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Recherche en cancérologie

纳米颗粒对荷瘤小鼠药相结合的样品提取及同时色谱定量分析

Published: October 05, 2017
doi:
10.3791/56159
, , , , , , ,
1Department of Pharmaceutical Sciences,University of Toronto, 2Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Ontario Cancer Institute,University Health Network

Summary

该协议描述了一个高效和方便的分析过程中的样品提取和同时测定多药, 阿霉素 (DOX), 丝裂霉 C (MMC) 和心脏毒性 DOX 代谢物, doxorubicinol (DOXol), 在生物样品的临床前乳腺癌模型治疗的纳米颗粒制剂的协同药物组合。

Abstract

联合化疗常用于肿瘤治疗的临床;然而, 与正常组织相关的不良反应可能会限制其治疗效果。纳米药物组合已被证明可以缓解问题的免费药物联合治疗。我们以前的研究表明, 两种抗癌药物, 阿霉素 (DOX) 和丝裂霉素 C (MMC) 的结合, 产生了对小鼠和人乳腺癌细胞的协同作用体外。DOX 和 MMC co-loaded 聚合物脂质杂交纳米颗粒 (DMPLN) 绕过各种外排转运泵, 赋予多药耐药性, 并证明了乳腺肿瘤模型的增强功效。与传统的溶液形式相比, 这种 DMPLN 的优越功效归因于 DOX 和 MMC 的同步药代动力学, 以及 nanocarrier PLN 所启用的肿瘤细胞内的细胞药物生物利用度的提高。

为了评价 co-administered DOX 和 MMC 在自由溶液和纳米颗粒中的药代动力学和生物分布, 采用反相高效液相色谱 (HPLC) 的简单高效的药物分析方法是开发.与以前报告的方法, 分别分析 DOX 或 mmc 在等离子体中, 这种新的 HPLC 法可以同时定量 DOX, mmc 和主要有氧 DOX 代谢物, doxorubicinol (DOXol), 在各种生物矩阵 (例如,全血, 乳腺肿瘤和心脏)。采用双荧光和紫外线吸收探针 4-伞形 (4 亩) 作为一个内部标准 (行列) one-step 检测多种药物分析不同的检测波长。该方法成功地应用于原位乳腺肿瘤小鼠模型中的全血和不同组织中纳米颗粒和溶液方法的 DOX 和 MMC 的浓度测定。所提出的分析方法是临床前分析药物组合纳米分娩的有效工具。

Introduction

化疗是许多癌症的主要治疗方式, 但它往往与严重的副作用和有限的功效, 由于耐药性和其他因素1,2,3。为了改善化疗的结果, 药物组合方案已在临床应用的考虑因素, 如不重叠的毒性, 不同的药物作用机制, 和非耐药性4,5,6. 在临床试验中, 与序贯药物传递的方案相比, 经常观察到肿瘤的反应率更高, 其方法是:7,8。然而, 由于游离药物形态的非最佳生物分布, 同时注射多种药物可引起明显的正常组织毒性, 超过治疗效果9,10,11。Nanocarrier-based 药物的传递已被证明改变药代动力学和生物分布的封装药物, 加强肿瘤靶向积累12,13,14。正如我们在最近的文章中所回顾的, 与协同药物组合的纳米 co-loaded 已经证明了能够减轻自由药物组合所遇到的问题, 由于其控制的时间和空间 co-delivery多种药物对肿瘤组织, 使协同药物对癌细胞的作用4,15,16。结果, 在临床前和临床医学研究中均表现出优异的治疗效果和低毒力4,17,18。

我们以前的体外研究发现, 两种抗癌药物, 阿霉素 (DOX) 和丝裂霉 C (mmc) 的结合, 产生了对几个乳腺癌细胞株的协同作用, 此外, co-loading DOX 和 mmc 在聚合物-脂质混合纳米颗粒 (DMPLN) 克服了各种耐药相关的外排泵 (例如, p-糖蛋白和抗乳腺癌蛋白)19,20,21。在体内, DMPLN 使 DOX 和 MMC 的空间颞 co-delivery 对肿瘤部位和癌症细胞内药物的生物利用度提高, 这表明 DOX 代谢产物 doxorubicinol (DOXol)22的形成是适度的。结果, DMPLN 增强肿瘤细胞凋亡, 抑制肿瘤生长, 延长宿主存活率, 与游离 DOX 和 MMC 组合物或脂质体 DOX 配方22,23,24, 25。

分析 nanocarrier co-delivered 药物的实际用量对于设计有效的纳米粒子配方是至关重要的。采用高效液相色谱 (HPLC) 单独或与质谱联用 (MS)26、27、28等方法, 对单 DOX 或 MMC 剂量的血浆水平进行了分析。,29,30,31,32,33,34. 然而, 这些方法往往是费时和不切实际的组合疗法, 因为大量的生物样品需要单独准备的分析多种药物 (有时包括药物代谢物)。除了强的血浆蛋白结合 DOX 和 MMC, 红细胞也有很大的能力绑定和集中许多抗癌药物35,36。因此, DOX 或 MMC 的等离子分析可能会混淆实际的血药浓度。本工作 (图 1) 描述了一种简单而稳健的多药分析方法, 采用反相高效液相色谱法同时提取和定量 DOX、MMC 和 DOX 代谢物 doxorubicinol (DOXol) 的全血和各种组织 (例如,肿瘤)。它已成功地应用于确定药物的药代动力学和生物分布的 DOX 和 MMC, 以及形成的 DOXol 后, 通过免费的解决方案或纳米颗粒 (即, DMPLN 和脂质体 DOX) 在原位植入小鼠乳腺肿瘤模型静脉注射后 (静脉注射)22。

Protocol

所有动物实验均由安大略省癌症研究所的大学卫生网络动物保育委员会批准, 并按照加拿大动物保育理事会的准则进行. 1. 生物样品制备 在静脉注射 (静脉注射) 药物制剂后, 在预定的时点上收集全血、主要脏器和乳腺肿瘤 (如 ,DMPLN, 脂质体 DOX) 用准备好的含药物的制剂注射乳房肿瘤的小鼠静脉注射. 麻醉在指定的时点 ( 如 , 1…

Representative Results

两种抗癌药物, DOX 和 MMC, 以及 DOX 代谢物, DOXol, 同时检测没有任何生物干扰在相同的应用梯度 HPLC 条件下使用4亩作为行列的荧光和紫外线探测器。DOX, mmc, DOXol 和4亩分离从彼此的保留时间为5.7 分钟的 MMC, 10.4 分钟 DOXol, 10.9 分钟4亩, 11.1 分钟 DOX (图 2)。全血和各种组织中的每种药物都显示了相关系数的浓度线性 (R2), 范围从0.98 到 1.00 (<…

Discussion

与其他能同时检测单一药物种类的色谱方法相比, 目前的 HPLC 协议能够同时定量三药物化合物 (DOX、MMC 和 DOXol) 在同一生物基质中, 无需改变移动阶段。这种制备和分析方法已成功地应用于确定两个纳米药物传递系统 (即脂质体 DOX 和 DMPLN) 的药代动力学和生物分布,22。由于乙二醇纳米颗粒可延长负载药物的全身循环, 从而在很长一段时间 (#62; 24 h) 中产生高血药浓度, ?…

Divulgations

The authors have nothing to disclose.

Acknowledgements

作者衷心感谢加拿大自然科学与工程研究理事会 ( NSERC ) 为高效液相色谱 , 加拿大卫生研究院 ( 研究院 ) 和加拿腺癌研究 ( CBCR ) 提供的手术补助金。加盟 x.y.z 吴, 和多伦多大学奖学金 R.X. 张和 t。

Materials

Doxorubicin  Polymed Theraeutics 111023 Anticancer drug
Mitomycin C Polymed Theraeutics 060814 Anticancer drug
Doxorubicinol (DOXol) Toronto Research Chemicals D558020 Metabolite of DOX
4-Methylumbelliferone sodium salt  Sigma-Aldrich M1508 Internal standard
Myristic Acid Sigma-Aldrich 544-63-8   Materials for poly-lipid hybrid nanoparticles
Polyoxyethylene (100) Stearate Spectrum M1402 Materials for poly-lipid hybrid nanoparticles
Polyoxyethylene (40) Stearate Sigma-Aldrich P3440 Materials for poly-lipid hybrid nanoparticles
Pluronic F68 (PF68) BASF Corp. 9003-11-6 Materials for poly-lipid hybrid nanoparticles
Ultrasonication (UP100H) Hielscher, Ultrasound Technology NA Nanoparticle preparation
Water Bath (ISOTEMP 3016HS) Fisher Scientific NA Nanoparticle preparation
Liposomal Doxorubicin  (Caelyx) Janssen Purchased from the pharmacy Princess Margaret Hospital Clinically-approved nanoparticle formulation 
HPLC-graded Methanol Caledon Chemicals 6701-7-40 HPLC mobile phase composition
HPLC-graded H2O Caledon Chemicals 8801-7-40 HPLC mobile phase composition
HPLC-graded Acetonitrile  Caledon Chemicals 1401-7-40 HPLC mobile phase composition
Trifluoroacetic Acid Sigma-Aldrich 302031 HPLC mobile phase composition
0.45 μm Nylon Membrane Filter Paper Whatman WHA7404004 HPLC mobile phase preparation
1cc Plastic Syringes Becton, Dickinson and Company 2606-309659 Treatment injection
5cc Plastic Syringes Becton, Dickinson and Company 2608-309646 Tissue collections
30G 1/2 Needles Becton, Dickinson and Company 305106 Treatment injection
25G 5/8 Needles Becton, Dickinson and Company 305122 Tissue collections
Sterile 0.9% Saline Univeristy of Toronto House Brand 1011 Tissue perfusion
13 ml Rounded-bottom conical tube  SARSTEDT 62.515.006 Prolyprolene, tissue homogenization
Alpha Minimum Essential Medium (MEM)  Gibco 12571063 Cell medium
1 x Phosphate Buffer Saline Gibco 10010023 Tissue homogenization
Triton X-100 Sigma-Aldrich X100-100 ML Tissue homogenization
Formic acid Caledon Chemicals 1/5/3840 Adjust pH for extraction solvent
Sodium heparin sprayed plastic tubes Becton, Dickinson and Company 367878 Blood collection
Analytical Weigh Balance  Sartorius  CPA225D NA
pH meters  Fisher Scientific 13-637-671 accumet BASIC
Vortex Mixter Fisher Scientific 02-215-365 Vortexing samples at desired speed
1.5 ml  Microcentrifuge Tube Fisherbrand 2043-05408129 Prolyprolene
Model 1000 homogenizer Fisher Scientific 08-451-672 Tissue homogenization
Centrifuge 5702R Eppendorf 5702R Extraction preparation
Heated Evaporator System Glas-Col NA Sample reconstitution
HPLC Screw Thread Vials DIKMA 5320 HPLC sample injection
HPLC Screw Caps with PTFE White Silicone Septa DIKMA 5325 HPLC sample injection
HPLC Polypropylene Insert   Agilent Technologies 5182-0549 Maximum volume 250 μl, HPLC sample injection
Xbridge C18 Column Waters Corporation 186003117 Drug analysis
Gradient pump  Waters Corporation W600 Drug analysis
Auto-sampler Waters Corporation W2707 Drug analysis
Photodiode array detector  Waters Corporation W2998 Drug analysis
Multi λ fluoresence detector  Waters Corporation W2475 Drug analysis
EMPOWER 2 Waters Corporation NA Data analysis software
Scientist Micromath NA Pharmacokinetic analysis
Female Balb/c Mice Jackson Laboratory 001026 In vivo
EMT6/WT Breast Cancer Cells Provided by Dr. Ian Tannock; Ontario Cancer Institute NA In vivo
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References

  1. Holohan, C., Van Schaeybroeck, S., Longley, D. B., Johnston, P. G. Cancer Drug Resistance: An Evolving Paradigm. Nat. Rev. Cancer. 13 (10), 714-726 (2013).
  2. Szakacs, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., Gottesman, M. M. Targeting Multidrug Resistance in Cancer. Nat Rev Drug Discov. 5 (3), 219-234 (2006).
  3. Kong, A. -. N. T., Kong, A. .. N. .. T. .. ,. . Inflammation, Oxidative Stress, and Cancer: Dietary Approaches for Cancer Prevention. , (2013).
  4. Zhang, R. X., Wong, H. L., Xue, H. Y., Eoh, J. Y., Wu, X. Y. Nanomedicine of Synergistic Drug Combinations for Cancer Therapy – Strategies and Perspectives. J Control Release. 240, 489-503 (2016).
  5. Webster, R. M. Combination Therapies in Oncology. Nat. Rev. Drug. Discov. 15 (2), 81-82 (2016).
  6. Waterhouse, D. N., Gelmon, K. A., Klasa, R., Chi, K., Huntsman, D., Ramsay, E., Wasan, E., Edwards, L., Tucker, C., Zastre, J., Wang, Y. Z., Yapp, D., Dragowska, W., Dunn, S., Dedhar, S., Bally, M. B. Development and Assessment of Conventional and Targeted Drug Combinations for Use in the Treatment of Aggressive Breast Cancers. Curr Cancer Drug Targets. 6 (6), 455-489 (2006).
  7. Cancello, G., Bagnardi, V., Sangalli, C., Montagna, E., Dellapasqua, S., Sporchia, A., Iorfida, M., Viale, G., Barberis, M., Veronesi, P., Luini, A., Intra, M., Goldhirsch, A., Colleoni, M. Phase Ii Study with Epirubicin, Cisplatin, and Infusional Fluorouracil Followed by Weekly Paclitaxel with Metronomic Cyclophosphamide as a Preoperative Treatment of Triple-Negative Breast Cancer. Clin Breast Cancer. 15 (4), 259-265 (2015).
  8. Masuda, N., Higaki, K., Takano, T., Matsunami, N., Morimoto, T., Ohtani, S., Mizutani, M., Miyamoto, T., Kuroi, K., Ohno, S., Morita, S., Toi, M. A Phase Ii Study of Metronomic Paclitaxel/Cyclophosphamide/Capecitabine Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide as Preoperative Chemotherapy for Triple-Negative or Low Hormone Receptor Expressing/Her2-Negative Primary Breast Cancer. Cancer Chemother Pharmacol. 74 (2), 229-238 (2014).
  9. Carrick, S., Parker, S., Thornton, C. E., Ghersi, D., Simes, J., Wilcken, N. Single Agent Versus Combination Chemotherapy for Metastatic Breast Cancer. Cochrane Database Syst Rev. 15 (2), 003372 (2009).
  10. Cardoso, F., Bedard, P. L., Winer, E. P., Pagani, O., Senkus-Konefka, E., Fallowfield, L. J., Kyriakides, S., Costa, A., Cufer, T., Albain, K. S., Force, E. -. M. T. International Guidelines for Management of Metastatic Breast Cancer: Combination Vs Sequential Single-Agent Chemotherapy. J Natl Cancer Inst. 101 (17), 1174-1181 (2009).
  11. Alba, E., Martin, M., Ramos, M., Adrover, E., Balil, A., Jara, C., Barnadas, A., Fernandez-Aramburo, A., Sanchez-Rovira, P., Amenedo, M., Casado, A. Multicenter Randomized Trial Comparing Sequential with Concomitant Administration of Doxorubicin and Docetaxel as First-Line Treatment of Metastatic Breast Cancer: A Spanish Breast Cancer Research Group (Geicam-9903) Phase Iii. J Clinn Oncol. 22 (13), 2587-2593 (2004).
  12. Sadat, S. M., Saeidnia, S., Nazarali, A. J., Haddadi, A. Nano-Pharmaceutical Formulations for Targeted Drug Delivery against Her2 in Breast Cancer. Curr. Cancer Drug Targets. 15 (1), 71-86 (2015).
  13. Devadasu, V. R., Wadsworth, R. M., Ravi Kumar, M. N. V. Tissue Localization of Nanoparticles Is Altered Due to Hypoxia Resulting in Poor Efficacy of Curcumin Nanoparticles in Pulmonary Hypertension. Eur. J. Pharm. Biopharm. 80 (3), 578-584 (2012).
  14. Li, S. D., Huang, L. Pharmacokinetics and Biodistribution of Nanoparticles. Mol. Pharm. 5 (4), 496-504 (2008).
  15. Zhang, R. X., Ahmed, T., Li, L. Y., Li, J., Abbasi, A. Z., Wu, X. Y. Design of Nanocarriers for Nanoscale Drug Delivery to Enhance Cancer Treatment Using Hybrid Polymer and Lipid Building Blocks. Nanoscale. 9 (4), 1334-1355 (2017).
  16. Wang, X., Li, S., Shi, Y., Chuan, X., Li, J., Zhong, T., Zhang, H., Dai, W., He, B., Zhang, Q. The Development of Site-Specific Drug Delivery Nanocarriers Based on Receptor Mediation. J. Control. Release. 193, 139-153 (2014).
  17. Batist, G., Gelmon, K. A., Chi, K. N., Miller, W. H., Chia, S. K., Mayer, L. D., Swenson, C. E., Janoff, A. S., Louie, A. C. Safety, Pharmacokinetics, and Efficacy of Cpx-1 Liposome Injection in Patients with Advanced Solid Tumors. Clin Cancer Res. 15 (2), 692-700 (2009).
  18. Mayer, L. D., Harasym, T. O., Tardi, P. G., Harasym, N. L., Shew, C. R., Johnstone, S. A., Ramsay, E. C., Bally, M. B., Janoff, A. S. Ratiometric Dosing of Anticancer Drug Combinations: Controlling Drug Ratios after Systemic Administration Regulates Therapeutic Activity in Tumor-Bearing Mice. Mol. Cancer Ther. 5 (7), 1854-1863 (2006).
  19. Prasad, P., Cheng, J., Shuhendler, A., Rauth, A. M., Wu, X. Y. A Novel Nanoparticle Formulation Overcomes Multiple Types of Membrane Efflux Pumps in Human Breast Cancer Cells. Drug Deliv Transl Res. 2 (2), 95-105 (2012).
  20. Shuhendler, A. J., Cheung, R. Y., Manias, J., Connor, A., Rauth, A. M., Wu, X. Y. A Novel Doxorubicin-Mitomycin C Co-Encapsulated Nanoparticle Formulation Exhibits Anti-Cancer Synergy in Multidrug Resistant Human Breast Cancer Cells. Breast Cancer Res Treat. 119 (2), 255-269 (2010).
  21. Shuhendler, A. J., O’Brien, P. J., Rauth, A. M., Wu, X. Y. On the Synergistic Effect of Doxorubicin and Mitomycin C against Breast Cancer Cells. Drug Metabol. Drug Interact. 22 (4), 201-233 (2007).
  22. Zhang, R. X., Cai, P., Zhang, T., Chen, K., Li, J., Cheng, J., Pang, K. S., Adissu, H. A., Rauth, A. M., Wu, X. Y. Polymer-Lipid Hybrid Nanoparticles Synchronize Pharmacokinetics of Co-Encapsulated Doxorubicin-Mitomycin C and Enable Their Spatiotemporal Co-Delivery and Local Bioavailability in Breast Tumor. Nanomedicine. 12 (5), 1279-1290 (2016).
  23. Zhang, T., Prasad, P., Cai, P., He, C., Shan, D., Rauth, A. M., Wu, X. Y. Dual-Targeted Hybrid Nanoparticles of Synergistic Drugs for Treating Lung Metastases of Triple Negative Breast Cancer in Mice. Acta Pharmacol Sin. , 1-13 (2017).
  24. Shuhendler, A. J., Prasad, P., Zhang, R. X., Amini, M. A., Sun, M., Liu, P. P., Bristow, R. G., Rauth, A. M., Wu, X. Y. Synergistic Nanoparticulate Drug Combination Overcomes Multidrug Resistance, Increases Efficacy, and Reduces Cardiotoxicity in a Nonimmunocompromised Breast Tumor Model. Mol Pharm. 11 (8), 2659-2674 (2014).
  25. Prasad, P., Shuhendler, A., Cai, P., Rauth, A. M., Wu, X. Y. Doxorubicin and Mitomycin C Co-Loaded Polymer-Lipid Hybrid Nanoparticles Inhibit Growth of Sensitive and Multidrug Resistant Human Mammary Tumor Xenografts. Cancer Lett. 334 (2), 263-273 (2013).
  26. Rafiei, P., Michel, D., Haddadi, A. Application of a Rapid Esi-Ms/Ms Method for Quantitative Analysis of Docetaxel in Polymeric Matrices of Plga and Plga-Peg Nanoparticles through Direct Injection to Mass Spectrometer. Am. J. Anal. Chem. 6 (2), 164-175 (2015).
  27. Daeihamed, M., Haeri, A., Dadashzadeh, S. A Simple and Sensitive Hplc Method for Fluorescence Quantitation of Doxorubicin in Micro-Volume Plasma: Applications to Pharmacokinetic Studies in Rats. Iran. J. Pharm. Res. 14, 33-42 (2015).
  28. Alhareth, K., Vauthier, C., Gueutin, C., Ponchel, G., Moussa, F. Hplc Quantification of Doxorubicin in Plasma and Tissues of Rats Treated with Doxorubicin Loaded Poly(Alkylcyanoacrylate) Nanoparticles. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 887-888, 128-132 (2012).
  29. Al-Abd, A. M., Kim, N. H., Song, S. C., Lee, S. J., Kuh, H. J. A Simple Hplc Method for Doxorubicin in Plasma and Tissues of Nude Mice. Arch Pharm Res. 32 (4), 605-611 (2009).
  30. Loadman, P. M., Calabrese, C. R. Separation Methods for Anthraquinone Related Anti-Cancer Drugs. J. Chromatogr. B Biomed. Sci. Appl. 764 (1-2), 193-206 (2001).
  31. Zhang, Z. D., Guetens, G., De Boeck, G., Van Cauwenberghe, K., Maes, R. A., Ardiet, C., van Oosterom, A. T., Highley, M., de Bruijn, E. A., Tjaden, U. R. Simultaneous Determination of the Peptide-Mitomycin Kw-2149 and Its Metabolites in Plasma by High-Performance Liquid Chromatography. J. Chromatogr. B Biomed. Sci. Appl. 739 (2), 281-289 (2000).
  32. Alvarez-Cedron, L., Sayalero, M. L., Lanao, J. M. High-Performance Liquid Chromatographic Validated Assay of Doxorubicin in Rat Plasma and Tissues. J. Chromatogr. B Biomed. Sci. Appl. 721 (2), 271-278 (1999).
  33. Paroni, R., Arcelloni, C., De Vecchi, E., Fermo, I., Mauri, D., Colombo, R. Plasma Mitomycin C Concentrations Determined by Hplc Coupled to Solid-Phase Extraction. Clin. Chem. 43 (4), 615-618 (1997).
  34. Song, D., Au, J. L. Direct Injection Isocratic High-Performance Liquid Chromatographic Analysis of Mitomycin C in Plasma. J Chromatogr B Biomed Appl. 676 (1), 165-168 (1996).
  35. Schrijvers, D. Role of Red Blood Cells in Pharmacokinetics of Chemotherapeutic Agents. Clin. Pharmacokinet. 42 (9), 779-791 (2003).
  36. Colombo, T., Broggini, M., Garattini, S., Donelli, M. G. Differential Adriamycin Distribution to Blood Components. Eur. J. Drug Metab. Pharmacokinet. 6 (2), 115-122 (1981).
  37. Maeda, H., Nakamura, H., Fang, J. The Epr Effect for Macromolecular Drug Delivery to Solid Tumors: Improvement of Tumor Uptake, Lowering of Systemic Toxicity, and Distinct Tumor Imaging in Vivo. Adv. Drug Deliv. Rev. 65 (1), 71-79 (2013).
  38. Gustafson, D. L., Rastatter, J. C., Colombo, T., Long, M. E. Doxorubicin Pharmacokinetics: Macromolecule Binding, Metabolism, and Excretion in the Context of a Physiologic Model. J. Pharm. Sci. 91 (6), 1488-1501 (2002).
  39. Gabizon, A., Shiota, R., Papahadjopoulos, D. Pharmacokinetics and Tissue Distribution of Doxorubicin Encapsulated in Stable Liposomes with Long Circulation Times. J. Natl. Cancer Inst. 81 (19), 1484-1488 (1989).
  40. Motlagh, N. S., Parvin, P., Ghasemi, F., Atyabi, F. Fluorescence Properties of Several Chemotherapy Drugs: Doxorubicin, Paclitaxel and Bleomycin. Biomed Opt Express. 7 (6), 2400-2406 (2016).
  41. Mohan, P., Rapoport, N. Doxorubicin as a Molecular Nanotheranostic Agent: Effect of Doxorubicin Encapsulation in Micelles or Nanoemulsions on the Ultrasound-Mediated Intracellular Delivery and Nuclear Trafficking. Mol Pharm. 7 (6), 1959-1973 (2010).
  42. Cielecka-Piontek, J., Jelińska, A., Zając, M., Sobczak, M., Bartold, A., Oszczapowicz, I. A Comparison of the Stability of Doxorubicin and Daunorubicin in Solid State. J. Pharm. Biomed Anal. 50 (4), 576-579 (2009).
  43. Gilbert, C. M., McGeary, R. P., Filippich, L. J., Norris, R. L. G., Charles, B. G. Simultaneous Liquid Chromatographic Determination of Doxorubicin and Its Major Metabolite Doxorubicinol in Parrot Plasma. J. chromatogr. B Analyt. Technol. Biomed. Life sci. 826 (1-2), 273-276 (2005).
  44. Liu, Z. S., Li, Y. M., Jiang, S. X., Chen, L. R. Direct Injection Analysis of Mitomycin C in Biological Fluids by Multidemension High Performance Liquid Chromatography with a Micellar Mobile Phase. J. Liq. Chromatogr. Relat. Technol. 19 (8), 1255-1265 (1996).
  45. Zhou, Y., He, C., Chen, K., Ni, J., Cai, Y., Guo, X., Wu, X. Y. A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside Dialysis Devices Via Numerical Deconvolution. J. Control. Release. 243, 11-20 (2016).

Tags

Keywords: DoxorubicinMitomycin CDoxorubicinolNanoparticlesTumorHPLCSimultaneous QuantitationSample PreparationExtractionInternal Standard
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Zhang, R. X., Zhang, T., Chen, K., Cheng, J., Lai, P., Rauth, A. M., Pang, K. S., Wu, X. Y. Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice. J. Vis. Exp. (128), e56159, doi:10.3791/56159 (2017).
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