title: Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth in vivo.
abstract: BACKGROUND
  The inflammatory tumor microenvironment, and more specifically the tumor-associated macrophages, plays an essential role in the development and progression of prostate cancer towards metastatic bone disease. Tumors are often characterized by a leaky vasculature, which - combined with the prolonged circulation kinetics of liposomes - leads to efficient tumor localization of these drug carriers, via the so-called enhanced permeability and retention (EPR) -effect. In this study, we evaluated the utility of targeted, liposomal drug delivery of the glucocorticoid dexamethasone in a model of prostate cancer bone metastases.
  
  
  METHODS
  Tumor-bearing Balb-c nu/nu mice were treated intravenously with 0.2-1.0-5.0 mg/kg/week free- and liposomal DEX for 3-4 weeks and tumor growth was monitored by bioluminescent imaging.
  
  
  RESULTS
  Intravenously administered liposomes localize efficiently to bone metastases in vivo and treatment of established bone metastases with (liposomal) dexamethasone resulted in a significant inhibition of tumor growth up to 26 days after initiation of treatment. Furthermore, 1.0 mg/kg liposomal dexamethasone significantly outperformed 1.0 mg/kg free dexamethasone, and was found to be well-tolerated at clinically-relevant dosages that display potent anti-tumor efficacy.
  
  
  CONCLUSIONS
  Liposomal delivery of the glucocorticoid dexamethasone inhibits the growth of malignant bone lesions. We believe that liposomal encapsulation of dexamethasone offers a promising new treatment option for advanced, metastatic prostate cancer which supports further clinical evaluation.
authors: Department of Urology, Leiden University Medical Center, Leiden, The Netherlands; Department of Targeted Therapeutics, MIRA Institute for Biological Technology and Technical Medicine, Enschede, The Netherlands.
authors: Jan
authors: J
authors: Kroon
authors: Jeroen T
authors: JT
authors: Buijs
authors: Geertje
authors: G
authors: van der Horst
authors: Henry
authors: H
authors: Cheung
authors: Maaike
authors: M
authors: van der Mark
authors: Louis
authors: L
authors: van Bloois
authors: Larissa Y
authors: LY
authors: Rizzo
authors: Twan
authors: T
authors: Lammers
authors: Rob C
authors: RC
authors: Pelger
authors: Gert
authors: G
authors: Storm
authors: Gabri
authors: G
authors: van der Pluijm
authors: Josbert M
authors: JM
authors: Metselaar
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008081:Liposomes; D003907:Dexamethasone
keywords: bone metastasis; dexamethasone; drug delivery; liposomes; nanomedicine; prostate cancer