Glucocorticoid-loaded core-cross-linked polymeric micelles with tailorable release kinetics for targeted therapy of rheumatoid arthritis.
Polymerizable and hydrolytically cleavable dexamethasone (DEX, red dot in picture) derivatives were covalently entrapped in core-cross-linked polymeric micelles that were prepared from a thermosensitive block copolymer (yellow and gray building block). By varying the oxidation degree of the thioether in the drug linker, the release rate of DEX could be controlled. The DEX-loaded micelles were used for efficient treatment of inflammatory arthritis in two animal models.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Bart J
BJ
Crielaard
Cristianne J F
CJ
Rijcken
Lingdong
L
Quan
Steffen
S
van der Wal
Isil
I
Altintas
Martin
M
van der Pot
John A W
JA
Kruijtzer
Rob M J
RM
Liskamp
Raymond M
RM
Schiffelers
Cornelus F
CF
van Nostrum
Wim E
WE
Hennink
Dong
D
Wang
Twan
T
Lammers
Gert
G
Storm
D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D007773:Lactates / Q000737:chemistry; D051379:Mice; D008823:Micelles; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D013440:Sulfides / Q000737:chemistry
D000178:Acrylamides; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D007773:Lactates; D008823:Micelles; D013440:Sulfides; C509680:poly(N-(2-hydroxypropyl) methacrylamide lactate); D011092:Polyethylene Glycols; D003907:Dexamethasone