily modified by various hydrophobic, hydrophilic, and other functional substitutes. The physicochemical properties, hydrolytic degradation and PTX release behaviors of the polymer-PTX conjugate were characterized, in addition to the in vitro and in vivo antitumor activities. The aqueous solutions of these conjugates showed a sol-gel transition behavior that depended on temperature changes. The in vitro antitumor activity of the polymer-PTX conjugate was investigated by an MTT assay against human tumor cell lines. From the in vivo antitumor activity studies with tumor-induced (xenografted) nude mice, the polymer-paclitaxel conjugate hydrogels after local injection at the tumor site were shown to inhibit tumor growth more effectively and longer than paclitaxel and saline alone, indicating that the tumor-active paclitaxel from the polymer-PTX conjugate hydrogel is released slowly over a longer period of time and effectively accumulated locally in the tumor sites. These combined observations suggest that this poly(organophosphazene)-PTX conjugate holds promise for use in clinical studies as single and/or combination therapies.
Chun
Changju
C
Division of Life Science, Korea Institute of Science and Technology, Cheongryang, Seoul 136-791, Republic of Korea.
Lee
Sun Mi
SM
Kim
Sang Yoon
SY
Yang
Han Kwang
HK
Song
Soo-Chang
SC
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005782:Gels / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology*; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity; D013696:Temperature; D014867:Water / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005782:Gels; D009943:Organophosphorus Compounds; D011108:Polymers; C515246:poly(organophosphazene); D014867:Water; D017239:Paclitaxel