Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.
Drug Dev Ind Pharm. 2012 Sep;38(9):1107-16. doi: 10.3109/03639045.2011.641562. Epub 2012 Feb 20.
The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.
In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.
NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.
NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.
The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.
环氧化酶-2（COX-2）抑制剂在癌症化学预防中起着重要作用。某些 COX-2 抑制剂对癌细胞具有抗增殖和促凋亡作用。
本研究将美洛昔康（一种烯醇酸型选择性 COX-2 抑制剂）包封于聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米粒（NPs）中，以维持局部高浓度，并确定其疗效。
采用盐析和乳化蒸发步骤制备 NPs。考察了载药 NP 制剂的载药量、粒径、多分散指数、Zeta 电位、药物释放率和残留聚乙烯醇（PVA）百分比。考察了 PLGA 和 PVA 分子量变化对 NPs 理化性质的影响。评估了美洛昔康在 NPs 中的稳定性超过 3 个月。采用 COX-2 表达人结肠腺癌 HT-29 细胞系进行细胞摄取和活力测定。
NPs 呈球形，Zeta 电位为负，粒径在 170-231nm 之间，多分散指数较低。在 4°C 下，高分子量 PLGA 制备的 NPs 在三个月内表现出良好的物理稳定性。聚合物和乳化剂分子量的增加降低了 NPs 中美洛昔康的体外释放速率。美洛昔康载药 NPs 在 800µM 时对 HT-29 细胞表现出明显的细胞毒性作用。癌细胞对香豆素-6 载药 NPs 的摄取量较高。
本研究开发的 PLGA NPs 可能是美洛昔康治疗结肠癌的有效药物递送系统。
