TY - JOUR
T1 - Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy
AU - Lobatto, Mark E.
AU - Calcagno, Claudia
AU - Otten, Maarten J.
AU - Millon, Antoine
AU - Ramachandran, Sarayu
AU - Paridaans, Maarten P. M.
AU - van der Valk, Fleur M.
AU - Storm, Gert
AU - Stroes, Erik S. G.
AU - Fayad, Zahi A.
AU - Mulder, Willem J. M.
AU - Metselaar, Josbert M.
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.nano.2015.02.020
DO - https://doi.org/10.1016/j.nano.2015.02.020
M3 - Article
C2 - 25791805
SN - 1549-9634
VL - 11
SP - 1133
EP - 1140
JO - Nanomedicine: Nanotechnology, Biology and Medicine
JF - Nanomedicine: Nanotechnology, Biology and Medicine
IS - 5
ER -