Magnetic resonance activatable thermosensitive liposomes for controlled doxorubicin delivery

被引:19
|
作者
Alawak, Mohamad [1 ]
Mahmoud, Gihan [1 ,2 ]
Abu Dayyih, Alice [1 ]
Duse, Lili [1 ]
Pinnapireddy, Shashank Reddy [1 ]
Engelhardt, Konrad [1 ]
Awak, Ibrahim [3 ]
Woelk, Christian [4 ]
Koenig, Alexander M. [5 ]
Bruessler, Jana [1 ]
Bakowsky, Udo [1 ]
机构
[1] Univ Marburg, Dept Pharmaceut & Biopharmaceut, Robert Koch Str 4, D-35037 Marburg, Germany
[2] Helwan Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Cairo 11795, Egypt
[3] Hirsch Pharm, D-38126 Braunschweig, Germany
[4] Martin Luther Univ Halle Wittenberg, Inst Pharm, D-06120 Halle, Germany
[5] Univ Marburg, Dept Diagnost & Intervent Radiol, D-35032 Marburg, Germany
关键词
Drug delivery; Thermosensitive liposomes; Doxorubicin; Triggered release; Ultra high field magnetic resonance imaging; DRUG-DELIVERY; SENSITIVE LIPOSOMES; FOCUSED ULTRASOUND; MILD HYPERTHERMIA; RELEASE; MRI; THERAPY; EXTRAVASATION; FORMULATION; EFFICIENCY;
D O I
10.1016/j.msec.2020.111116
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
To limit the massive cytotoxicity of chemotherapeutic agents, it is desirable to establish an appropriate subtle blend of formulation design based on a dual-responsive strategy. In this study, a combined therapeutic platform based on magnetic thermosensitive liposomes (Lip(TS-GD)) was developed. The incorporation of chelated-gadolinium imparted magnetic properties to thermosensitive liposomes (Lip(TS)). The application of an ultra high field magnetic resonance imaging (UHF-MRI) induced hyperthermia, thus provided an improved chemotherapeutic effect of Doxorubicin (DOX). The paramagnetic platform demonstrated thermal sensitivity over a narrow temperature range starting at 37.8 degrees C, hence the release of DOX from Lip(TS-GD) can be well triggered by inducing hyperthermia using UHF-MRI application. The prepared Lip(TS-GD) were below 200 nm in diameter and an adequate release of DOX reaching 68% was obtained after 1 h UHF-MRI exposure. Profoundly, triple-negative breast cancer (TNBC) cells that were treated with Lip(TS-GD) and subjected thereafter to UHF-MRI exposure for 60 min showed 36% viability. Hemocompatibility studies of Lip(TS-GD) showed a physiological coagulation time and minimal hemolytic potential. Conclusively, Lip(TS-GD) guided local delivery of DOX to solid tumors will potentially raise the therapeutic index, thus reducing the required dose and frequency of DOX administered systemically without influencing the adjacent tissues.
引用
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页数:10
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