Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile
- Hrkach, J.
- Von Hoff, D.
- Ali, M.
- Andrianova, E.
- Auer, J.
- Campbell, T.
- De Witt, D.
- Figa, M.
- Figueiredo, M.
- Horhota, A.
- Low, S.
- McDonnell, K.
- Peeke, E.
- Retnarajan, B.
- Sabnis, A.
- Schnipper, E.
- Song, J.
- Song, Y.
- Summa, J.
- Tompsett, D.
- et al.
DOIAbstract
We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver ...
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