Thermogelling emulsions for vascular embolization and sustained release of drugs.
Thermogelling emulsion system was developed to function as an embolic agent and sustained release system. PEG-PLGA-PEG triblock copolymer was synthesized, and blended with oily phase (Lipiodol(R)) to constitute the thermogelling emulsions. Because the polymer-rich aqueous phase dramatically increases viscosity in response to temperature change, especially within the range between 20 and 30 degrees C, the emulsions produce a stop-flowing gel with oil droplets entrapped. Thereafter, paclitaxels were released from the oily reservoir of gelled emulsions in a controlled manner. Reduced burst effect and steady drug release with near zero-order release kinetics were observed. Human umbilical vein endothelial cells (HUVEC) were collected from fresh umbilical cords for in vitro antiangiogenesis test. It demonstrated that the sustained release of paclitaxel from emulsions inhibited growth of HUVEC and that the IC(50), calculated according to release rate, was consistent with that obtained from free drug study. In addition, the emulsions forming a depot in situ inside the injection site of the blood vessel in rabbit ear obstructed the blood flow, and being monitored under X-ray angiography. Taken together, this study proved the feasibility of the thermogelling emulsions for vascular embolization and sustained drug release. The results presented a potential system for arterial transcatheter embolization on hepatocellular carcinoma combined with anti-angiogeneic treatment.
Kan
Pei
P
Biomedical Engineering Center, Industrial Technology Research Institute, HsinChu 300, Taiwan, Republic of China. PeiKan@itri.org.tw
Lin
Xi-Zhang
XZ
Hsieh
Ming-Fa
MF
Chang
Ken-Yuen
KY
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D004621:Embolization, Therapeutic / Q000295:instrumentation* / Q000379:methods*; D004655:Emulsions / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D013696:Temperature; D014783:Viscosity
D004655:Emulsions; D020100:Hydrogels; D011108:Polymers; D017239:Paclitaxel