Reproducible and Characterized Method for Ponatinib Encapsulation into Biomimetic Lipid Nanoparticles as a Platform for Multi-Tyrosine Kinase-Targeted Therapy.
Ponatinib (Pon) is a multi-tyrosine kinase inhibitor that demonstrated high efficiency for treating cancer. However, severe side effects caused by Pon off-targeting effects prevent its extensive use. Using our understanding into the mechanisms by which Pon is transported by bovine serum albumin in the blood, we have successfully encapsulated Pon into a biomimetic nanoparticle (NP). This lipid NP (i.e., “leukosomes”) incorporates membrane proteins purified from activated leukocytes that enable immune evasion, and enhanced targeting of inflamed endothelium NPs have been characterized for their size, charge, and encapsulation efficiency. Membrane proteins enriched on the NP surface enabled modulation of Pon release. These NP formulations showed promising dose− response results on two different murine osteosarcoma cell lines, F420 and RF379.
“Our results indicate that our fabrication method is reproducible, nonuser-dependent, efficient in loading Pon, and applicable toward repurposing numerous therapeutic agents previously shelved due to toxicity profiles.”
In this study, we demonstrate that Pon can be successfully encapsulated into biomimetic lipid NP in a reproducible manner by independent operators using BSA. Moreover, in vitro data showed the ability of a Pon-loaded NP to kill murine OS cells. These results lay the foundation to justify additional work to further assess the therapeutic potential of a Pon biomimetic NP in in vivo model systems. In addition, our approach provides an efficient, methodical, and drug-specific method toward repurposing additional therapeutics previously disregarded due to toxicity profiles.