Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/61464
Title: Hyaluronic acid-coated gold nanoparticles as an anticancer drug delivery system - Biological characterization and efficacy
Author: Parkkola, Hanna
Director: Sendra Cuadal, Judith
Calpena Campmany, Ana Cristina
Keywords: Nanomedicina
Oncologia
Sistemes d'alliberament de medicaments
Nanopartícules
Or
Nanomedicine
Oncology
Drug delivery systems
Nanoparticles
Gold
Issue Date: 1-Dec-2014
Publisher: Universitat de Barcelona
Abstract: [cat] Els actuals tractaments oncòlogics presentan una eficàcia limitada que forcen la recerca de noves teràpies mes eficients. En aquest sentit, la nanotecnologia ha generat moltes expectatives. Durant aquesta tesi, hem desenvolupat un sistema d’alliberaciò de fârmacs formats per nanopartícules d’or (AuNP) recobertes amb àcid hialurònic (HA), dirigit a CD44, una glicoproteïna que es sobreexpresa a la superfície cel.lular de diferents tipus de tumor. Aquest sistema (EDS: Endor Delivery System) proporciona una plataforma per a la conjugaciò de diferents fârmacs antitumorals per tal de tractar el câncer d’una manera més eficient. Aquesta tesi demostra que les propietats úniques que aporten les AuNP es mantenen quan la molqcula que dirigeix al tumor (HA) i l’agent antitumoral sòn conjugats. El recobriment d’HA estabilitza les AuNP, millorant la seva biocompatibilitat. A mps, tambp es demostra que l’EDS va dirigit a CD44, al qual s’uneix i ps internalitzat a les cèl.lules. El nanotransportador no presenta efectes tòxics ni in vitro ni in vivo. Quan el nanotransportador s’uneix a un agent antitumoral (Cisplatí, CIS), es va alliberant de manera gradual en medis fisiològics, a travps de l’acciò de les hialuronidases i del canvi de pH, alliberant el fârmac amb la seva forma activa. L’eficâcia in vivo del CIS conjugat a l’EDS ha mostrat ser superior a la del fârmac lliure. No obstant aixó, sòn necessaris més estudis de seguretat y toxicitat. Nous fàrmacs antitumorals estan sent estudiats per tal de validar l’EDS com una plataforma per a l’alliberaciò de fârmacs antitumorals.
[eng] Novel stategies are needed to improve the limited efficacy of current cancer therapies. High expectations are directed towards nanotechnology-based applications in cancer medicine. We have developed a drug delivery system based on hyaluronic acid (HA) ­coated gold nanoparticles (AuNPs) that targets CD44, a cell surface glycoprotein overexpressed by various cancer cells. This nanocarrier (EDS: Endor Drug Delivery System) provides a platform for the conjugation of anticancer agents for a more efficient cancer treatment. We show that the unique characteristics of AuNPs remain unchanged when the targeting ligand and a chemotherapeutic agent are conjugated. HA-coating stabilizes AuNPs and improves their biocompatibility. EDS is shown to target CD44 and is internalized through this receptor. The nanocarrier does not cause toxic effects in vitro or in vivo. After conjugating an anticancer agent (CIS: cisplatin) to the nanocarrier, EDS shows gradual drug release in physiological media due to changes in pH and hyaluronidase activity, and the drug reaches its target cells in its active form. In vivo efficacy of EDS­CIS conjugate is higher than that of free cisplatin. However, more safety and toxicological studies must be conducted. New drug candidates are being tested in order to validate EDS as a platform for antitumoral drugs.
URI: http://hdl.handle.net/2445/61464
Appears in Collections:Tesis Doctorals - Departament - Farmàcia i Tecnologia Farmacèutica

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