Pharmacokinetics and biodistribution of lonidamine/paclitaxel loaded, EGFR-targeted nanoparticles in an orthotopic animal model of multi-drug resistant breast cancer.
Pharmacokinetics and biodistribution of lonidamine/paclitaxel loaded, EGFR-targeted nanoparticles in an orthotopic animal model of multi-drug resistant breast cancer.
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DOI：
10.1016/j.nano.2010.12.009
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发表时间：
2011-08
影响因子：
5.4
通讯作者：
Amiji, Mansoor
中科院分区：
文献类型：
--
作者：
Milane, Lara;Duan, Zhen-feng;Amiji, Mansoor
本研究的目的是评估与抗癌药物氯尼达明和紫杉醇装载的表皮生长因子受体（EGFR）靶向聚合物共混物纳米粒的生物分布和药代动力学。在多药耐药（MDR）乳腺癌的原位动物模型中定量血浆、肿瘤和组织分布概况，并与用非靶向纳米颗粒的治疗和用药物溶液的治疗进行比较。合成了聚（D，L-丙交酯-共-乙交酯）/聚（乙二醇）/EGFR靶向肽（PLGA/PEG/EFGR peptide）构建体，用于掺入聚（ε-己内酯）（PCL）颗粒中以实现EGFR主动靶向。开发了等度HPLC方法来定量小鼠血浆、肿瘤和重要器官中的氯尼达明和紫杉醇。靶向纳米颗粒表现出相对于药物溶液和非靶向纳米颗粒的上级药代动力学特征，特别是对于氯尼达明递送。蓄积的第一个靶部位是肝脏，其次是肾脏，然后是肿瘤块;最大肿瘤蓄积发生在给药后3小时。通过EGFR靶向聚合物共混物纳米载体给药的氯尼达明/紫杉醇联合治疗可能成为未来治疗MDR癌症的可行平台。
The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multi-drug resistant (MDR) breast cancer and were compared to treatment with non-targeted nanoparticles and to treatment with drug solution. Poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/EGFR targeting peptide (PLGA/PEG/EFGR peptide) construct was synthesized for incorporation in poly(ε-caprolactone) (PCL) particles to achieve active EGFR targeting. An isocratic HPLC method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated superior pharmacokinetic profile relative to drug solution and non-targeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation is the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occurs at 3 hours post-administration. Lonidamine/paclitaxel combination therapy administered via EGFR-targeted polymer blend nanocarriers may become a viable platform for the future treatment of MDR cancer.
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影响因子：
4.9
作者：
Ganta, Srinivas;Amiji, Mansoor
通讯作者：
Amiji, Mansoor
影响因子：
4.9
作者：
Milane L;Duan Z;Amiji M
通讯作者：
Amiji M
影响因子：
4.8
作者：
Li, ZH;Zhao, RJ;Gu, JR
通讯作者：
Gu, JR
影响因子：
5.8
作者：
Chawla, JS;Amiji, MM
通讯作者：
Amiji, MM
DOI：
10.1016/s0889-8588(18)30095-9
发表时间：
1995-04-01
影响因子：
2.4
作者：
LEIGHTON, JC;GOLDSTEIN, LJ
通讯作者：
GOLDSTEIN, LJ