Synthesis and characterization of tamoxifen -loaded magnetic nanoparticles composed of poly ethylene glycol and folic acid

Abstract

Introduction In recent years, magnetic nanoparticles (MNPs) have been evaluated as drug carries for a variety of chemotherapeutic agents, to enhance the efficacy of these drugs.In this thesis Fe3o4 nanoparticles were synthesized from Fe (acac) 3 by a reaction named Thermal decomposition of Fe (acac) 3.MNPs have a significant tendency to agglomerate as a result of their high surface energy, so upon intravenous injection their surfaces are subjected to adsorption of plasma protein or opsonization. Polymeric coatings provide a steric barrier to prevent nanoparticle agglomeration and avoid opsonization. a variety of natural and synthetic polymers have been evaluated for use as coatings on MNPs, such as PEG which is a widely used polymer for nanoparticle coating in biomedical applications, it has different active sites, one site is added to NPs with use of 2- Dopamine hydro bromide, (which has the OH group) and the other side will be change to amine groups, which connect to folic acid, which is widely spread in malignant cells. Folic acid and its analogues displays extremely high affinity for folate receptor on the cell surface, since the FR is over expressed on certain malignant cell types and is present only at low levels in most normal tissues.Materials and methods MNPs (30-40 nm on average) were prepared by thermal decomposition method of Fe (acac) 3 in presence of oleylamine.PEG was added to MNPs with, using amine group of dopamine. N-tert-Butoxycarbonyl-1, 2- ethylendiamine was also use to protect amine group and provide a amine site for binding to folic acid.Fe3o4 NPs were bind through the link of O group of dopamine to Fe, Tamoxifen was loaded physically in the surface of through the synthesis of amine salt, And drug loading test were applied, using buffer phosphate to conduct in vivo condition.Result SEM photomicrographs showed that magnetic nanoparticle were almost spherical in shape, with rather monomodal distribution in size. HNMR and FT-IR was performed for MNPs characterization. All the MNPs were found to have the mean diameter within range of 30-40 nm. FT-IR showed that the drug Tamoxifen was loaded physically on the MNPS surface. SEM images have shown the size of MNPs with tamoxifen between30 and 40 nm.Conclusion The present study deals with tamoxifen which is the most widely used drug for the treatment of estrogen receptor-positive breast cancer, however it also has estrogenic effects on uterus and it`s most significant side effect is to increased risk of endometrial and liver cancer and pulmonary emboli.These side effects were reported to be dose and concentration dependant and can be minimized by reduce the drug concentration in non-target organs and tissues at below levels by this method. MNPs developed on this study may serves as a potential device for delivery of chemotheraupic drugs to malignant cells. As in this thesis Tamoxifen was loaded to MNPs and encapsulation efficacy was about 37 %. We desired that in this ways the side effects would be reduced or vanished. Although hat could be confirmed using cell culture assay and invitro studies.