Simultaneous loading of 5-florouracil and SPIONs in HSA nanoparticles: Optimization of preparation, characterization and in vitro drug release study

Document Type : Research Paper

Authors

1 Protein Research Center, Shahaid Behashti University, Tehran, Iran

2 Biotechnology Group, Chemical Engineering Faculty, Tarbiat Modares University, Tehran, Iran

Abstract

Objective(s): Over the past two decades, considerable interest has been focused on utilizing biocompatible magnetic nanoparticles (MNPs) for biomedical applications. In this study, production of human serum albumin (HSA) nanoparticles using desolvation technique that were simultaneous loaded with high amounts of superparamagnetic iron oxide nanoparticles (SPIONs) and 5-flourouracil (5-FU) was investigated.
Materials and Methods: 5-FU loading (%) and SPIONs entrapment efficiency (%) were optimized using response surface methodology (RSM). The design expert software used to analyse the interactive effects of pH, 5-FU and SPIONs concentrations.
Results:The optimum conditions found to be pH of 8.2, drug concentration of 1.5 mg/ml and SPIONs concentration of 2.79 mg/ml. Under the mentioned optimum conditions, particles with the size of 111.8 nm, zeta potential of -37.1 mV, 5-FU loading of 15.8% and SPIONs entrapment efficiency of 41.1% were obtained. In vitro cumulative release of 5-FU from the nanoparticles was evaluated in phosphate buffer saline (pH 7.4, 37 °C). Results indicated that 85% of the 5-FU released during 95 h, which revealed a sustained release profile. In addition, Vibrating Sample Magnetometer (VSM) analyses confirmed the superparamagnetic properties of magnetic albumin nanoparticles manufactured under the optimum conditions.
Conclusion: According to the findings,SPIONs and 5-FU loaded HAS  nanoparticles arepromising for use as  novel targeted delivery system due to proper magnetic and drug release behaviours.

Keywords


[1]  Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR    imaging and drug delivery. Adv Drug Delivery Rev. (2008)1252 60: 1252-1265.
[2] Mohammad-Taheri M, Vasheghani-Farahani E,   Hosseinkhani H, Shojaosadati SA, Soleimani M. FAbrication and characterization of a new MRI contrast agent based on a magnetic dextran-spermine nanoparticles. Iran J  Polym Sci  Technol. (2012)21: 239-251.
[3]  Chertok B, Moffat B.A, David A.E. Yu F, Bergemann C, Ross BD, Yang VC. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials. 2008; 29: 487-496.
[4]  Kumar CSSR, Mohammad F. Magnetic nanomaterials for hyperthermia-based therapyand controlled drug delivery. Adv. Drug Delivery Rev. 2011; 63: 789-808.
[5]  Laurant S, Dutz S, Hafeli U.O, Mahmoudi M. Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Adv Colloid Interface Sci. 2011; 166: 8-23.
[6]  Pouponeau P, Leroux JC, Soulez G, Gaboury L, Martel S. Co-encapsulationof magnetic nanoparticles and doxorubicin into biodegradable microcarriers for deep tissue targeting by vascular MRI navigation. Biomaterials.  2011; 32: 3481-3486.
[7]  Kratz F. Albumin as a drug carrier: Design of prodrugs, drug conjugates and nanoparticles. J. Controlled Release. 2007; 132: 171-183.
[8]  Wacker M, Zensi A, Kufleitner J, Ruff A, Schütz J, Stockburger T, Marstaller T, Vogel V. A toolbox for the upscaling of ethanolic human serum albumin (HSA) desolvation. Int. J. Pharm., 2011; 46: 225-232.
[9]  Longley DB, Harkin DP, Johnston P.G. 5-Fluorouracil:    mechanisms of action and clinical strategies. Nat. Rev. Cancer, 2003; 3: 330-338.
[10] Pinedo HM, Peters GF. Fluorouracil: biochemistry and pharmacology J Clin Oncol. 1988; 6: 1653-1664.
[11] Alter P, Herzum M, Soufi M, Schaefer JR, Maisch B.    Cardiotoxicity of 5- fluorouracil. cardiovasc Hematol Agents Med Chem. 2006; 4(1): 1-5.
[12] Wigmore PM, Mustafa S, El-Beltagy M, Lyons L, Umka J, Bennett G. Effects of 5-FU. Adv Exp Med Biol. 2010; 678: 157-164.
[13] Fadeian G, Shojaosadati SA, Kouchakzadeh H, Shokri F, Soleimani M. Targeted Delivery of 5-fluorouracil with Monoclonal Antibody Modified Bovine Serum Albumin Nanoparticles. Iranian J Pharm Res. 2015; 14(2) 395-405.
[14] Kouchakzadeh H, Shojaosadati SA, Mohammadnejad J, Paknejad M, Rasaee MJ. Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles for active targeting of breast cancer cells. Hum  Antibodies. 2012; 21: 49-56.
[15] Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 2010; 148(2): 135-146.
[16] Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D. Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm. 2003; 257 (1-2): 169-180.
[17] Pouponeau P, Leroux JC, Martel S. Magnetic nanoparticles encapsulated into biodegradable microparticles steered with an upgraded magnetic resonance imaging system for tumor chemoembolization. Biomaterials. 2009;  30: 6327-6332.
[18] Kouchakzadeh H, Shojaosadati SA, Shokri F. Efficient loading and entrapment of tamoxifen inhuman serum albumin based nanoparticulate delivery system by a modified desolvationtechnique. chem eng res des. 2014; 92: 1681-1692.
[19] Maghsoudi A, Shojaosadati SA, Vasheghani-Farahani E. 5-Fluorouracil-Loaded BSA Nanoparticles: Formulation Optimization and In Vitro Release Study. AAPS PharmSciTech. 2008; 9: 1092-1096.
[20]  Anhorn MG, Mahler HC, Langer K. Freeze drying of human serum albumin (HSA) nanoparticles with different excipients. Int. J. Pharm. 2008; 363: 162-169.
[21] Kouchakzadeh H, Shojaosadati SA, Maghsoudi A, Vasheghani Farahani E. Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology. AAPS PharmSciTech. 2010; 11: 1206-1211.
[22] Calatayud MP, Sanz B, Raffa V, Riggio C, Ibarra MR, Goya GF. The effect of surface charge of functionalized Fe3O4 nanoparticles on protein adsorption and cell uptake. Biomaterials. 2014; 35: 6389-6399.
[23] Issa B, Obaidat IB, Albiss BA, Haik Y. Magnetic Nanoparticles: Surface Effects and Properties Related to Biomedicine Applications. Int J Mol Sci. 2013; 14: 21266–21305.