- 주저자 : Park SM, Kim YS, Kim HR, Choi KS, et al - 영문 제목 : Novel temperature triggered liposomes with high stability: formulation, in vitro evaluation, and in vivo study combined with high-intensity focused ultrasound - 한글 제목 : 새로운 고안정성의 온도민감형 리포좀:조성, 하이푸를 이용한 생체내외 연구 - 저널 : J Contol Release - 연도 : 2013 - 권 / 쪽 : 170 / 373-379 - 초록 : We developed a novel temperature-sensitive liposome, STL composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG-2000), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP). The STL had a unilamellar spherical shape with a mean diameter of 160 nm. Doxorubicin (DOX) was encapsulated by the STL using an ammonium sulfate gradient method with a lipid to drug ratio of 1:0.2 (w/w), resulting in 95% loading efficiency. The STL exhibited better stability than conventional low temperature sensitive liposome (LTSL-lysolipid-based temperature sensitive liposomes; DPPC:MSPC:DSPE-PEG-2000=90:10:4) at 37 °C in the presence of serum; there was rapid release of doxorubicin in the range of 39-42 °C (≥95% release at 42 °C within 10s). A confocal microscope revealed that DOX encapsulated in STL (STL-DOX) was taken up much better by cell nuclei at 42 °C than at 37 °C. The difference in cell viability between 37 and 42 °C was 63% relative to STL-DOX and 18% for LTSL-DOX. The pharmacokinetics (PK) and antitumor effect of STL-DOX combined with high-intensity focused ultrasound (HIFU) were studied, and compared with LTSL. An in vivo study demonstrated that STL-DOX is highly stable, with a long circulating property (half life=2.03±0.77 h) in HIFU-untreated mice, and resulted in significant tumor regression for 2 days after intravenous injection of STL-DOX at 5 mg DOX/kg in combination with HIFU. These results are better than conventional LTSL, for which the blood circulation time is short (0.92±0.17 h) and inhibition of tumor growth is weak. These results indicate that the properties of stability at 37 °C and burst release at 42 °C of STL-DOX act synergistically against tumors.
KEYWORDS: Drug delivery system; Elastin-like polypeptide; Heat-triggered drug release; Mild hyperthermia; Thermosensitive liposome"