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

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.
AuthorsFabienne Danhier, Bernard Ucakar, Nicolas Magotteaux, Marcus E Brewster, Véronique Préat
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 392 Issue 1-2 Pg. 20-8 (Jun 15 2010) ISSN: 1873-3476 [Electronic] Netherlands
PMID20226846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • JNJ-7706621
  • Lactones
  • Micelles
  • Polyesters
  • Protein Kinase Inhibitors
  • TMC-ECL copolymer
  • Triazoles
  • Polyglactin 910
  • Cyclin-Dependent Kinases
  • Paclitaxel
  • Animals
  • Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
  • Apoptosis (drug effects)
  • Cell Survival (drug effects)
  • Cyclin-Dependent Kinases (antagonists & inhibitors)
  • Dose-Response Relationship, Drug
  • Drug Carriers (chemistry)
  • Drug Compounding
  • Drug Synergism
  • HeLa Cells
  • Humans
  • Lactones (chemistry)
  • Liver Neoplasms, Experimental (drug therapy)
  • Mice
  • Mice, Inbred Strains
  • Micelles
  • Nanoparticles
  • Paclitaxel (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
  • Particle Size
  • Polyesters (chemistry)
  • Polyglactin 910 (chemistry)
  • Protein Kinase Inhibitors (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
  • Solubility
  • Surface Properties
  • Triazoles (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: