title: Evaluation of host-guest system to enhance the tamoxifen efficiency.
abstract: Hydrophobic drugs can absorb as guest molecules inside the cavity of cyclodextrins as host sites. So, forming the drug-cyclodextrin complex can exert a profound effect on the physicochemical and biological properties of the drugs. According to these advantages, in this study, we synthesized the tamoxifen (TMX) loaded cyclodextrin (CD)-conjugated MNPs to evaluate simultaneously the cytotoxicity and sustained release as well as hepatoprotective effect of this nanomedicine. The average size of Fe3O4-DPA-PEG-CD-TMX NPs was approximately 31 nm. By energy-dispersive X-ray spectroscopy (EDS), it was revealed that Fe3O4constitutes 14.34% of the composition of modified MNPs. In the other words, nearly 85% of Fe3O4-DPA-PEG-CD NPs are made of dopamine (DPA), polyethylene glycol (PEG) and β-cyclodextrin (β-CD). The TMX loaded MNPs (with entrapment efficiency of 33 mg TMX per unit CD (mg) and loading efficiency of 87.5%) showed sustained liberation of TMX molecules (with 91% release in 120 h). Cytotoxicity assay and apoptosis assay by TUNEL analysis revealed that the engineered Fe3O4-DPA-PEG-CD-TMX NPs were able to significantly inhibit the MCF-7 breast cancer cells. According to effect of CD on TMX sustained release, it was found that CD can decrease the hepatotoxicity induced by TMX nearly 30%. Based upon these findings, we suggest the Fe3O4-DPA-PEG-CD-TMX NPs as an effective multifunctional nanomedicine with simultaneous therapeutic and hepatoprotective effects.
authors.affiliation: a Faculty of Pharmacy , Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Heidari Majd
authors.affiliation: b Stem Cell Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbarzadeh
authors.affiliation: a Faculty of Pharmacy , Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Sargazi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D061251:Primary Cell Culture; D051381:Rats; D013629:Tamoxifen / Q000737:chemistry / Q000494:pharmacology*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D047392:beta-Cyclodextrins; D013629:Tamoxifen; D011092:Polyethylene Glycols; D004298:Dopamine; D052203:Ferrosoferric Oxide
keywords: Cyclodextrin; drug delivery; magnetic nanoparticles; tamoxifen