Novel self-assembled tacrolimus nanoparticles cross-linking thermosensitive hydrogels for local rheumatoid arthritis therapy

作者：Wu, Huimin; Wang, Kaiyuan; Wang, Hanning; Chen, Fang; Huang, Wencong; Chen, Yuqi; Chen, Jiali; Tao, Jin; Wen, Xiaoguang; Xiong, Subin^*

来源：Colloids and Surfaces B: Biointerfaces , 2017, 149: 97-104.

DOI：10.1016/j.colsurfb.2016.10.013

• Tacrolimus
• Self-assembled nanoparticles
• Thermosensitive hydrogels
• Soluplus
• Kolliphor P407
• Rheumatoid arthritis

The aim was to explore the potential application of novel self-assembled nanoparticles cross-linking thermosensitive hydrogels composed of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and tacrolimus (FK-506) for local therapy of rheumatoid arthritis (RA). The sol-gel transition temperature (Tsol-gel), gelation time, rheological behaviors, in vitro release, in vivo gelation and retention, and therapeutic efficacy against adjuvant-induced arthritis (AIA) rats were compared between the Soluplus hydrogels and widely studied poloxamer 407 (P407) delivery systems. In sol, the spherical and uniform FK506 loaded Soluplus nanoparticles (Soluplus-SNPs) were self-assembled with encapsulation efficiency of 99.5 +/- 1.5% and particle size of 73.9 +/- 2.9 nm. The decreased Tsol-gel of Soluplus-SNPs hydrogels was associated with the addition of salts, elevation of pH and ionic strength. The optimal Tsol-gel of Soluplus-SNPs with concentrations of 10%-30% in phosphate buffer (50 mM, pH 7.4) was from 37.4 +/- 0.1 degrees C to 32.8 +/- 0.3 degrees C and the gelation time was not greater than 2 min. Soluplus-SNPs gelling systems showed lower viscosity and wider range concentrations in sol state at 25 degrees C and stronger gel strength at 37 degrees C than P407, which resulting in longer sustained release of FK506 but without burst-release in vitro, and longer retention time in the local injection site in vivo. The therapeutic efficacy to treat AIA rats was significantly enhanced from d10 to d17 after a single dose of FK506 loaded in 10% and 20% Soluplus-SNPs hydrogels. In conclusion, Soluplus-SNPs hydrogel is a potential sustainable delivery system for FK506 to treat RA locally.

• 出版日期2017-1-1
• 单位浙江工业大学