Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid.
Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid.
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DOI：
10.1586/14737140.2015.1000868
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发表时间：
2015-02
影响因子：
3.3
通讯作者：
Ferreira LA
中科院分区：
文献类型：
--
作者：
Silva EL;Carneiro G;Caetano PA;Goulart G;Ferreira Costa D;de Souza-Fagundes EM;Gomes DA;Ferreira LA
全反式维甲酸（ATRA）是分化剂和组蛋白脱乙酰酶抑制剂（如三丁酸甘油酯（TB））的最成功的实例之一，已知其抗肿瘤活性和增强药物（如ATRA）的作用。纳米结构脂质载体（NLC）代表了一种有前途的替代亲脂性药物，如ATRA的封装。本研究旨在开发、表征和评估用于癌症治疗的ATRA-TB负载纳米结构脂质载体（NLC）的细胞毒性。原位形成的离子配对之间的ATRA和亲脂性胺（苯乙苄胺; BNT）的NLC的特性（大小，zeta电位，封装效率）的影响进行了评价。三丁酸甘油酯（TB），丁酸供体，被用作脂质基质的组分。评价了MCF-7、MDA-MB-231、HL-60和Jurkat细胞系对细胞活力和细胞周期时相分布的体外活性。胺的存在显著增加了ATRA在NLC中的包封率。TB-ATRA负载的NLC对细胞活力的抑制比游离药物更明显。细胞周期时相分布的分析也显示TB-ATRA负载的NLC的活性增加，在G 0/G1期转变中具有明显的细胞周期阻滞效果。TB的存在在制剂的活性中起重要作用。总之，这些研究结果表明，TB-ATRA负载的NLC代表了一种有前途的替代静脉注射ATRA治疗癌症。
All-trans retinoic acid (ATRA) is one of the most successful examples of differentiation agents and histone deacetylase inhibitors, such as tributyrin (TB), are known for their antitumor activity and potentiating action of drugs such as ATRA. Nanostructured lipid carriers (NLC) represent a promising alternative to the encapsulation of lipophilic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of ATRA-TB-loaded nanostructured lipid carriers (NLC) for cancer treatment. The influence of in situ formation of an ion pairing between ATRA and a lipophilic amine (benethamine; BNT) on the characteristics of NLC (size, zeta potential, encapsulation efficiency) was evaluated. Tributyrin (TB), a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for MCF-7, MDA-MB-231, HL-60, and Jurkat cell lines. The presence of the amine significantly increased the encapsulation efficiency of ATRA in NLC. Inhibition of cell viability by TB-ATRA-loaded NLC was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for TB-ATRA-loaded NLC, with the clear effect of cell cycle arrest in G0/G1 phase transition. The presence of TB played an important role in the activity of the formulation. Taken together, these findings suggest that TB-ATRA-loaded NLC represent a promising alternative to intravenous administration of ATRA in cancer treatment.