Khuroo Tahir, Verma Devina, Talegaonkar Sushama, Padhi Santwana, Panda Amulya K, Iqbal Zeenat
Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India; Product Development Cell-II, National Institute of Immunology, New Delhi 110067, India; Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Limited, Gurgaon 122015, Haryana, India.
Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Int J Pharm. 2014 Oct 1;473(1-2):384-94. doi: 10.1016/j.ijpharm.2014.07.022. Epub 2014 Jul 19.
The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in vitro release study the release of drugs from TOP-TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells.
开发了同时负载盐酸拓扑替康（TOP）和柠檬酸他莫昔芬（TAM）的双药聚（聚乳酸-乙醇酸）（PLGA(1)）纳米颗粒（TOP-TAM NPs(2)），通过增强TOP在肠道和乳腺细胞中的渗透来实现协同治疗乳腺癌。TAM作为P-糖蛋白（P-gp(5)）抑制剂，通过降低剂量减少了单一药物的副作用。纳米颗粒采用双乳液（w/o/w）法制备。使用扫描电子显微镜（SEM(6)）和透射电子显微镜（TEM(7)）技术发现，优化后的TOP-TAM NPs具有光滑的球形形态。同样，纳米颗粒的尺寸为151.2±1.6 nm，多分散指数（PDI(8)）为0.147±0.03。TAM和TOP的包封率分别为95.17±3.57%和57.77±2.2%。差示扫描量热法（DSC(9)）下冻干的纳米颗粒显示TOP和TAM均为无定形性质。体外释放研究发现，TOP-TAM NPs中的药物释放遵循Higuchi模式。体外肠道渗透研究表明，TAM增强了TOP的渗透，并使其生物利用度提高了1.9倍。通过对MCF-7细胞进行细胞系研究，进一步证实了药物组合的渗透和活性。
