Conte, Claudia (2013) CORE-SHELL SUSTAINED RELEASE NANOSYSTEMS FOR THE INTRAVENOUS DELIVERY OF ANTICANCER DRUGS. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: CORE-SHELL SUSTAINED RELEASE NANOSYSTEMS FOR THE INTRAVENOUS DELIVERY OF ANTICANCER DRUGS
Creators:
CreatorsEmail
Conte, Claudiaclaudia.conte@unina.it
Date: 2 April 2013
Number of Pages: 231
Institution: Università degli Studi di Napoli Federico II
Department: Farmacia
Scuola di dottorato: Scienze farmaceutiche
Dottorato: Scienza del farmaco
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
nomeemail
D'Auria, Maria Valeriamadauria@unina.it
Tutor:
nomeemail
Quaglia, Fabianaquaglia@unina.it
Date: 2 April 2013
Number of Pages: 231
Uncontrolled Keywords: nanoparticles, anticancer drugs
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/09 - Farmaceutico tecnologico applicativo
Date Deposited: 09 Apr 2013 11:54
Last Modified: 05 Dec 2014 11:51
URI: http://www.fedoa.unina.it/id/eprint/9407
DOI: 10.6092/UNINA/FEDOA/9407

Abstract

In the last few years, an increased interest is being focused on the development of sustained release nanocarriers pointing to their possible application as intravenous nanomedicines with better performance and lower toxicity as compared to free drugs. We designed and tested several core-shell nanocapsules and nanoparticles (NPs), for the intravenous delivery of both hydrophilic and lipophilic drugs respectively. As base materials, we employed biodegradable amphiphilic block copolymers of poly(-caprolactone) (PCL) and poly(ethyleneoxide) (PEO) with different architectures. In the first stage of the project, stealth aqueous core nanocapsules for the delivery of hydrophilic molecules were prepared by the novel Emulsion/Melting-Sonication technique. Nanocapsules showed optimized technological properties (size, polidispersity index, zeta potential, entrapment efficiency and release rate) and an encouraging cytotoxicity profile, thus representing a nanosystem of great potential in several drug delivery applications, especially for passive targeting of hydrophiphilic drugs to solid tumors. In the second part of the work, core-shell PEO-PCL NPs for the sustained delivery of the highly lipophilic anticancer drug docetaxel (DTX) were obtained by the Melting-Sonication method. NPs were able to entrap high amounts of DTX related to copolymer properties, thus sustaining its release along time and not toxicity toward red blood cells was evidenced. A stronger efficiency in inhibiting cell growth of breast and prostate cancer cells than the free drug and not toxicity in experimental animal models were highlighted. As a final step, we combined DTX with zinc-phtalocyanine (ZnPc), a second generation photosensitizer used in Photodynamic Therapy (PDT), with the aim to obtain a combined chemio/photodynamic nanomedicine. Combined NPs provided high DTX and ZnPc loadings, a slow release of the chemotherapeutic drug and high efficacy of the photosensitizing agent in the singlet oxygen generation. Their high stability in biological environments and the encouraging results obtained by the in vitro data on HeLa cells and by in vivo data on an orthotopic mouse model of amelanotic melanoma, suggested the possibility to employ this system as a translational injactable nanomedicine for the synergistic combination of chemotherapy and PDT.

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