Volume 22, Issue 3 (2019)                   mjms 2019, 22(3): 113-120 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Nejati S, Imani R, Sharifi A. Synthesis and Characterization of Two Sustained Release Systems of Micro- and Nano-sized Particles for Controlled Release of Atorvastatin for Bone Tissue Engineering Applications. mjms 2019; 22 (3) :113-120
URL: http://mjms.modares.ac.ir/article-30-20850-en.html
1- Biomaterial Department, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran, Iran
2- Amirkabir University of Technology, NO 350, Hafex Street, Valiasr Square, Tehran, Iran , r.imani@aut.ac.ir
3- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
Abstract:   (6671 Views)
Aims: Using osteoinductive agents in combination with tissue engineering scaffolds is considered as a new approach to bone repair. Recently, statins have attracted great attention among a variety of drugs used in bone repair. In order to achieve a sustained release of Atorvastatin from bone scaffolds, two systems, including nanoniosomes and gelatin microspheres, were synthesized and compared.
Materials and Methods: Nanoniosomes and gelatin microspheres were prepared by thin-film hydration and single emulsion technique, respectively.
Findings: The prepared systems were characterized for morphology, size, carriers’ preparation efficiency, encapsulation efficiency, and drug loading. Also, release profiles of them were evaluated over a period of one week. The results indicated the formation of relatively spherical niosomes with the diameter of about 653.52nm and encapsulation efficiency of 81.34%, and formation of gelatin microspheres with the diameter of about 37.5μm and the encapsulation efficiency of 78.93%.
Conclusion: The results showed that gelatin microspheres had a lower burst release than niosomes, and niosomes had more sustained release than gelatin microspheres after 24hr to 1 week. Albeit, selection of the optimal system requires cellular studies and also the selection must occur according to the severity of the damage and the rate of repair.
Full-Text [PDF 1147 kb]   (2557 Downloads)    
Article Type: Original Research | Subject: Tissue Engineering
Received: 2018/05/14 | Accepted: 2019/03/14

1. Wang Y, Zhu G, Li N, Song J, Wang L, Shi X. Small molecules and their controlled release that induce the osteogenic/chondrogenic commitment of stem cells. Biotechnol Adv. 2015;33(8):1626-40. [Link] [DOI:10.1016/j.biotechadv.2015.08.005]
2. Garrett IR, Gutierrez G, Mundy GR. Statins and bone formation. Curr Pharm Des. 2001;7(8):715-36. [Link] [DOI:10.2174/1381612013397762]
3. Balmayor ER. Targeted delivery as key for the success of small osteoinductive molecules. Adv Drug Deliv Rev. 2015;94:13-27. [Link] [DOI:10.1016/j.addr.2015.04.022]
4. Ross Garrett I, Mundy GR. The role of statins as potential targets for bone formation. Arthritis Res. 2002;4(4):237-40. [Link] [DOI:10.1186/ar413]
5. Steinberg D. Hypercholesterolemia and inflammation in atherogenesis: Two sides of the same coin. Mol Nutr Food Res. 2005;49(11):995-8. [Link] [DOI:10.1002/mnfr.200500081]
6. Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006;85(6):520-3. [Link] [DOI:10.1177/154405910608500608]
7. Pullisaar H, Reseland JE, Haugen HJ, Brinchmann JE, Østrup E. Simvastatin coating of TiO₂ scaffold induces osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2014;447(1):139-44. [Link] [DOI:10.1016/j.bbrc.2014.03.133]
8. Ferreira LB, Bradaschia-Correa V, Moreira MM, Marques ND, Arana-Chavez VE. Evaluation of bone repair of critical size defects treated with simvastatin-loaded poly(lactic-co-glycolic acid) microspheres in rat calvaria. J Biomater Appl. 2015;29(7):965-76. [Link] [DOI:10.1177/0885328214550897]
9. Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm. 2009;377(1-2):1-8. [Link] [DOI:10.1016/j.ijpharm.2009.04.020]
10. Zou Y, Brooks JL, Talwalkar V, Milbrandt TA, Puleo DA. Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs. J Biomed Mater Res B Appl Biomater. 2012;100(1):155-62. [Link] [DOI:10.1002/jbm.b.31933]
11. Prajapati KP, Bhandari A. Spectroscopic method for estimation of atorvastatin calcium in tablet dosage form. Indo Glob J Pharm Sci. 2011;1(4):294-9. [Link]
12. Dinarvand R, Mahmoodi S, Farboud E, Salehi M, Atyabi F. Preparation of gelatin microspheres containing lactic acid--effect of cross-linking on drug release. Acta Pharm. 2005;55(1):57-67. [Link]
13. Selcan Gungor-Ozkerim P, Balkan T, Kose GT, Sezai Sarac A, Kok FN. Incorporation of growth factor loaded microspheres into polymeric electrospun nanofibers for tissue engineering applications. J Biomed Mater Res A. 2014;102(6):1897-908. [Link] [DOI:10.1002/jbm.a.34857]
14. Farhangi M, Dadashzadeh S, Bolourchian N. Biodegradable gelatin microspheres as controlled release intraarticular delivery system: The effect of formulation variables. Indian J Pharm Sci. 2017;79(1):105-12. [Link] [DOI:10.4172/pharmaceutical-sciences.1000206]
15. Venkataraman Sh, Hedrick JL, Ong ZY, Yang C, Rachel Ee PL, Hammond PT, et al. The effects of polymeric nanostructure shape on drug delivery. Adv Drug Deliv Rev. 2011;63(14-15):1228-46. [Link] [DOI:10.1016/j.addr.2011.06.016]
16. Uchegbu IF, Schätzlein AG, Cheng WP. Fundamentals of pharmaceutical nanoscience. Springer-Verlag: New York;2013. [Link] [DOI:10.1007/978-1-4614-9164-4]
17. Muzzalupo R, Tavano L, La Mesa C. Alkyl glucopyranoside-based niosomes containing methotrexate for pharmaceutical applications: evaluation of physico-chemical and biological properties. Int J Pharm. 2013;458(1):224-9. [Link] [DOI:10.1016/j.ijpharm.2013.09.011]
18. Varalakshmi PR, Kavitha M, Govindan R, Narasimhan S. Effect of statins with α-tricalcium phosphate on proliferation, differentiation, and mineralization of human dental pulp cells. 2013;39(6):806-12. [Link] [DOI:10.1016/j.joen.2012.12.036]
19. Nyan M, Miyahara T, Noritake K, Hao J, Rodriguez R, Kuroda S, et al. Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate. J Biomed Mater Res B Appl Biomater. 2010;93(1):65-73. [Link] [DOI:10.1002/jbm.b.31559]
20. Qi Y, Zhao T, Yan W, Xu K, Shi Z, Wang J. Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model. Cytotherapy. 2013;15(1):44-56. [Link] [DOI:10.1016/j.jcyt.2012.10.006]
21. Yan Q, Xiao LQ, Tan L, Sun W, Wu T, Chen LW, et al. Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics. J Biomed Mater Res A. 2015;103(11):3580-9. [Link] [DOI:10.1002/jbm.a.35499]
22. Terukina T, Naito Y, Tagami T, Morikawa Y, Henmi Y, Prananingrum W, et al. The effect of the release behavior of simvastatin from different PLGA particles on bone regeneration in vitro and in vivo: Comparison of simvastatin-loaded PLGA microspheres and nanospheres. J Drug Deliv Sci Technol. 2016;33:136-42. [Link] [DOI:10.1016/j.jddst.2016.03.005]
23. Wang H, Liu J, Tao S, Chai G, Wang J, Hu FQ, et al. Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system. Int J Nanomedicine. 2015;10:5671-85. [Link] [DOI:10.2147/IJN.S88798]

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.