New Drug Delivery System for Cancer Therapy
The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O2 medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1089551Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 3205
 M. A. Elhissi, W. Ahmed, A. Israr Ul Hassan, R. Dhanak Vinod., and A. D’Emanuele, "Carbon nanotubes in cancer therapy and drug delivery,” Journal of Drug Delivery, pp. 1-10, 2012.
 Z. Liu, K. Chen, C. Davis, S. Sherlock, Q. Cao, X. Chen, and H. Dai1, "Drug delivery with carbon nanotubes for in vivo cancer treatment,” Cancer Res., vol. 68 (16), pp. 6652–6660, 2008.
 G. Ciofani, V. Raffa, A. Menciassi, and A. Cuschieri, "Folate functionalized boron nitride nanotubes and their selective uptake by glioblastoma multiforme cells: implications for their use as boron carriers in linical boron neutron capture therapy,” Nanoscale Res. Lett., pp.113-121, 2008.
 Q. Yuan, S. Hein, R. D. Misra, "New generation of chitosan-encapsulated ZnO quantum dots loaded with drug: Synthesis, characterization and in vitro drug delivery response,” Acta Biomater, pp. 2732–2739, 2010.
 L. Jingyuan, G. Dadong Xuemei, H. Wang, H. Jiang Wang, B. Chen, "The photodynamic effect of different size zno nanoparticles on cancer cell proliferation in vitro,” Nanoscale Res. Lett., vol 5, pp. 1063-1071, 2010.
 K. Yogendra, K. M. Mahadevan, N. Sunee, N. Madhusudhana. "Photocatalytic activity of synthetic ZnO composite against Coralene red F3BS dye in presence of solar light,” Int. J. Environ. Sci., vol. 1(5), pp. 839-846, 2011.
 K. Ghule, A. Vithal Ghule, B.-J. Chen, and Y.-C. Ling, "Preparation and characterization of ZnO nanoparticles coated paper and its antibacterial activity study,” Green Chem., vol 8, pp. 1034 – 1041, 2006.
 C. Hanley, J. Layne, A. Punnoose, K. M. Reddy, I. Coombs, A. Coombs, K. Feris, and D. Wingett, "Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles,” Nanotechnology, vol. 19, pp.1-10, 2008.
 S. Ostrovsky, G. Kazimirsky, A. Gedanken, and C. Brodie., "Selective cytotoxic effect of ZnO nanoparticles on glioma cells,” Nano Res., vol 2, pp. 882- 890, 2009.
 D. Guo, C. Wu, H. Jiang, Q. Li, X. Wang, and B. Chen, "Synergistic cytotoxic effect of different sized ZnO nanoparticles and daunorubicin against leukemia cancer cells under UV irradiation,” J Photochem. Photobiol. B, vol 93, pp. 119–126, 2008.
 S. Nair, A. Sasidharan, V. V. Divya Rani, D. Menon, S. Nair, K. Manzoor, and S. Raina, "Role of size scale of ZnO nanoparticles and microparticles on toxicity toward bacteria and osteoblast cancer cells,” J Mater Sci Mater Med. vol 20, pp. 235–241, 2009.
 C. Hanley, A. Thurber, C. Hanna, A. Punnoose, J. Zhang, and D. G. Wingett, "The influences of cell type and ZnO nanoparticle size and immune cell cytotoxicity and cytokine induction,” Nanoscale Res Lett. vol 4, pp. 1409–1420, 2009.
 H. Wang, D. Wingett, M.H. Engelhard, K. Feris, K. M. Reddy, P. Turner, J. Layne, C. Hanley, J. Bell, D. Tenne, C. Wang, and A. Punnoose, "Fluorescent dye encapsulated ZnO particles with cellspecific toxicity for potential use in biomedical applications.” J Mater. Sci. Mater. Med., vol 20, pp. 11–22, 2009.
 W. J. Rasmussen, E. Martinez, L. Panagiota, and D. G. Wingett, "Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications,” NIH PA., vol 7(9), pp. 1063-1067, 2010.
 B. Wang, W. Feng, M. Wang, T. Wang, Y. Gu, M. Zhu, H. Ouyang, J. Shi, F. Zhang, Y. Zhao, Z. Chai, H. Wang, and J. Wang, "Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice,” J. Nanopart. Res., vol 10, pp. 263–276, 2008.
 E. Arakelova, V. Parvanyan, F. Grigoryan, G. Asatryan, and G. Petrosyan, "Increase in concentration of a Zn-containing volatile complex by UV irradiation of a target for ZnO films synthesis,” EPD Congress 2006, TMS (The Minerals, Metals & Materials Society), San Antonio, Texas, pp. 813-818, 2006.
 E. Arakelova, F. Grigoryan V. Parvanyan, and G. Asatryan, "Study of decomposition regularities for a Zn-containing volatile complex used in ZnO films synthesis,” EPD Congress 2006, TMS (The Minerals, Metals & Materials Society), San Antonio, Texas, pp. 883-888, 2006.
 V. G. Parvanyan, F. A. Grigoryan, E. R. Arakelova, G. G. Asatryan, G. N. Mirzoyan, and G. G. Petrosyan. "Formation and decomposition regularities of a Zn-containing volatile complex for ZnO films synthesis,” Kinetika i kataliz, v.48, (3), pp. 1-4, 2007.
 E. Arakelova, A. Khachatryan, K. Avjyan, A. Voskanyan, Z. Farmazyan, A. Mirzoyan, T. Jivanshiryan, L. Savshenko, S. Ghazaryan, K. Grigoryan, and F. Arsenyan, "Zinс oxide nanocomposites with antitumor activity,” Nat. Sci., vol 2(2), pp. 1341-1348, 2010.
 S. H. Minasyan, S. H. Ghazaryan, V. S. Tonoyan, S. A. Bajinyan, K. P. Grigoryan, F. T. Greenaway, and J. R. S. Sorensen, "Synthesis, characterization and measurement of antioxidant reactivity of Salicylidene-DLTyrosine ethyl esters and copper(II) Salicylidene-DL-Tyrosine ethyl esters)2 in linoleic acid peroxidation reaction system,” Synth. React. Inorg. Met.-Org. Nano-Metal Chem., vol 36(5), pp. 425-434, 2006.
 E. Arakelova, A. Khachatryan, K. Avjyan, Z. Farmazyan, L. Savshenko, A. Mirzoyan, S. Ghazaryan, and F. Arsenyan, "Method of obtaining anticancer composite films and coatings”. Patent Republic of Armenia, № 2481A, 25.01.2011.
 A. Mirzoyan, E. Arakelova, and Z. Farmazyan, "Antitumor zinc oxide composites of salicyliden amino acids,” Vestnik (Russian), vol 79(2), pp. 492-499, 2012.
 R. T. Hoare and S. D. Kohane. "Hydrogels in drug delivery: Progress and challenges,” Polymer, vol 49, pp.1993-2007, 2008.
 C. Sutton, "Adhesions and their prevention,” The Obstetrician and Gynecologist, vol 7, pp. 168-76, 2005.
 L. Yu, Z. Zhang, H. Zhang, and J. Ding, "Biodegradability and biocompatibility of thermoreversible hydrogels formed from mixing a sol and a precipitate of block copolymers in water,” Biomacromolecules, vol. 11, pp. 2169–78, 2010.
 D. P. Subedi, D. K. Madhup, A. Sharma, U. M. Joshi, and A. Huczko, "Study of the wettability of ZnO nano films,” Int. Nano Lett., vol 1( 2), pp. 117-122, 2011.