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.

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

Chirio, Daniela
First
;
Sapino, Simona
;
Chindamo, Giulia;Peira, Elena;Vercelli, Cristina;Riganti, Chiara;Manzoli, Maela;Gambino, Graziana;Re, Giovanni;Gallarate, Marina
Last
2022

Abstract

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.
14
7
1362
1378
calcium phosphate coating; canine osteosarcoma; cytotoxicity; doxorubicin; human osteosarcoma; microemulsion; nanoparticles; uptake
Chirio, Daniela; Sapino, Simona; Chindamo, Giulia; Peira, Elena; Vercelli, Cristina; Riganti, Chiara; Manzoli, Maela; Gambino, Graziana; Re, Giovanni; Gallarate, Marina
File in questo prodotto:
File Dimensione Formato  
pharmaceutics-14-01362-v2.pdf

Accesso aperto

Dimensione 3.07 MB
Formato Adobe PDF
3.07 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1873043
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact