PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment

The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be intern...

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Main Authors: Ana I. Fraguas-Sánchez, Ana I. Torres-Suárez, Marie Cohen, Florence Delie, Daniel Bastida-Ruiz, Lucile Yart, Cristina Martin-Sabroso, Ana Fernández-Carballido
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/12/5/439
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author Ana I. Fraguas-Sánchez
Ana I. Torres-Suárez
Marie Cohen
Florence Delie
Daniel Bastida-Ruiz
Lucile Yart
Cristina Martin-Sabroso
Ana Fernández-Carballido
author_facet Ana I. Fraguas-Sánchez
Ana I. Torres-Suárez
Marie Cohen
Florence Delie
Daniel Bastida-Ruiz
Lucile Yart
Cristina Martin-Sabroso
Ana Fernández-Carballido
author_sort Ana I. Fraguas-Sánchez
collection DOAJ
description The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC<sub>50</sub> values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant—tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-<i>co</i>-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.
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spelling doaj.art-5a5f09f0102742a9b9c3737e3a57e4172023-11-19T23:54:20ZengMDPI AGPharmaceutics1999-49232020-05-0112543910.3390/pharmaceutics12050439PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo AssessmentAna I. Fraguas-Sánchez0Ana I. Torres-Suárez1Marie Cohen2Florence Delie3Daniel Bastida-Ruiz4Lucile Yart5Cristina Martin-Sabroso6Ana Fernández-Carballido7Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, SpainDepartment of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, SpainDepartment of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, SwitzerlandDepartment of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, SwitzerlandDepartment of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, SwitzerlandDepartment of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, SpainDepartment of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, SpainThe intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC<sub>50</sub> values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant—tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-<i>co</i>-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.https://www.mdpi.com/1999-4923/12/5/439chorioallantoic membrane modelcannabinoidscannabidiolgynaecological cancernanomedicines
spellingShingle Ana I. Fraguas-Sánchez
Ana I. Torres-Suárez
Marie Cohen
Florence Delie
Daniel Bastida-Ruiz
Lucile Yart
Cristina Martin-Sabroso
Ana Fernández-Carballido
PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
Pharmaceutics
chorioallantoic membrane model
cannabinoids
cannabidiol
gynaecological cancer
nanomedicines
title PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
title_full PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
title_fullStr PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
title_full_unstemmed PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
title_short PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
title_sort plga nanoparticles for the intraperitoneal administration of cbd in the treatment of ovarian cancer in vitro and in ovo assessment
topic chorioallantoic membrane model
cannabinoids
cannabidiol
gynaecological cancer
nanomedicines
url https://www.mdpi.com/1999-4923/12/5/439
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