Combinatorial delivery of Crizotinib-Palbociclib-Sildenafil using TPGS-PLA micelles for improved cancer treatment

被引：51

作者：

de Melo-Diogo, Duarte ^{[1
]}

Gaspar, Vitor M. ^{[1
]}

Costa, Elisabete C. ^{[1
]}

Moreira, Andre F. ^{[1
]}

Oppolzer, David ^{[1
]}

Gallardo, Eugenia ^{[1
]}

Correia, Ilidio J. ^{[1
]}

机构：

[1] CICS UBI, P-6200506 Covilha, Portugal

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2014年 / 88卷 / 03期

关键词：

Cancer; Co-delivery; Micellar carriers; Multidrug therapy; Non-small cell lung cancer; TPGS-PLA copolymer; VITAMIN-E TPGS; CO-DELIVERY; CELLULAR UPTAKE; DRUG-DELIVERY; POLYMERIC NANOPARTICLES; COPOLYMER; SUCCINATE; FORMULATION; DOCETAXEL; EFFICACY;

D O I：

10.1016/j.ejpb.2014.09.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The co-delivery of multiple chemotherapeutics by micellar delivery systems is a valuable approach to improve cancer treatment since various disease hallmarks can be targeted simultaneously. However, the delivery of multiple drugs requires a nanocarrier structure that can encapsulate various bioactive molecules. In this study, we evaluate the simultaneous encapsulation of a novel triple drug combination in D-alpha-tocopheryl polyethylene glycol 1000 succinate-poly(lactic acid) (TPGS-PLA) amphiphilic micelles for cancer therapy. The drug mixture involves two anti-tumoral drugs, Crizotinib and Palbociclib combined with Sildenafil, a compound that is capable of increasing drug accumulation in the intracellular compartment. Such combination aims to achieve an enhanced cytotoxic effect in cancer cells. Our results demonstrated that TPGS-PLA copolymers self-assembled into stable nanosized micelles (158.3 nm) capable of co-encapsulating the three drugs with high loading efficiency. Triple drug loaded TPGS-PLA micelles were internalized in A549 non-small lung cancer cells and exhibited an improved cytotoxic effect in comparison with single (Crizotinib) or dual (Crizotinib-Palbociclib) drug loaded micelles, indicating the therapeutic potential of the triple co-delivery strategy. These findings demonstrate that TPGS-PLA micelles are suitable carriers for multiple drug delivery and also that this particular drug combination may have potential to improve cancer treatment. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：718 / 729

页数：12

共 55 条

[1] On the determination of the critical micelle concentration by the pyrene 1:3 ratio method [J].