Hollow microspheres based on - folic acid modified - hydroxypropyl Cellulose and synthetic multi-responsive bio-copolymer for targeted cancer therapy

dc.contributor.author	Μεταξά, Αικατερίνη-Φωτεινή	el
dc.contributor.author	Ευθυμιάδου, Ελένη Κ.	el
dc.contributor.author	Μπούκος, Νίκος Κ.	el
dc.contributor.author	Φραγκογιώργη, Ειρήνη Α.	el
dc.contributor.author	Λούντος, Γεώργιος	el
dc.date.accessioned	2015-06-09T19:06:55Z
dc.date.available	2015-06-09T19:06:55Z
dc.date.issued	2015-06-09
dc.identifier.uri	http://hdl.handle.net/11400/15615
dc.rights	Αναφορά Δημιουργού-Μη Εμπορική Χρήση-Όχι Παράγωγα Έργα 3.0 Ηνωμένες Πολιτείες	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/us/	*
dc.source	http://www.sciencedirect.com/science/article/pii/S0021979714005451	en
dc.subject	Μικροσφαιρίδια
dc.subject	Πολυσακχαρίτες
dc.subject	Νταουνορουμπικίνη
dc.subject	Σύστημα χορήγησης φαρμάκων
dc.subject	Φολικό οξύ
dc.subject	Microspheres
dc.subject	Polysaccharides
dc.subject	daunorubicin
dc.subject	Drug delivery system
dc.subject	Folic acids
dc.title	Hollow microspheres based on - folic acid modified - hydroxypropyl Cellulose and synthetic multi-responsive bio-copolymer for targeted cancer therapy	en
heal.type	journalArticle
heal.secondaryTitle	controlled release of daunorubicin, in vitro and in vivo studies	en
heal.classification	Χημεία
heal.classification	Φαρμακευτική
heal.classification	Chemistry
heal.classification	Pharmacy
heal.classificationURI	N/A-Χημεία
heal.classificationURI	N/A-Φαρμακευτική
heal.classificationURI	http://skos.um.es/unescothes/C00568
heal.classificationURI	http://id.loc.gov/authorities/subjects/sh85100603
heal.keywordURI	http://id.loc.gov/authorities/subjects/sh85084923
heal.keywordURI	http://id.loc.gov/authorities/subjects/sh85104728
heal.keywordURI	http://lod.nal.usda.gov/148792
heal.contributorName	Κόρδας, Γεώργιος	el
heal.identifier.secondary	DOI: 10.1016/j.jcis.2014.08.001
heal.language	en
heal.access	campus
heal.recordProvider	Τεχνολογικό Εκπαιδευτικό Ίδρυμα Αθήνας. Σχολή Τεχνολογικών Εφαρμογών. Τμήμα Μηχανικών Βιοϊατρικής Τεχνολογίας Τ.Ε.	el
heal.publicationDate	2014-09-01
heal.bibliographicCitation	Metaxa, A.F., Efthimiadou, E.K., Boukos, N., Fragogeorgi, E.A., Loudos, G. et al. (2014) Hollow microspheres based on - Folic acid modified - Hydroxypropyl Cellulose and synthetic multi-responsive bio-copolymer for targeted cancer therapy: Controlled release of daunorubicin, in vitro and in vivo studies. Journal of Colloid and Interface Science. [Online] 435, pp.171-181. Available from: http://www.sciencedirect.com [Accessed 09/06/2015]	en
heal.abstract	Hypothesis: Conventional chemotherapy drugs such as anthracyclines show no specific activity. They destroy cancer cells but also and the healthy ones, and for that reason exhibit high toxicity. In order to alleviate the toxic effects of chemotherapeutic drugs, the administration dose is being minimized, while their reactivity against tumor cells is lessened. This problem can be overcome or at least reduced by using nanoscale drug delivery systems to target the pathogenic area. The present work deals with the synthesis, characterization and biological evaluation of multi-responsive hollow microspheres coated with Hydroxypropyl Cellulose (HPC)-a biocompatible and thermosensitive polysaccharide-conjugated with folic acid as well promising drug vehicles for targeted cancer therapy. Experiments: The synthetic route consists of two steps. In the first step, a single layer of sensitive copolymers is ((Methacrylic acid (MAA), N-(2-Hydroxypropyl) methacrylamide (HPMA) and N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(2-methylacrylamide) (DSBMA)) fabricated on a sacrificial template of SiO2 and in the second step, an additional layer of the folic acid modified HPC coat the microspheres' surface. The layers fabrication is performed through a combination of distillation precipitation co-polymerization and chemical deposition method. The loading capacity (% LC) and encapsulation efficiency (% EE) percentages of the chemotherapeutic agent daunorubicin (DNR) in the fabricated microspheres were calculated through the standard curve methodology. In addition, the releasing properties of the resulting spheres are investigated, using the above mentioned methodology. It is worth mentioning that, spheres release the entrapped drug under combined conditions such acidic and reductive environment along with conventional hyperthermia. Cytotoxic activity of the synthesized spheres was investigated by using the well-established method of MTT assay in MCF-7 (breast cancer), HeLa (cervical cancer) and HEK 293 (Human Embryonic Kidney healthy cells) cell lines. Confocal and fluorescence microscopy were used to confirm the in vitro targeted ability of folic acid modified drug loaded microspheres in HeLa, to that overexpress folate receptors, MCF-7 and 3T3 cells, as negative folate cell substrate. Finally, radiolabelling of the spheres is performed, with a gamma emitting radionuclide (99mTc), to assess their in vivo profile by means of scintigraphic imaging and biodistribution studies. Findings: Hollow spheres release the encapsulated drug under acidic environment, conventional hyperthermia or in the presence of glutathione (reductive environment). The ability of modified drug carriers to target the HeLa cells, was confirmed by confocal and fluorescence microscopy. The resulting spheres are observed to be promising drug-carriers for cancer treatment due to their releasing properties under tumor's environment and high concentration in HeLa cells via endocytosis. In addition, the empty vehicles have no toxicity in healthy cells and present antimicrobial activity.	en
heal.publisher	Academic Press Inc.	en
heal.journalName	Journal of Colloid and Interface Science	en
heal.journalType	peer-reviewed
heal.fullTextAvailability	true