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Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy.

Nanomedicine : nanotechnology, biology, and medicine (2015-03-21)
Mark E Lobatto, Claudia Calcagno, Maarten J Otten, Antoine Millon, Sarayu Ramachandran, Maarten P M Paridaans, Fleur M van der Valk, Gert Storm, Erik S G Stroes, Zahi A Fayad, Willem J M Mulder, Josbert M Metselaar
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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tantalum(V) ethoxide, 99.98% trace metals basis
Tantalum(V) ethoxide, packaged for use in deposition systems