Breast cancer is the most common malignancy in women worldwide. Therapeutic strategies currently involve a combination of surgery, radiotherapy, immunotherapy, hormone therapy and/or chemotherapy. The efficacy of a chemotherapeutic formulation depends on its ability to selectively target diseased tissue, overcome biological barriers, and intelligently respond to the disease environment to release cytotoxic agents. The development of a controlled and targeted drug delivery system may result in a more efficient and less harmful solution to overcome the limitations associated with conventional chemotherapy (Cho et al.). Recent studies have been focused on developing nanoscale delivery vehicles capable of controlling the release of chemotherapeutics directly inside cancer cells. Micellar like nanoparticles (NPs) are produced by the self-assembly of amphiphilic molecules into a structure with a hydrophobic core and an hydrophilic outer layer, with diameters generally less than 100 nm, allowing them to extravasate through the tumor vessels fenestrations. Moreover, their hydrophilic surfaces may shield them from immediate recognition by reticuloendothelial system (RES) leading to an increase in their circulation time. Many micellar formulations are currently under clinical evaluation for the treatment of cancer (e.g. doxorubicin, paclitaxel and epirubicin). Therefore, the aim of this study was to synthesize a series of linear-block and star-shaped copolymers based on polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL), and to formulate noscapine (NOS) loaded biodegradable NPs by the nanoprecipitation technique. After characterization of these NPs, the best formulae were tested for in-vitro release and cytotoxicity using MCF-7 breast cancer cells. Pharmacokinetic parameters and NPs in-vivo toxicity were also tested to assess whether these NPs, would have high half-life in addition to their low cytotoxicity, enhancing NOS passive targeting to cancer cells. In addition, the selective release of NOS as an alkaloid in the acidic medium was tested to mimic what would happen in the vicinity of cancer tissues and this would increase NOS safety and efficacy during its use as anti-cancer agent.

Noscapine loaded biodegradable nanoparticles to treat breast cancer

BONACUCINA, Giulia;CESPI, MARCO;PERINELLI, DIEGO ROMANO;PALMIERI, Giovanni Filippo
2016-01-01

Abstract

Breast cancer is the most common malignancy in women worldwide. Therapeutic strategies currently involve a combination of surgery, radiotherapy, immunotherapy, hormone therapy and/or chemotherapy. The efficacy of a chemotherapeutic formulation depends on its ability to selectively target diseased tissue, overcome biological barriers, and intelligently respond to the disease environment to release cytotoxic agents. The development of a controlled and targeted drug delivery system may result in a more efficient and less harmful solution to overcome the limitations associated with conventional chemotherapy (Cho et al.). Recent studies have been focused on developing nanoscale delivery vehicles capable of controlling the release of chemotherapeutics directly inside cancer cells. Micellar like nanoparticles (NPs) are produced by the self-assembly of amphiphilic molecules into a structure with a hydrophobic core and an hydrophilic outer layer, with diameters generally less than 100 nm, allowing them to extravasate through the tumor vessels fenestrations. Moreover, their hydrophilic surfaces may shield them from immediate recognition by reticuloendothelial system (RES) leading to an increase in their circulation time. Many micellar formulations are currently under clinical evaluation for the treatment of cancer (e.g. doxorubicin, paclitaxel and epirubicin). Therefore, the aim of this study was to synthesize a series of linear-block and star-shaped copolymers based on polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL), and to formulate noscapine (NOS) loaded biodegradable NPs by the nanoprecipitation technique. After characterization of these NPs, the best formulae were tested for in-vitro release and cytotoxicity using MCF-7 breast cancer cells. Pharmacokinetic parameters and NPs in-vivo toxicity were also tested to assess whether these NPs, would have high half-life in addition to their low cytotoxicity, enhancing NOS passive targeting to cancer cells. In addition, the selective release of NOS as an alkaloid in the acidic medium was tested to mimic what would happen in the vicinity of cancer tissues and this would increase NOS safety and efficacy during its use as anti-cancer agent.
2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/399855
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