Tumor stromal disrupting agent enhances the anticancer efficacy of docetaxel loaded PEGylated liposomes in lung cancer

被引:47
作者
Patel, Ketan [1 ]
Doddapaneni, Ravi [1 ]
Chowdhury, Nusrat [1 ]
Boakye, Cedar H. A. [1 ]
Behl, Gautam [1 ]
Singh, Mandip [1 ]
机构
[1] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA
基金
美国国家卫生研究院;
关键词
cancer nanomedicine; docetaxel; orthotopic lung cancer; pegylated liposome; solid tumor targeting; tumor fibrosis; tumor stroma; ANTITUMOR-ACTIVITY; DRUG-DELIVERY; TGF-BETA; INHALATION DELIVERY; IN-VITRO; NANOPARTICLES; CYTOTOXICITY; PACLITAXEL; INHIBITION; CARCINOMA;
D O I
10.2217/nnm.16.37
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: Therapeutic efficacy of anticancer nanomedicine is compromised by tumor stromal barriers. The present study deals with the development of docetaxel loaded PEGylated liposomes (DTXPL) and to investigate the effect of tumor stroma disrupting agent, telmisartan, on anticancer efficacy of DTXPL. Methods: DTXPL was prepared using proprietary modified hydration method. Effect of oral telmisartan treatment on tumor uptake of coumarin-6 liposomes and anticancer efficacy of DTXPL was evaluated in orthotopic xenograft lung tumor bearing mice. Results: DTXPL (105.7 l +/- 3.8 nm) showed very high physical stability, negligible hemolysis, 428% enhancement in bioavailability with significantly higher intratumoral uptake. Marked reduction in collagen-I, MMP2/9 and lung tumor weight were observed in DTXPL+telmisartan group. Conclusion: Combination of DTXPL with telmisartan could significantly enhance clinical outcome in lung cancer.
引用
收藏
页码:1377 / 1392
页数:16
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