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Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy

Osteosarcoma (OSA) is the most frequently diagnosed primary malignant bone tumor in humans and dogs. In both species, standard chemotherapy can be limited by multidrug resistance of neoplastic cells, which prevents intracellular accumulation of cytotoxic drugs, resulting in chemotherapy failure. In...

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Autores principales: Chirio, Daniela, Sapino, Simona, Chindamo, Giulia, Peira, Elena, Vercelli, Cristina, Riganti, Chiara, Manzoli, Maela, Gambino, Graziana, Re, Giovanni, Gallarate, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322757/
https://www.ncbi.nlm.nih.gov/pubmed/35890258
http://dx.doi.org/10.3390/pharmaceutics14071362
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author Chirio, Daniela
Sapino, Simona
Chindamo, Giulia
Peira, Elena
Vercelli, Cristina
Riganti, Chiara
Manzoli, Maela
Gambino, Graziana
Re, Giovanni
Gallarate, Marina
author_facet Chirio, Daniela
Sapino, Simona
Chindamo, Giulia
Peira, Elena
Vercelli, Cristina
Riganti, Chiara
Manzoli, Maela
Gambino, Graziana
Re, Giovanni
Gallarate, Marina
author_sort Chirio, Daniela
collection PubMed
description Osteosarcoma (OSA) is the most frequently diagnosed primary malignant bone tumor in humans and dogs. In both species, standard chemotherapy can be limited by multidrug resistance of neoplastic cells, which prevents intracellular accumulation of cytotoxic drugs, resulting in chemotherapy failure. In this study, a lipophilic ester of doxorubicin (C12DOXO) was loaded into nanoparticles (NPs) using the “cold microemulsion dilution” method. The resulting NPs were then coated with calcium phosphate (CaP) in two different ways to have calcium or phosphate ions externally exposed on the surface. These systems were characterized by determining mean diameter, zeta potential, and drug entrapment efficiency; afterward, they were tested on human and canine OSA cells to study the role that the coating might play in increasing both drug uptake into tumor cells and cytotoxicity. Mean diameter of the developed NPs was in the 200–300 nm range, zeta potential depended on the coating type, and C12DOXO entrapment efficiency was in the 60–75% range. Results of studies on human and canine OSA cells were very similar and showed an increase in drug uptake and cytotoxicity for CaP-coated NPs, especially when calcium ions were externally exposed. Therefore, applications in both human and veterinary medicine can be planned in the near future.
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spelling pubmed-93227572022-07-27 Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy Chirio, Daniela Sapino, Simona Chindamo, Giulia Peira, Elena Vercelli, Cristina Riganti, Chiara Manzoli, Maela Gambino, Graziana Re, Giovanni Gallarate, Marina Pharmaceutics Article Osteosarcoma (OSA) is the most frequently diagnosed primary malignant bone tumor in humans and dogs. In both species, standard chemotherapy can be limited by multidrug resistance of neoplastic cells, which prevents intracellular accumulation of cytotoxic drugs, resulting in chemotherapy failure. In this study, a lipophilic ester of doxorubicin (C12DOXO) was loaded into nanoparticles (NPs) using the “cold microemulsion dilution” method. The resulting NPs were then coated with calcium phosphate (CaP) in two different ways to have calcium or phosphate ions externally exposed on the surface. These systems were characterized by determining mean diameter, zeta potential, and drug entrapment efficiency; afterward, they were tested on human and canine OSA cells to study the role that the coating might play in increasing both drug uptake into tumor cells and cytotoxicity. Mean diameter of the developed NPs was in the 200–300 nm range, zeta potential depended on the coating type, and C12DOXO entrapment efficiency was in the 60–75% range. Results of studies on human and canine OSA cells were very similar and showed an increase in drug uptake and cytotoxicity for CaP-coated NPs, especially when calcium ions were externally exposed. Therefore, applications in both human and veterinary medicine can be planned in the near future. MDPI 2022-06-27 /pmc/articles/PMC9322757/ /pubmed/35890258 http://dx.doi.org/10.3390/pharmaceutics14071362 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chirio, Daniela
Sapino, Simona
Chindamo, Giulia
Peira, Elena
Vercelli, Cristina
Riganti, Chiara
Manzoli, Maela
Gambino, Graziana
Re, Giovanni
Gallarate, Marina
Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title_full Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title_fullStr Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title_full_unstemmed Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title_short Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy
title_sort doxorubicin-loaded lipid nanoparticles coated with calcium phosphate as a potential tool in human and canine osteosarcoma therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322757/
https://www.ncbi.nlm.nih.gov/pubmed/35890258
http://dx.doi.org/10.3390/pharmaceutics14071362
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