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.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/7/1
Y1 - 2015/7/1
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 100. nm. ±. 10. nm, 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.
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 100. nm. ±. 10. nm, 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.
KW - Atherosclerosis
KW - Formulation design
KW - GMP-grade
KW - Nanomedicine
KW - Prednisolone phosphate
UR - http://www.scopus.com/inward/record.url?scp=84931034792&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2015.02.020
DO - 10.1016/j.nano.2015.02.020
M3 - Article
C2 - 25791805
AN - SCOPUS:84931034792
SN - 1549-9634
VL - 11
SP - 1133
EP - 1140
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 5
ER -