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

[Display omitted] •FK506 was completely encapsulated in the spherical and uniform Soluplus-SNPs.•Phosphate buffer (50mM) induced FK506 Soluplus-SNPs to thermosensitive hydrogels.•FK506 Soluplus-SNPs hydrogels was sustainable in vitro and long retention in vivo.•FK506 Soluplus-SNPs hydrogels signific...

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Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-01, Vol.149, p.97-104
Main Authors: Wu, Huimin, Wang, Kaiyuan, Wang, Hanning, Chen, Fang, Huang, Wencong, Chen, Yuqi, Chen, Jiali, Tao, Jin, Wen, Xiaoguang, Xiong, Subin
Format: Article
Language:English
Subjects:
Animals
Arthritis
Arthritis, Experimental - drug therapy
Arthritis, Experimental - metabolism
Arthritis, Experimental - pathology
Crosslinking
Delivery systems
Drug Carriers
Drug Compounding
Drug Liberation
Edema - drug therapy
Edema - metabolism
Edema - pathology
Gelation
Hindlimb
Hydrogels
Hydrogels - chemistry
Immunosuppressive Agents - chemistry
Immunosuppressive Agents - pharmacokinetics
Immunosuppressive Agents - pharmacology
In vitro testing
Kinetics
Kolliphor P407
Male
Mice
Mice, Inbred ICR
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Particle Size
Phase Transition
Poloxamer - chemistry
Polyethylene Glycols - chemistry
Polyvinyls - chemistry
Rats
Rats, Sprague-Dawley
Rheumatoid arthritis
Self-assembled nanoparticles
Soluplus
Tacrolimus
Tacrolimus - chemistry
Tacrolimus - pharmacokinetics
Tacrolimus - pharmacology
Therapy
Thermosensitive hydrogels
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Summary:[Display omitted] •FK506 was completely encapsulated in the spherical and uniform Soluplus-SNPs.•Phosphate buffer (50mM) induced FK506 Soluplus-SNPs to thermosensitive hydrogels.•FK506 Soluplus-SNPs hydrogels was sustainable in vitro and long retention in vivo.•FK506 Soluplus-SNPs hydrogels significantly treated the AIA rats by local injection. 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±2.9nm. 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 (50mM, pH 7.4) was from 37.4±0.1°C to 32.8±0.3°C and the gelation time was not greater than 2min. Soluplus-SNPs gelling systems showed lower viscosity and wider range concentrations in sol state at 25°C and stronger gel strength at 37°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.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2016.10.013