Document Type : Full Research Paper


1 M.Sc Student, Biotechnology Group, Payam Noor University, Tehran, Iran

2 Assistant Professor, Food and Agriculture Department, Research Standard Institute, National Standard Organization of Iran, Karaj, Iran

3 Asisitant Professor, Biomedical Engineering Group, Chemical Engineering Department, Tarbiat Modares University, Tehran, Iran

4 Asistant Professor, Biotechnology Group, Engineering Department, Payam Noor University, Tehran, Iran

5 Asistant Professor, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran



The aim of this research is the preparation of a system based on mesoporous silica nanoparticles (MSN) for delivery of Rivastigmine hydrogen tartrate and investigating of the system cytotoxicity, with or without drugs, on the human brain neuroblastoma cells (SY5Y). Rivastigmine is a hydrophilic and a hydrophobic drug which is used for treatment of Alzimerʾs disease. In this study MSN were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, N2 adsorption isotherms, and z-potential analysis.  Results showed that all MSN were spherical with the same structure. The mean size of nanoparticles was 100±13 nm and the mean diameter of pores was 2.15 nm. The loading capacity and efficiency of rivastigmine hydrogen tartrate were obtained 20.88, and 25%, respectively. Release of rivastigmine from nanoparticles in the simulated gastric and body fluid during 24 h were obtained 70.5 and 79.6%, respectively, which was shown the slightly fast release of rivastigmine in simulated gastric fluid. The cytotoxicity effect of nanoparticles with and without rivastigmine was done by MTT assay on SY5Y cell lines.  Results showed that the in vitro rivastigmine release from the nanoparticles containing of it exhibited the more treatment property as free rivastigmine on SY5Y.


Main Subjects

[1]       Site of Alzheimer’s Association:
[2]       D. Sherita McLamore, Exelon® patch (Revastigmine) Transdermal Delivery System, Chem rev NDA: 22-083. Novartis. HFD-120.
[3]       A. L. Chan, Y. W. Chien, S. Jin Lin, “Transdermal delivery of treatment for Alzheimer’s disease: development, clinical performance and future prospects” Drug Aging 25,  761-775, 2008.
[4]       P. Sozio, L. S. Cerasa, L. Marinelli, A. Di Stefano, “Transdermal donepezil on the treatment of Alzheimer’s diseaseNeuropsychiatr Dis Treat 8, 361-8, 2012.
[5]       M. Vallet Regi, A. Rámila, R. P. del Real, J. Pérez Pariente, “A New Property of MCM-41: Drug Delivery SystemChem Mater 13, 308-11, 2001.
[6]       A. Bayu, D. Nandiyanto, S. G. Kim, F. Iskandar, K. Okuyama, “Synthesis of spherical mesoporous silica nanoparticles with nanometer-size controllable pores and outer diametersMicropor Mesopor Mat 120, 447-453, 2009.
[7]       M. Vallet-Regi, F. Balas, D. Arcos, “Mesoporous materials for drug deliveryAngew Chem Int Ed Engl 46, 7548-58, 2007.
[8]       D. Jin, K. W. Park, J. H. Lee, K. Song, “The selective immobilization of curcumin onto the internal surface of mesoporous hollow silica particles by covalent bonding and its controlled release”  J Mater Chem 21, 3641-3645, 2011.
[9]       Y. Zhang, Z.  Zhi, T.  Jiang, J. Zhang, Z. Wang, S. Wang,  “Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan  J Control Release 145, 257-63, 2010.
[10]   I. I. Slowing, B. G. Trewyn, V. S. Y. Lin, “Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells J Amer Chem Soc 128, 14792-3, 2006.
[11]   L. Rashidi, E. Vasheghani-Farahani, K. Rostami, F. Ganji, M. Fallahpour, “Mesoporous silica nanoparticles with different pore sizes for delivery of pH-sensitive gallic acid” Asia-Pac J Chem Eng 9, 845–853, 2014.
[12]   I. I. Slowing, B. G. Trewyn, V. S. Y. Lin, “Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins J Am Chem Soc 129, 8845-8849, 2007.
[13]   M. Fazila, S. Md, S. Haque, M. Kumar, S. Baboota, J. K. Sahni, J. Ali, “Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targetingEur J Pharm Sci, 47, 6-15, 2012.
[14]   K. Arumugam, G. S. Sundararajan, S. R. Mallayasamy, R. K. Averineni, M. S. Reddy, N. Udupa, “A study of rivastigmine liposomes for delivery into the brain through intranasal routeActa Pharm 58, 287-297, 2008.
[15]   A. Vintiloiu, M. Lafleur, G. Bastiat, J. Leroux,”In Situ-Forming Oleogel Implant for Rivastigmine DeliveryPharm Res 25, 845-852, 2008.
[16]   R. Makkar, P. Singh, C.C. Danta, V. Kakkar, I. P.  Kaur, P. Piplani, “Newly Synthesized Acetylcholinesterase Inhibitors for Alleviating Alzheimer’s Disease using Solid Lipid NanoparticlesCurr Drug Therap   9, 111-123, 2014.
[17]   A. M. Avachat, Y. M. Oswal, K. N. Gujar, R. D. Shah, “Preparation and Characterization of Rivastigmine Loaded Human Serum Albumin (HSA) NanoparticlesCur Drug Deliv 11, 359-70, 2014.
[18]   E. F. Craparo, G. Pitarresi, M. L. Bondi, M. P. Casaletto, M. Licciardi, G. Giammona, “A nanoparticulate drug-delivery System for rivastigmine: physico-chemical and in vitro Biological CharacterizationMacromol Biosci 8, 247-59, 2008.
[19]   K. Simar preet, R. Rekha, H. Afzal, K. Sarita,Preparation and Characterization of Rivastigmine Loaded Chitosan NanoparticlesJ Pharm Sci Res  3, 1227-32, 2011.
[20]   S. A. Joshi, S. S. Chavhan, K. K. Sawant, “Rivastigmine-loaded PLGA and PBCA nanoparticles: Preparation, optimization, characterization, in vitro and pharmacodynamic studiesEur J Pharm Biopharm 76, 189-99, 2010.
[21]   K. Pagar, P. Vavia, “Rivastigmine-L-lactide-depsipeptide Polymeric NanoparticlesSci Pharm 81, pp 86585, 2013.
[22]   L. Rashidi, E. Vasheghani-Farahani, M. Soleimani, A. Atashi, K. Rostami, F. Gangi, “A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells” J Nanopart Res 16, 1-9, 2014.
[23]   O. Vijaykumar, V. F. Joe, B. A. Vishwanath, “Formulation and evaluation of rivastigmine loaded polymeric nanoparticles” J Chem Pharm Res 6, pp 556, 2014.
[24]    ل. رشیدی، «تهیه نانوذرات مزومتخلخل سیلیکا برای رهایش پاداکساینده­های طبیعی در سلول­های Caco-2»، پایان­نامه دکترا، دانشگاه تربیت مدرس، 1392.