Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo.
Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo.
复制标题
DOI：
10.1016/j.bcp.2009.09.003
复制
发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
--
作者：
Anand, Preetha;Nair, Hareesh B.;Sung, Bokyung;Kunnumakkara, Ajaikumar B.;Yadav, Vivek R.;Tekmal, Rajeshwar R.;Aggarwal, Bharat B.
姜黄素是一种存在于香料姜黄（Curcuma longa）中的黄色色素，与抗氧化剂、抗炎、抗增殖、抗癌、抗糖尿病、抗风湿和抗病毒作用有关，但其最佳潜力受到其在水溶剂中缺乏溶解度和口服生物利用度差的限制。我们采用了基于聚合物的纳米颗粒方法来提高生物利用度。姜黄素以97.5%的效率包封在基于聚（丙交酯-共-乙交酯）（PLGA）和稳定剂聚乙二醇（PEG）-5000的生物可降解纳米颗粒制剂中。动态激光光散射和透射电子显微镜表明粒径为80.9 nm。该姜黄素，从这里更名为“姜黄素（NP）”，其特征在于其生物活性。在体外姜黄素（NP）表现出非常快速（2小时vs > 72小时）和更有效的细胞摄取姜黄素。雌酶染色显示姜黄素（NP）在诱导白血病细胞凋亡和抑制各种肿瘤细胞系增殖方面至少与姜黄素一样有效或比姜黄素更有效。凝胶电泳迁移率实验表明，姜黄素（NP）在抑制TNF诱导的NF-κB活化和抑制NF-κ B调节的细胞增殖（cyclin D1）、侵袭（MMP-9）和血管生成（VEGF）蛋白方面比姜黄素更有效。在小鼠中，姜黄素（NP）比姜黄素具有更高的生物利用度和更长的半衰期。总之，我们证明了姜黄素负载的PLGA纳米颗粒制剂具有增强的细胞摄取，增加的体外生物活性和优于姜黄素的体内生物利用度。
Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with antioxidant, anti-inflammatory, anti-proliferative, anticancer, antidiabetic, antirheumatic, and antiviral effects, but its optimum potential is limited by its lack of solubility in aqueous solvents and poor oral bioavailability. We employed a polymer-based nanoparticle approach to improve bioavailability. Curcumin was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 80.9 nm. This curcumin, renamed from hereon “as curcumin (NP)”, was characterized for its biological activity. In vitro curcumin (NP) exhibited very rapid (2 h vs > 72 h) and more efficient cellular uptake then curcumin. Estrase staining revealed that curcumin (NP) was at least as potent as or more potent than curcumin in inducing apoptosis of leukemic cells and in suppressing proliferation of various tumor cell lines. When examined by electrophoretic gel shift mobility assay, curcumin (NP) was more active than curcumin in inhibiting TNF-induced NF-κB activation and in suppression of NF-κB-regulated proteins involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). In mice, curcumin (NP) was more bioavailable and had a longer half-life than curcumin. Overall we demonstrate that curcumin-loaded PLGA nanoparticles formulation has enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo over curcumin.
登录
查看更多内容
DOI：
10.1016/j.biocel.2008.06.010
发表时间：
2009-01
影响因子：
4
作者：
Aggarwal, Bharat B.;Harikumar, Kuzhuvelil B.
通讯作者：
Harikumar, Kuzhuvelil B.
影响因子：
1.8
作者：
Ma, Zengshuan;Shayeganpour, Anooshirvan;Samuel, John
通讯作者：
Samuel, John
影响因子：
11.5
作者：
Kim, TY;Kim, DW;Bang, YJ
通讯作者：
Bang, YJ
影响因子：
4.5
作者：
Salmaso, Stefano;Bersani, Sara;Caliceti, Paolo
通讯作者：
Caliceti, Paolo
影响因子：
10.2
作者：
Bisht S;Feldmann G;Soni S;Ravi R;Karikar C;Maitra A;Maitra A
通讯作者：
Maitra A