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.
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页数:10
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