title: Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy.
abstract: The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100nm±10nm, with a prednisolone phosphate (PLP) incorporation efficiency of 3%-5%. Pharmacokinetics and toxicokinetics of GMP-grade liposomal nanoparticles were evaluated in healthy rats, which were compared to daily and weekly administration of free prednisolone phosphate, revealing a long circulatory half-life with minimal side effects. Subsequently, non-invasive multimodal clinical imaging after liposomal nanotherapy's intravenous administration revealed anti-inflammatory effects on the vessel wall of atherosclerotic rabbits. The present program led to institutional review board approval for two clinical trials with patients with atherosclerosis.
  
  
  BACKGROUND
  In drug discovery, bringing production to industrial scale is an essential process. In this article the authors describe the development of an anti-inflammatory nanoparticle according to good manufacturing practice. As a result, this paves the way for translating laboratory studies to clinical trials in humans.
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Mark E
authors: ME
authors: Lobatto
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
authors: Claudia
authors: C
authors: Calcagno
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
authors: Maarten J
authors: MJ
authors: Otten
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Department of Vascular Surgery, University Hospital of Lyon, Lyon, France.
authors: Antoine
authors: A
authors: Millon
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
authors: Sarayu
authors: S
authors: Ramachandran
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
authors: Maarten P M
authors: MP
authors: Paridaans
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Fleur M
authors: FM
authors: van der Valk
authors: Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Gert
authors: G
authors: Storm
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Erik S G
authors: ES
authors: Stroes
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
authors: Zahi A
authors: ZA
authors: Fayad
authors: Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Willem J M
authors: WJ
authors: Mulder
authors: Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands; Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany. Electronic address: jmetselaar@ukaachen.de.
authors: Josbert M
authors: JM
authors: Metselaar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D006207:Half-Life; D006801:Humans; D008081:Liposomes; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008081:Liposomes; C009022:prednisolone phosphate; D011239:Prednisolone
keywords: Atherosclerosis; Formulation design; GMP-grade; Nanomedicine; Prednisolone phosphate