The Sustained-Release Drug Delivery Based on Nano Calcium Carbonate

作者: 韩华锋 * , 孔祥东 :浙江理工大学生命科学学院,杭州; 徐 阳 :浙江理工大学启新学院,杭州;

关键词: 纳米碳酸钙运输载体载药纳米颗粒药物缓释体系Nano-Calcium Carbonate Delivery Carrier Drug-Loading Nanoparticles Drug Delivery System


Objective: The review is to summarize the different preparation methods of nano calcium carbonate as well as the comparison of the advantages and disadvantages of the methods and the characteristics of drug control-released carrier system based on nanometer calcium carbonate, and then to discuss its prospect in the field of biomedical application as the drug carrier. Method: The typical national and international literatures looked up in recent years were analyzed, sorted and concluded. Results and Conclusions: The multifunctional nano calcium carbonate particles have demonstrated the potential as drug control-released carriers or gene carriers. However, they should be further studied with their powerful characteristics.

文章引用: 韩华锋 , 徐 阳 , 孔祥东 (2013) 基于纳米碳酸钙的药物缓释载体研究。 纳米技术, 3, 41-46. doi: 10.12677/NAT.2013.34006


[1] Gutowska, A., Bae, Y.H., Jacobs, H., Feijen, J. and Kim, S.W. (1994) Thermosensitive interpenetrating polymer networks: Synthesis, characterization, and macromolecular release. Macromolecules, 27, 4167-4175.

[2] Felt, O., Buri, P. and Gurny, R. (1998) Chitosan: A unique polysaccharide for drug delivery. Drug Development and Industrial Pharmacy, 24, 979-993.

[3] Uekama, K., Hirayama, F. and Irie, T. (1998) Cyclodextrin drug carrier systems. Chemical Reviews, 98, 2045-2076.

[4] Hofmann, S., Wong Po Foo, C.T., Rossetti, F., Textor, M., Vunjak-Novakovic, G., Kaplan, D., Merkle, H. and Meinel, L. (2006) Silk fibroin as an organic polymer for controlled drug delivery. Journal of Controlled Release, 111, 219-227.

[5] Friess, W. (1998) Collagen-biomaterial for drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 45, 113- 136.

[6] Elvira, C., Mano, J., San Roman, J. and Reis, R. (2002) Starch- based biodegradable hydrogels with potential biomedical applications as drug delivery systems. Biomaterials, 23, 1955-1966.

[7] Kim, S.Y., Shin, I.G. and Lee, Y.M. (1998) Preparation and characterization of biodegradable nanospheres composed of me- thoxy poly (ethylene glycol) and dl-lactide block copolymer as novel drug carriers. Journal of Controlled Release, 56, 197-208.

[8] Riley, T., Stolnik, S., Heald, C., Xiong, C., Garnett, M., Illum, L., Davis, S., Purkiss, S., Barlow, R. and Gellert, P. (2001) Physicochemical evaluation of nanoparticles assembled from poly (lactic acid)-poly (ethylene glycol)(pla-peg) block copolymers as drug delivery vehicles. Langmuir, 17, 3168-3174.

[9] Pitt, C.G., Marks, T. and Schindler, A. (1980) Biodegradable drug delivery systems based on aliphatic polyesters: Application to contraceptives and narcotic antagonists. Academic Press, New York,

[10] Pitt, C.G., Gratzl, M.M., Jeffcoat, A.R., Zweidinger, R. and Schindler, A. (1979) Sustained drug delivery systems II: Factors affecting release rates from poly (ε-caprolactone) and related biodegradable polyesters. Journal of Pharmaceutical Sciences, 68, 1534-1538.

[11] Niwa, T., Takeuchi, H., Hino, T., Nohara, M. and Kawashima, Y. (1995) Biodegradable submicron carriers for peptide drugs: Preparation of dl-lactide/glycolide copolymer (plga) nanospheres with nafarelin acetate by a novel emulsion-phase separation method in an oil system. International Journal of Pharmaceutics, 121, 45-54.

[12] Govender, T., Stolnik, S., Garnett, M.C., Illum, L. and Davis, S.S. (1999) Plga nanoparticles prepared by nanoprecipitation: Drug loading and release studies of a water soluble drug. Journal of Controlled Release, 57, 171-185.

[13] Malam, Y., Loizidou, M. and Seifalian, A.M. (2009) Liposomes and nanoparticles: Nanosized vehicles for drug delivery in cancer. Trends in Pharmacological Sciences, 30, 592-599.

[14] Almeida, A.J. and Souto, E. (2007) Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Advanced Drug Delivery Reviews, 59, 478-490.

[15] Wei, W., Ma, G.-H., Hu, G., Yu, D., Mcleish, T., Su, Z.-G. and Shen, Z-Y. (2008) Preparation of hierarchical hollow CaCo3 particles and the application as anticancer drug carrier. Journal of the American Chemical Society, 130, 15808-15810.

[16] Kong, X.D., Xu, S.J., Wang, X.M., Cui, F.Z. and Yao, J.M. (2012) Calcium carbonate microparticles used as a gene vector for delivering p53 gene into cancer cells. Journal of Biomedical Materials Research Part A, 100A, 2312-2318.

[17] Chowdhury, E.H., Maruyama, A., Kano, A., Nagaoka, M., Kotaka, M., Hirose, S., Kunou, M. and Akaike, T. (2006) Ph- sensing nano-crystals of carbonate apatite: Effects on intracellular delivery and release of DNA for efficient expression into mammalian cells. Gene, 376, 87-94.

[18] Roy, I., Mitra, S., Maitra, A. and Mozumdar, S. (2003) Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery. International Journal of Pharmaceutics, 250, 25- 33.

[19] Uskoković, V. and Uskoković, D.P. (2011) Nanosized hydroxya- patite and other calcium phosphates: Chemistry of formation and application as drug and gene delivery agents. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 96B, 152-191.

[20] Li, Z.-Z., Wen, L.-X., Shao, L. and Chen, J.-F. (2004) Fabrication of porous hollow silica nanoparticles and their applications in drug release control. Journal of Controlled Release, 98, 245- 254.

[21] Bianco, A., Kostarelos, K. and Prato, M. (2005) Applications of carbon nanotubes in drug delivery. Current Opinion in Chemical Biology, 9, 674-679.

[22] Farokhzad, O.C. and Langer, R. (2009) Impact of nanotechnology on drug delivery. ACS Nano, 3, 16-20.

[23] Zhang, Y. (2012) Biocompatibility of porous spherical calcium carbonate microparticles on hela cells. World Journal of Nano Science and Engineering, 2, 25-31.

[24] Schmidt, S. and Volodkin, D. (2013) Microparticulate biomolecules by mild caco3 templating. Journal of Materials Chemistry B, 1, 1210-1218.

[25] Volodkin, D.V., Petrov, A.I., Prevot, M. and Sukhorukov, G.B. (2004) Matrix polyelectrolyte microcapsules: New system for macromolecule encapsulation. Langmuir, 20, 3398-3406.

[26] 王斌, 马祥梅 (2007) 复分解法制备纳米碳酸钙的研究. 新技术新工艺, 4, 64-65.

[27] Yu, J., Lei, M. and Cheng, B. (2004) Facile preparation of monodispersed calcium carbonate spherical particles via a simple precipitation reaction. Materials Chemistry and Physics, 88, 1-4.

[28] 马祥梅, 王斌 (2002) 碳化法制备纳米碳酸钙的研究. 建筑材料学报, 5, 326-329.

[29] 徐惠, 常成功, 刘小育, 范宗良 (2010) 一种针状纳米碳酸钙的制备方法. 无机盐工业, 1, 17-19.

[30] 徐旺生, 何秉忠, 金士威, 宣爱国 (2001) 多级喷雾碳化法制备纳米碳酸钙工艺研究. 无机材料学报, 16, 985-988.

[31] 高明, 吴元欣, 李定或 (2003) 超重力法制备纳米碳酸钙的工艺研究. 化学与生物工程, 6, 19-21.

[32] 李珍, 李正浩 (2002) 微乳液法合成多孔纳米碳酸钙实验研究. 中国粉体技术, 8, 34-36.

[33] Walsh, D., Lebeau, B. and Mann, S. (1999) Morphosynthesis of calcium carbonate (vaterite) microsponges. Advanced Materials, 11, 324-328.

[34] 吉欣, 郭新勇, 武国宝, 仓向辉 (2002) 乳状液膜法制备超细碳酸钙. 化学研究, 13, 44-46.

[35] 陈志军, 张秋云, 坝德伟, 马培华 (2010) 纳米碳酸钙的研究进展. 广州化工, 38, 20-22.

[36] 谢元彦, 杨海林, 阮建明, 周忠诚 (2009) 溶胶–凝胶法制备碳酸钙晶须. 粉末冶金材料科学与工程, 6, 3.

[37] Sukhorukov, G.B., Volodkin, D.V., Günther, A.M., Petrov, A.I., Shenoy, D.B. and Möhwald, H. (2004) Porous calcium carbonate microparticles as templates for encapsulation of bioactive compounds. Journal of Materials Chemistry, 14, 2073-2081.

[38] Volodkin, D.V., Larionova, N.I. and Sukhorukov, G.B. (2004) Protein encapsulation via porous caco3 microparticles templating. Biomacromolecules, 5, 1962-1972.

[39] Li, L., Zhu, Y.-J., Cao, S.-W. and Ma, M.-Y. (2009) Preparation and drug release properties of nanostructured caco3 porous hollow microspheres. Journal of Inorganic Materials, 24, 166-170.

[40] Wang, C., He, C., Tong, Z., Liu, X., Ren, B. and Zeng, F. (2006) Combination of adsorption by porous caco3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery. International Journal of Pharmaceutics, 308, 160-167.

[41] Qiu, N., Yin, H.B., Ji, B.Z., Klauke, N., Glidle, A., Zhang, Y.K., Song, H., Cai, L.L., Ma, L., Wang, G.C., Chen, L.J. and Wang, W.W. (2012) Calcium carbonate microspheres as carriers for the anticancer drug camptothecin. Materials Science and Engineering: C, 32, 2634-2640.

[42] 刘新荣, 黄先洲, 陈学宏, 刘睿颖 (2011) 肝素/碳酸钙微囊的制备及其药物缓释性能. 材料导报, 25, 29-31.

[43] Ueno, Y., Futagawa, H., Takagi, Y., Ueno, A. and Mizushima, Y. (2005) Drug-incorporating calcium carbonate nanoparticles for a new delivery system. Journal of Controlled Release, 103, 93-98.

[44] Wang, J., Chen, J.S., Zong, J.Y., Zhao, D., Li, F., Zhuo, R.X. and Cheng, S.X. (2010) Calcium carbonate/carboxymethyl chitosan hybrid microspheres and nanospheres for drug delivery. The Journal of Physical Chemistry C, 114, 18940-18945,

[45] Peng, C.Y., Zhao, Q.H. and Gao, C.Y. (2010) Sustained delivery of doxorubicin by porous caco3 and chitosan/alginate multilayers-coated CaCo3 microparticles. Colloid Surface A, 353, 132- 139.

[46] Zhao, D., Zhuo, R.-X. and Cheng, S.-X. (2012) Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery. Molecular BioSystems, 8, 753-759.

[47] Tang, J., Sun, D.-M., Qian, W.-Y., Zhu, R.-R., Sun, X.-Y., Wang, W.-R., Li, K. and Wang, S.-L. (2012) One-step bulk preparation of calcium carbonate nanotubes and its application in anticancer drug delivery. Biological Trace Element Research, 147, 408-417.

[48] Cho, K., Wang, X., Nie, S., Chen, Z. and Shin, D.M. (2008) Therapeutic nanoparticles for drug delivery in cancer. Clinical Cancer Research, 14, 1310-1316.

[49] Sung, J.C., Pulliam, B.L. and Edwards, D.A. (2007) Nanoparticles for drug delivery to the lungs. Trends in Biotechnology, 25, 563- 570.

[50] Boado, R.J. (2007) Blood-brain barrier transport of non-viral gene and RNAi therapeutics. Pharmaceutical Research, 24, 1772-1787.

[51] Portney, N.G. and Ozkan, M. (2006) Nano-oncology: Drug delivery, imaging, and sensing. Analytical and Bioanalytical Chemistry, 384, 620-630.

[52] Cheang, T.-Y., Wang, S.-M., Hu, Z.-J., Xing, Z.-H., Chang, G.- Q., Yao, C., Liu, Y., Zhang, H. and Xu, A.-W. (2010) Calcium carbonate/caip6 nanocomposite particles as gene delivery vehicles for human vascular smooth muscle cells. Journal of Materials Chemistry, 20, 8050-8055.

[53] Chen, S., Li, F., Zhuo, R.-X. and Cheng, S.-X. (2011) Efficient non-viral gene delivery mediated by nanostructured calcium carbonate in solution-based transfection and solid-phase transfection. Molecular BioSystems, 7, 2841-2847.

[54] Chen, S., Zhao, D., Li, F., Zhuo, R.X. and Cheng, S.X. (2012) Co-delivery of genes and drugs with nanostructured calcium carbonate for cancer therapy. RSC Advances, 2, 1820-1826.