Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy
2015
Lobatto, M. E. | Calcagno, C. | Otten, M. J. | Millon, A. | Ramachandran, S. | Paridaans, M. P. | Valk, F. M., | Storm, G. | Stroes, E. S. | Fayad, Z. A. | Mulder, W. J. | Metselaar, J. M.
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.
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