TY - JOUR
T1 - Organic solvent-free preparation of keratin nanoparticles as doxorubicin carriers for antitumour activity
AU - Aluigi, Annalisa
AU - Ballestri, Marco
AU - Guerrini, Andrea
AU - Sotgiu, Giovanna
AU - Ferroni, Claudia
AU - Corticelli, Franco
AU - Gariboldi, Marzia Bruna
AU - Monti, Elena
AU - Varchi, Greta
N1 - Funding Information:
This work was also supported by the Investigator Grant of the Italian Association for Cancer Research (AIRC) 16740 to G.V. The authors acknowledge Lanificio Cariaggi Fine Yarns for the Merino Wool fibres supply. Appendix A
Publisher Copyright:
© 2018 Elsevier B.V.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Doxorubicin is one of the most effective chemotherapeutic agents for the treatment of several neoplastic conditions, such as leukemia, neuroblastoma, soft tissue and bone sarcomas, breast cancer, ovarian cancer and others. However, its clinical application is limited by cardiotoxicity, such as cardiomyopathy, that once developed carries a poor prognosis and is frequently fatal. The controlled release of doxorubicin by means of a smart carrier is a strategy to overcome the aforementioned drawback. Herein, doxorubicin/keratin nanoparticles were prepared by loading the drug through ionic gelation and aggregation methods, without using cross linkers, organic solvents neither surfactants. Both methodologies afford nanoparticles with yields up to 100 wt%, depending on the loading amount of doxorubicin. Although aggregation yield smaller nanoparticles (≈100 nm), ionic gelation allows a higher drug loading (up to 30 wt%,). More importantly, nanoparticles obtained through this procedure display a pH-responsive release of the drug: indeed Peppas-Salhin model suggests that, the doxorubicin release mechanism is predominantly controlled by diffusion at pH 7.4 and by protein swelling at pH 5. Moreover, nanoparticles prepared by ionic gelation resulted in more efficient cell killing of MDA-MB-231 and MCF-7 breast cancer cells than those prepared by aggregation. Based on the herein presented preliminary results, ionic gelation emerges as a promising approach for the preparation of keratin-based doxorubicin nanocarriers for cancer therapy, that is worth to further investigate.
AB - Doxorubicin is one of the most effective chemotherapeutic agents for the treatment of several neoplastic conditions, such as leukemia, neuroblastoma, soft tissue and bone sarcomas, breast cancer, ovarian cancer and others. However, its clinical application is limited by cardiotoxicity, such as cardiomyopathy, that once developed carries a poor prognosis and is frequently fatal. The controlled release of doxorubicin by means of a smart carrier is a strategy to overcome the aforementioned drawback. Herein, doxorubicin/keratin nanoparticles were prepared by loading the drug through ionic gelation and aggregation methods, without using cross linkers, organic solvents neither surfactants. Both methodologies afford nanoparticles with yields up to 100 wt%, depending on the loading amount of doxorubicin. Although aggregation yield smaller nanoparticles (≈100 nm), ionic gelation allows a higher drug loading (up to 30 wt%,). More importantly, nanoparticles obtained through this procedure display a pH-responsive release of the drug: indeed Peppas-Salhin model suggests that, the doxorubicin release mechanism is predominantly controlled by diffusion at pH 7.4 and by protein swelling at pH 5. Moreover, nanoparticles prepared by ionic gelation resulted in more efficient cell killing of MDA-MB-231 and MCF-7 breast cancer cells than those prepared by aggregation. Based on the herein presented preliminary results, ionic gelation emerges as a promising approach for the preparation of keratin-based doxorubicin nanocarriers for cancer therapy, that is worth to further investigate.
KW - Aggregation
KW - Doxorubicin
KW - Ionic gelation
KW - Keratin
KW - Nanoparticles
KW - Humans
KW - Solvents/chemistry
KW - Doxorubicin/chemistry
KW - Keratins/chemistry
KW - Drug Carriers/chemistry
KW - MCF-7 Cells
KW - Nanoparticles/chemistry
KW - Female
KW - Drug Delivery Systems/methods
KW - Hydrogen-Ion Concentration
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U2 - 10.1016/j.msec.2018.04.088
DO - 10.1016/j.msec.2018.04.088
M3 - Article
C2 - 29853116
AN - SCOPUS:85046459393
SN - 0928-4931
VL - 90
SP - 476
EP - 484
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
ER -