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Short Drug–Light Intervals Improve Liposomal Chemophototherapy in Mice Bearing MIA PaCa-2 Xenografts
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-04-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00052 Dandan Luo 1 , Kevin A. Carter 1 , Jumin Geng 1 , Xuedan He 1 , Jonathan F. Lovell 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-04-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00052 Dandan Luo 1 , Kevin A. Carter 1 , Jumin Geng 1 , Xuedan He 1 , Jonathan F. Lovell 1
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Chemophototherapy (CPT) is an emerging tumor treatment that combines phototherapy and chemotherapy. Long-circulating (LC) liposomes can stably incorporate 2 mol % porphyrin-phospholipid (PoP) in the bilayer and load doxorubicin (Dox) to generate LC-Dox-PoP liposomes, for single-agent CPT. Following intravenous administration to mice, LC-Dox-PoP liposomes (2 mg/kg Dox) circulated with similar blood concentration ranges produced by a typical human clinical dose of DOXIL (50 mg/m2 Dox). This dosing approach aims to achieve physiologically relevant Dox and PoP concentrations as well as CPT vascular responses in mice bearing subcutaneous human pancreatic MIA PaCa-2 xenografts. Phototreatment with 2 mg/kg LC-Dox-PoP induced vascular permeabilization, leading to a 12.5-fold increase in Dox tumor influx estimated by a pharmacokinetic model, based on experimental data. Shorter drug–light intervals (0.5–3 h) led to greater tumoral drug deposition and improved treatment outcomes, compared to longer drug–light intervals. At 2 mg/kg Dox, CPT with LC-Dox-PoP liposomes induced tumor regression and growth inhibition, whereas chemotherapy using several other formulations of Dox did not. LC-Dox-PoP liposomes were well tolerated at the 2 mg/kg dose.
中文翻译：
短暂的药物间隔可以改善携带MIA PaCa-2异种移植物的小鼠的脂质体化学疗法。
化学光疗（CPT）是一种新兴的肿瘤疗法，结合了光疗和化学疗法。长循环（LC）脂质体可以在双层中稳定地掺入2 mol％的卟啉-磷脂（PoP），并装载阿霉素（Dox）以生成LC-Dox-PoP脂质体，用于单剂CPT。向小鼠静脉内给药后，LC-Dox-PoP脂质体（2 mg / kg Dox）以典型的人类临床剂量DOXIL（50 mg / m 2）产生的相似血药浓度范围循环Dox）。这种给药方法旨在在携带皮下人胰腺MIA PaCa-2异种移植物的小鼠中获得生理相关的Dox和PoP浓度以及CPT血管反应。根据实验数据，用2 mg / kg LC-Dox-PoP进行光处理可诱导血管通透化，导致药代动力学模型估计的Dox肿瘤流入量增加12.5倍。与更长的药物-光疗间隔相比，更短的药物-光疗间隔（0.5-3小时）可导致更大的肿瘤药物沉积并改善治疗效果。在2 mg / kg Dox时，带有LC-Dox-PoP脂质体的CPT诱导了肿瘤消退和生长抑制，而使用Dox的其他几种制剂的化学疗法则没有。LC-Dox-PoP脂质体在2 mg / kg剂量下具有良好的耐受性。
更新日期：2018-04-02
中文翻译：
短暂的药物间隔可以改善携带MIA PaCa-2异种移植物的小鼠的脂质体化学疗法。
化学光疗（CPT）是一种新兴的肿瘤疗法，结合了光疗和化学疗法。长循环（LC）脂质体可以在双层中稳定地掺入2 mol％的卟啉-磷脂（PoP），并装载阿霉素（Dox）以生成LC-Dox-PoP脂质体，用于单剂CPT。向小鼠静脉内给药后，LC-Dox-PoP脂质体（2 mg / kg Dox）以典型的人类临床剂量DOXIL（50 mg / m 2）产生的相似血药浓度范围循环Dox）。这种给药方法旨在在携带皮下人胰腺MIA PaCa-2异种移植物的小鼠中获得生理相关的Dox和PoP浓度以及CPT血管反应。根据实验数据，用2 mg / kg LC-Dox-PoP进行光处理可诱导血管通透化，导致药代动力学模型估计的Dox肿瘤流入量增加12.5倍。与更长的药物-光疗间隔相比，更短的药物-光疗间隔（0.5-3小时）可导致更大的肿瘤药物沉积并改善治疗效果。在2 mg / kg Dox时，带有LC-Dox-PoP脂质体的CPT诱导了肿瘤消退和生长抑制，而使用Dox的其他几种制剂的化学疗法则没有。LC-Dox-PoP脂质体在2 mg / kg剂量下具有良好的耐受性。
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