Preparation and characterization of co-delivery of doxorubicin and elacridar in nanoparticles
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摘要: 目的 建立药物测定方法，并制备共载阿霉素和依克立达的PLGA纳米粒。 方法 利用紫外分光光度法（UV）和高效液相色谱法（HPLC）分别建立阿霉素和依克立达的测定方法；采用纳米沉淀法制备共载纳米粒，通过调节两药的投药比，优化处方，考察纳米粒的粒径、形态、包封率、载药量以及体外释放。 结果 阿霉素在1~40 μg/ml浓度范围内线性关系良好，标准曲线回归方程为A=0.021C+0.002，r=0.999 5； 依克立达在0.5~100 μg/ml浓度范围内线性关系良好，标准曲线回归方程为A=120 742.462 6C+1 974.570 4，r=1.000 0；通过处方优化，共载纳米粒的粒径约为50 nm，分布均一，呈圆形，阿霉素和依克立达的包封率分别为56.58%、51.66%，载药量分别为1.48%、1.85%，两药摩尔比约为1：1；体外释放缓慢。 结论 分别建立了方便快捷、结果准确、重复性好的阿霉素和依克立达的检测方法，并且制备了分散性好、粒径较小的纳米粒，为后续实验提供基础。Abstract: Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar. Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively; co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release. Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm; transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1:1;the nanoparticles released slowly in vitro. Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.
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Key words:
- doxorubicin /
- elacridar /
- nanoparticles /
- UV /
- HPLC
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[1] Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells[J]. Nature, 2001,414(6859):105-111. [2] Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening[J]. Cell, 2009, 138(4):645-659. [3] Cojoc M, Mäbert K, Muders MH, et al. A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms[J]. Semin Cancer Biol, 2014, 31:16-27. [4] Hubensack M, Müller C, Höcherl P, et al. Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice[J]. J Cancer Res Clin Oncol, 2008, 134(5): 597-607. [5] Karla PK, Earla R, Boddu SH, et al. Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells[J]. Curr Eye Res, 2009, 34(1): 1-9. [6] Nieto Montesinos RM, Beduneau A, Lamprecht A, et al. Liposomes co-loaded with elacridar and tariquidar to modulate the P-glycoprotein at the blood-brain barrier[J]. Mol Pharm, 2015, 12(11):3829-3838. [7] Wong HL, Bendayan R, Rauth AM, et al. Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new polymer-lipid hybrid nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer[J]. J Control Release, 2006, 116(3):275-284. [8] Singh MS, Lamprecht A. Cargoing P-gp inhibitors via nanoparticle sensitizes tumor cells against doxorubicin[J]. Int J Pharm, 2015, 478(2):745-752. [9] Planting AST,Sonneveld P,Gaast AVD,et al.A phase I and pharmacologic study of the MDR converter GF120918 in combination with doxorubicin in patients with advanced solid tumors[J].Cancer Chemother Pharmacol,2005,55(1):91-99. [10] Cheng J, Teply BA, Sherifi I, et al. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery[J]. Biomaterials, 2007, 28(5):869-876. [11] Zhu H, Chen H, Zeng X, et al. Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance[J]. Biomaterials, 2013, 35(7):2391-2400. -
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