1. Int J Pharm. 2010 Jun 15;392(1-2):20-8. Epub 2010 Mar 11.

Active and passive tumor targeting of a novel poorly soluble cyclin dependent
kinase inhibitor, JNJ-7706621.

Danhier F, Ucakar B, Magotteaux N, Brewster ME, Préat V.

Université Catholique de Louvain, Louvain Drug Institute, Brussels, Belgium.

The anti-cancer cyclin dependent kinase (CDK) inhibitors are poorly soluble
drugs. The aims of this work were (i) to formulate a novel CDK inhibitor,
JNJ-7706621, in polymeric micelles and nanoparticles, (ii) to compare passive and
active targeting on tumor growth and (iii) to evaluate the potential synergy of
JNJ-7706621 with Paclitaxel. Therefore, JNJ-7706621 was encapsulated in
self-assembling diblock copolymers made up of epsilon-caprolactone (CL) and
trimethylene carbonate (TMC) (PEG-p-(CL-co-TMC)) polymeric micelles and in
(poly(lactide-co-glycolide)) (PLGA)-based PEGylated nanoparticles (passive
targeting) as well as in RGD-grafted nanoparticles (active targeting). In vivo,
the transplantable liver tumor growth was more decreased by active targeting with
RGD-grafted nanoparticles than by passive targeting with micelles or ungrafted
nanoparticles. Moreover, a synergy between JNJ-7706621 and Paclitaxel was
demonstrated. Therefore, active targeting of JNJ-7706621-loaded nanocarriers may 
be considered as an effective anti-cancer drug delivery system for cancer
chemotherapy, particularly in combination with Paclitaxel. Copyright 2010
Elsevier B.V. All rights reserved.

PMID: 20226846 [PubMed - in process]