하이푸를 이용한 항암제 함유 온도민감 리포좀의 표적 전달능 평가를 위한 MRI의 역할: 동물실험 연구
- 주저자 : Kim HR, Park SJ, Choi KS, You DG, Um W, Kim JH, Kim YS, Park JH - 영문 제목 : MRI monitoring of tumor-selective anticancer drug delivery with stable thermosensitive liposomes triggered by high-intensity focused ultrasound - 한글 제목 : 하이푸를 이용한 항암제 함유 온도민감 리포좀의 표적 전달능 평가를 위한 MRI의 역할: 동물실험 연구 - 저널 : Mol Pharmaceutics - 연도 : 2016 - 권 / 쪽 : 13 / 1528-1539 - 초록 : Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 °C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 °C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high-intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU.
KEYWORDS: MRI; drug release monitoring; elastin-like polypeptide; heat-triggered drug release; intratumoral accumulation; thermosensitive liposome