Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol
Impact Factor: 4.761

A hindsight reflection on the clinical studies of poly( l ‐glutamic acid)‐paclitaxel

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Chemotherapy for cancer treatment is limited by the excessive toxicity to normal tissues. The design of chemodrug‐loaded nanoformulations provides a unique approach to improve the treatment efficacy while minimizing toxicity. Despite the numerous publications of nanomedicine for the last several decades, however, only a small fraction of the developed nanoformulations have entered clinical trials, with even fewer being approved for clinical application. Poly(l‐glutamic acid)‐paclitaxel (PG‐TXL) belongs to the few formulations that reached phase III clinical trials. Unfortunately, the development of PG‐TXL stopped in 2016 due to the inability to show significant improvement over current standard care. This review will provide an overview of the preclinical and clinical evaluations of PG‐TXL, and discuss lessons to be learned from this ordeal. The precise identification of suitable patients for clinical trial studies, deep understanding of the mechanisms of action, and an effective academic‐industry partnership throughout all phases of drug development are important for the successful bench‐to‐bedside translation of new nanoformulations.

Structures of poly(l‐glutamic acid)‐paclitaxel (PG‐TXL), its pharmacokinetics and tumor uptake. (a) Chemical structure of PG‐TXL (Reprinted with permission from Ref . Copyright 2008 Elsevier). (b) Area under the blood concentration–time (AUC) curves of PG‐TXL in three clinical studies: 1052, PGT101, and PGT105 (Reprinted with permission from Ref . Copyright 2005 Elsevier). (c) Comparison of tumor uptake between PG‐TXL and TXL in a murine OCa‐1 xenograft model. (Reprinted with permission from Ref . Copyright 2000 Springer)
[ Normal View | Magnified View ]
(a) T1‐weighted spin echo image of an Oca‐1 ovarian tumor acquired at 2 days after intravenous injection of PG‐Gd at a dose of 0.04 mmol Gd/kg. Arrows show area of tumor with contrast enhancement (Reprinted with permission from Ref . Copyright 2010 Elsevier). (b) Representative T1‐weighted fast spoiled gradient echo images of a rhesus monkey before contrast injection and at 2 h, 2 days, and 8 days after intravenous injection of PG‐Gd at 0.02 mmol Gd/kg. Enhancements of blood vessel, heart (not shown), and kidney (not shown) were clearly visualized at 2 h after PG‐Gd injection. By 8 days post‐injection, almost all contrast agent was cleared from all major organs (Reprinted with permission from Ref . Copyright 2011 John Wiley and Sons)
[ Normal View | Magnified View ]
Representative in vivo near‐infrared fluorescence (NIRF) images of cathepsin B activity in intracranially inoculated U87/TGL tumors. The mice used in the study had the same tumor burden as indicated by bioluminescence signal generated after intravenous injection of luciferin. NIRF images were acquired 24 h after intravenous injection of L‐PG‐NIR813 or D‐PG‐NIR813 with the same NIR dye payload (10%). (Reprinted with permission from Ref . Copyright 2007 Springer)
[ Normal View | Magnified View ]

Browse by Topic

Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Biology-Inspired Nanomaterials > Peptide-Based Structures
Therapeutic Approaches and Drug Discovery > Oncologic Disease

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts

In the Spotlight

Mauro Ferrari

Mauro Ferrari

started out in mechanical engineering and became interested in nanotechnology with his studies on nanomechanics and nanofluidics. His research work and involvement with setting up some of the premier nano centers and alliances in the world, bringing together universities, hospitals, and federal agencies, showcases interdisciplinarity at work.

Learn More