| Literature DB >> 25791805 |
Mark E Lobatto1, Claudia Calcagno2, Maarten J Otten2, Antoine Millon3, Sarayu Ramachandran2, Maarten P M Paridaans2, Fleur M van der Valk4, Gert Storm5, Erik S G Stroes4, Zahi A Fayad2, Willem J M Mulder1, Josbert M Metselaar6.
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. FROM THE CLINICAL EDITOR: 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.Entities:
Keywords: Atherosclerosis; Formulation design; GMP-grade; Nanomedicine; Prednisolone phosphate
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Year: 2015 PMID： 25791805 PMCID： PMC4495976 DOI： 10.1016/j.nano.2015.02.020
Source DB: PubMed Journal: Nanomedicine ISSN： 1549-9634 Impact factor: 5.307