Nanomedicines for Inflammatory Arthritis: Head-to-Head Comparison of Glucocorticoid-Containing Polymers, Micelles, and Liposomes

被引:153
作者
Quan, Lingdong [1 ]
Zhang, Yijia [1 ]
Crielaard, Bart J. [2 ]
Dusad, Anand [1 ]
Lele, Subodh M. [3 ]
Rijcken, Cristianne J. F. [4 ]
Metselaar, Josbert M. [5 ]
Kostkova, Hana [6 ]
Etrych, Tomas [6 ]
Ulbrich, Karel [6 ]
Kiessling, Fabian [7 ,8 ]
Mikuls, Ted R. [9 ,10 ]
Hennink, Wim E. [2 ]
Storm, Gert [2 ,5 ]
Lammers, Twan [2 ,5 ,7 ,8 ]
Wang, Dong [1 ]
机构
[1] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, NL-3584 CG Utrecht, Netherlands
[3] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA
[4] Cristal Delivery BV, NL-6229 EV Maastricht, Netherlands
[5] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Targeted Therapeut, NL-7500 AE Enschede, Netherlands
[6] Inst Macromol Chem AS CR, Vvi, Prague 16206 6, Czech Republic
[7] Rhein Westfal TH Aachen, Univ Clin, Dept Expt Mol Imaging, D-52074 Aachen, Germany
[8] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, D-52074 Aachen, Germany
[9] Omaha VA Med Ctr, Omaha, NE 68198 USA
[10] Univ Nebraska Med Ctr, Dept Internal Med, Div Rheumatol, Omaha, NE 68198 USA
基金
欧洲研究理事会;
关键词
nanomedicine; drug targeting; inflammation; rheumatoid arthritis; glucocorticoid; dexamethasone; liposome; micelle; HPMA copolymer; HUMAN TUMOR XENOGRAFT; RHEUMATOID-ARTHRITIS; MACROMOLECULAR PRODRUG; THERAPEUTIC-EFFICACY; HPMA COPOLYMERS; RAT MODEL; DEXAMETHASONE; PHOSPHATE; DISEASES; RELEASE;
D O I
10.1021/nn4048205
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-cross-linked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow), and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single is. injection, the formulations with the slower drug release kinetics (le., M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research.
引用
收藏
页码:458 / 466
页数:9
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