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Pharmaceutics 2018, 10(2), 52; https://doi.org/10.3390/pharmaceutics10020052

Wool-Like Hollow Polymeric Nanoparticles for CML Chemo-Combinatorial Therapy

1
Nanotechnology Institute, CNR-Nanotechnology Institute (CNR-NANOTEC), University La Sapienza, P.zle A. Moro, 00185 Roma, Italy
2
Nanotechnology Institute, CNR-Nanotechnology Institute (CNR-NANOTEC), Monteroni street, 73100 Lecce, Italy
*
Author to whom correspondence should be addressed.
Received: 23 March 2018 / Revised: 11 April 2018 / Accepted: 12 April 2018 / Published: 18 April 2018
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Abstract

Chronic myeloid leukaemia (CML) is caused by the BCR-ABL oncogene, which encodes the constitutively active BCR-ABL tyrosine kinase. Targeted therapy with tyrosine-kinase inhibitors induces a partial cytogenetic response in most patients. Nanosystems can represent an opportunity for combinatorial therapy with the capacity to simultaneously release different therapeutic agents, checking the pharmacokinetic properties. In this work, we have developed a novel poly-(ε-caprolactone) (PCL) nanosystem for combinatorial therapy in CML, composed of a biodegradable pH sensitive core releasing Nilotinib (Nil) and an enzymatic sensitive outer shell releasing Imatinib Mesylate (IM), resulting in wool-like nanoparticles (NPs). The resulting double loaded wool-like hollow PCL NPs showed a high dual-drug encapsulation efficiency, pH and enzymatic sensitivity and synchronized drug release capability. The combinatorial delivery of IM and Nil exhibited an importantly reduced IC50 value of IM and Nil on leukaemia cells compared to single free drugs administration. In vitro results, showed that combinatorial nanomixures preserved the biological activity of loaded drugs for extensive time windows and led to a constant release of active drug. In addition, the combination of IM and Nil in single PCL NPs have shown a more therapeutic efficiency at a low dose with respect to the single drug nanomixures, confirming that both drugs reached the target cell precisely, maximizing the cytotoxicity while minimizing the chances of cell resistance to drugs. View Full-Text
Keywords: combinatorial therapy; polymeric nanoparticles; CML cells combinatorial therapy; polymeric nanoparticles; CML cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cortese, B.; D’Amone, S.; Palamà, I.E. Wool-Like Hollow Polymeric Nanoparticles for CML Chemo-Combinatorial Therapy. Pharmaceutics 2018, 10, 52.

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