Novel Ponatinib-Encapsulated Biomimetic Nanoparticle Formulation

This invention is a novel formulation of ponatinib which allows for targeted drug delivery to cancer cells. This formulation utilizes a biomimetic lipid-based nanoparticle platform embedded with leukocyte membrane proteins. Previous iterations of this platform have demonstrated that the addition of leukocyte membrane proteins improve the targeting effect of these biomimetic nanoparticles towards inflamed endothelium. Due to the hydrophobic nature of ponatinib, this platform was optimized in order to prepare a highly reproducible and non-operator dependent formulation which was able to encapsulate ponatinib. Preliminary studies of this biomimetic nanoscale ponatinib delivery system revealed that this formulation was able to control the release of ponatinib and efficiently kill cancer cells.

 

Stage of Development

 

In vitro data: Physical, chemical, and biological properties of the ponatinib-encapsulated biomimetic nanoparticles were characterized. These particles displayed similar size and morphology when compared to empty liposomes or biomimetic nanoparticles. Reproducibility studies indicated that the synthesis process was not operator dependent. Furthermore, nanoparticle uptake and cytotoxicity studies revealed that ponatinib-encapsulated liposomes and biomimetic nanoparticles showed similar cell killing responses in murine osteosarcoma cells compared to free ponatinib, indicating that this formulation does not inhibit or reduce the efficacy of the drug. 

 

Competitive Landscape

 

Nanotechnologies play a crucial role in advanced drug formulations due to their ability to target and control drug release in diseased tissues while defending the body from lethal off-target side effects. Among the different nanoparticle formulations, liposomes are frequently used because they are capable of encapsulating either hydrophilic or hydrophobic drugs in their core or membrane. However, due to low bilayer membrane space, encapsulation of hydrophobic materials such as ponatinib, has been limited. Moreover, previous studies demonstrated that liposomal biodistribution is limited due to mononuclear phagocytic system uptake and the lack of specific targeting moieties. These limitations result in liposomal accumulation in the body filtering organs, followed by off target drug release, and ultimately unwanted side effects. This invention addresses these limitations using a new formulation which is able to both improve the targeting capabilities of the nanoparticle using a biomimetic approach and improve the encapsulation efficiency of ponatinib.

 

Competitive Advantages

 

•       Increased ponatinib encapsulation efficiency

•       Reproducible manufacturing process

•       Similar uptake and cytotoxicity of cancer cells as free ponatinib

 

Patent Information:
Licensing Contact
Paige Glumac
pglumac@houstonmethodist.org

Inventors:
Francesca Taraballi
Assaf Zinger
Ennio Tasciotti
Tomoyuki Naoi
Gherardo Baudo