Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment

<i>Aims:</i> Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investiga...

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Main Authors: Chiara Dianzani, Chiara Monge, Gianluca Miglio, Loredana Serpe, Katia Martina, Luigi Cangemi, Chiara Ferraris, Silvia Mioletti, Sara Osella, Casimiro Luca Gigliotti, Elena Boggio, Nausicaa Clemente, Umberto Dianzani, Luigi Battaglia
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/5/1198
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author Chiara Dianzani
Chiara Monge
Gianluca Miglio
Loredana Serpe
Katia Martina
Luigi Cangemi
Chiara Ferraris
Silvia Mioletti
Sara Osella
Casimiro Luca Gigliotti
Elena Boggio
Nausicaa Clemente
Umberto Dianzani
Luigi Battaglia
author_facet Chiara Dianzani
Chiara Monge
Gianluca Miglio
Loredana Serpe
Katia Martina
Luigi Cangemi
Chiara Ferraris
Silvia Mioletti
Sara Osella
Casimiro Luca Gigliotti
Elena Boggio
Nausicaa Clemente
Umberto Dianzani
Luigi Battaglia
author_sort Chiara Dianzani
collection DOAJ
description <i>Aims:</i> Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. <i>Methods:</i> a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid<sup>®</sup>), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. <i>Results:</i> Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid<sup>®</sup>, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid<sup>®</sup>-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. <i>Conclusions:</i> In these preliminary studies, Intralipid<sup>®</sup> proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.
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spelling doaj.art-7773ce4cd8e24f249aa68c5a1b27a4452023-11-19T23:55:36ZengMDPI AGCancers2072-66942020-05-01125119810.3390/cancers12051198Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma TreatmentChiara Dianzani0Chiara Monge1Gianluca Miglio2Loredana Serpe3Katia Martina4Luigi Cangemi5Chiara Ferraris6Silvia Mioletti7Sara Osella8Casimiro Luca Gigliotti9Elena Boggio10Nausicaa Clemente11Umberto Dianzani12Luigi Battaglia13Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, ItalySan Giovanni Bosco Hospital, Piazza del Donatore di Sangue 3, 10154 Turin, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont (UPO), via Solaroli 17, 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont (UPO), via Solaroli 17, 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont (UPO), via Solaroli 17, 28100 Novara, ItalyDepartment of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont (UPO), via Solaroli 17, 28100 Novara, ItalyDepartment of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, Italy<i>Aims:</i> Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. <i>Methods:</i> a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid<sup>®</sup>), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. <i>Results:</i> Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid<sup>®</sup>, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid<sup>®</sup>-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. <i>Conclusions:</i> In these preliminary studies, Intralipid<sup>®</sup> proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.https://www.mdpi.com/2072-6694/12/5/1198nanoemulsionsIntralipid<sup>®</sup>temozolomiderapamycinbevacizumabmelanoma
spellingShingle Chiara Dianzani
Chiara Monge
Gianluca Miglio
Loredana Serpe
Katia Martina
Luigi Cangemi
Chiara Ferraris
Silvia Mioletti
Sara Osella
Casimiro Luca Gigliotti
Elena Boggio
Nausicaa Clemente
Umberto Dianzani
Luigi Battaglia
Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
Cancers
nanoemulsions
Intralipid<sup>®</sup>
temozolomide
rapamycin
bevacizumab
melanoma
title Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
title_full Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
title_fullStr Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
title_full_unstemmed Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
title_short Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
title_sort nanoemulsions as delivery systems for poly chemotherapy aiming at melanoma treatment
topic nanoemulsions
Intralipid<sup>®</sup>
temozolomide
rapamycin
bevacizumab
melanoma
url https://www.mdpi.com/2072-6694/12/5/1198
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