Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles

(2017) Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles. Artificial Cells, Nanomedicine and Biotechnology. pp. 1728-1739. ISSN 21691401 (ISSN)

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Abstract

A reliable and efficient drug delivery system using PCL–PEG–PCL copolymers was established for the anti-cancer compound sulforaphane (SF) in this study. Encapsulated SF by PCL–PEG–PCL nanoparticles led to formation of SF-loaded PCL–PEG–PCL micelles. Micelles characterization and stability, the particle size and their morphology were determined by DLS and AFM. The loading efficiency of SF was 19.33 ± 1.28. The results of AFM showed that the micelles had spherical shapes with the size of 107 nm. In vitro release of SF from SF-entrapped micelles was remarkably sustained. The cytotoxicity of free SF, PCL–PEG–PCL and SF/PCL–PEG–PCL micelles was analysis by MTT colorimetric assay on MCF-7, 4T1 and MCF10A cell lines. Expression levels of BCL-2, PARP, COX-2, Caspase-9 and ACTB genes were quantified by real-time PCR. Flow cytometry analysis was performed using the Annexin V-FITC Apoptosis Detection Kit to evaluate the apoptotic effects of free SF compared with SF/PCL–PEG–PCL micelles. Study of the in vivo pharmacokinetics of the SF-loaded micelles was carried out on SF-loaded PCL–PEG–PCL micelles in comparison with free SF. The results of in vivo experiments indicated that the SF loaded micelles significantly reduced the tumor size. In vivo results showed that the multiple injections of SF-loaded micelles could prolong the circulation period and increase the therapeutic efficacy of SF. Also, in comparison with the free-SF solution, encapsulation of the SF in micelles increased the mean residence time from 0.5 to 4 h and the area under the concentration–time curve up to 50 folds. © 2017 Zanjan University of Medical Sciences.

Item Type: Article
Keywords: d,l-Sulforaphane (SF) Drug delivery micelles PCL–PEG–PCL Cell culture Cell death Colorimetric analysis Controlled drug delivery Gene expression Particle size Pharmacokinetics Polyethylene glycols Polyethylene oxides Polymerase chain reaction Targeted drug delivery Colorimetric assays Efficient drug delivery Flow cytometry analysis In-vivo experiments Mean residence time Multiple injections Sulforaphane Therapeutic efficacy beta actin caspase 9 copolymer cyclooxygenase 2 fluorescein isothiocyanate lipocortin 5 nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase polycaprolactone protein bcl 2 drug carrier isothiocyanic acid derivative macrogol derivative nitric oxide poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone) polyester sulforafan 4T1 cell line animal experiment animal model antineoplastic activity apoptosis aqueous solution area under the curve Article atomic force microscopy breast cancer cancer inhibition cell viability colorimetry controlled study cytotoxicity dispersity drug clearance drug delivery system drug half life drug release female flow cytometry gene expression profiling human human cell hydrodynamics hydrophobicity in vitro study in vivo study maximum plasma concentration MCF-10A cell line MCF-7 cell line micelle molecular stability molecular weight mouse MTT assay nanoencapsulation nonhuman pharmacokinetic parameters photon correlation spectroscopy physical chemistry plasma concentration-time curve polymerization protein expression real time polymerase chain reaction single drug dose surface charge surface property survival rate therapy effect time to maximum plasma concentration tumor volume volume of distribution cell line chemistry drug effect hemolysis metabolism tissue distribution Drug Carriers Drug Liberation Humans Isothiocyanates Polyesters
Page Range: pp. 1728-1739
Journal or Publication Title: Artificial Cells, Nanomedicine and Biotechnology
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q2
Volume: 45
Number: 8
Identification Number: https://doi.org/10.1080/21691401.2017.1282501 http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=97&SID=C48LsSa76YoWspN8AAK&page=1&doc=5
ISSN: 21691401 (ISSN)
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/355

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