Shavi Gopal Venkatesh, Nayak Usha Yogendra, Maliyakkal Naseer, Deshpande Praful Balavant, Raghavendra Ramesh, Kumar Averineni Ranjith, Reddya Meka Sreenivasa, Udupa Nayanabhirama, Shrawan B
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India; South Eastern Applied Material Research Centre (SEAM), WIT, Applied Technology Building, Waterford, Ireland.
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
Life Sci. 2015 Nov 15;141:143-55. doi: 10.1016/j.lfs.2015.09.021. Epub 2015 Sep 28.
Formulation and evaluation of anastrozole, an anti-cancer drug loaded in different biodegradable polymeric nanoparticles.
Different carrier systems such as poly(lactide-co-glycolide) (PLGA 50:50), poly(lactic-acid) (PLA) and poly(ε-caprolactone) (PCL) are used to prepare nanoparticles by simple emulsion technique. The surfactants polyvinyl alcohol and sodium deoxycholate were studied for their use as stabilizing agents at varying concentrations. The formulations were studied for their particle size, zeta potential, entrapment efficiency and solid state characteristics, and also were tested for their in vitro cytotoxicity and in vivo behavior in rats.
The entrapment ranged from 35 to 85%, depending on the drug-polymer ratio used. Particle size ranged from 100 to 350nm with optimal zeta potential. Accordingly, discrete spherical nanoparticles with smooth surface were obtained as evidence from Field Emission Scanning Electron Microscopy (FESEM) study. The solid state characteristics revealed dispersion of drug at the molecular level in the polymeric matrix of nanoparticles. A non-Fickian transport with initial burst release followed by slow release was observed with nanoparticles. The remarkable decrease in cell viability at various time points was observed for PLGA nanoparticles compared to other polymer matrices. The AUC(0→∞) of PLGA, PLA and PCL nanoparticles were found to be 4.77, 19.31 and 19.81 fold higher than (p<0.05) anastrozole in solution, respectively. Also, pharmacokinetics study revealed the long time circulation of anastrozole loaded polymeric nanoparticles.
The results suggest that developed nanoparticles could be used successfully for effective management of breast cancer chemotherapy.
制备并评估载有抗癌药物阿那曲唑的不同可生物降解聚合物纳米粒。
采用聚（丙交酯-乙交酯）（PLGA 50:50）、聚乳酸（PLA）和聚己内酯（PCL）等不同载体系统，通过简单乳液技术制备纳米粒。研究了不同浓度的聚乙烯醇和脱氧胆酸钠作为稳定剂的使用情况。对制剂的粒径、zeta电位、包封率和固态特性进行了研究，并对其体外细胞毒性和大鼠体内行为进行了测试。
包封率在35%至85%之间，取决于所用的药物-聚合物比例。粒径范围为100至350nm，具有最佳的zeta电位。因此，场发射扫描电子显微镜（FESEM）研究表明获得了表面光滑的离散球形纳米粒。固态特性显示药物在纳米粒的聚合物基质中以分子水平分散。纳米粒观察到非Fickian转运，初始有突释随后缓慢释放。与其他聚合物基质相比，PLGA纳米粒在各个时间点观察到细胞活力显著下降。PLGA、PLA和PCL纳米粒的AUC(0→∞)分别比溶液中的阿那曲唑高4.77、19.31和19.81倍（p<0.05）。此外，药代动力学研究表明载有阿那曲唑的聚合物纳米粒具有长时间循环。
结果表明，所开发的纳米粒可成功用于乳腺癌化疗的有效管理。
