Step-by-step optimization of a colchicine-loaded nanoemulgel for superior topical therapy of acute gouty arthritis.

A colchicine-loaded nanoemulgel (COL-nEMG) was developed for rapid and potent topical therapy of acute gouty arthritis (AGA). An O/W COL-loaded nanoemulsion (COL-nEMS, 14.20 ± 1.73 nm) was first prepared and optimized step by step, including excipient screening, pseudo-ternary phase diagram, in vitro transdermal delivery and D-optimal design. The optimized COL-nEMS containing 10% isosorbide dimethyl ether (DMI) was then dispersed into a gel matrix to produce the final COL-loaded nanoemulgel (COL-nEMG-DMI10). COL-nEMG-DMI10 exhibited a homogeneous appearance, favorable rheological properties, stable three-dimensional porous structure, and good storage stability with a steady-state transdermal flux of 54.6 ± 3.7 µg/cm²/h and 8 h cumulative permeation amount of 425.6 ± 28.3 µg/cm². In an AGA mouse model, COL-nEMG-DMI10 demonstrated rapid therapeutic effects with joint swelling inhibition rate (JSIR) of 37.0 ± 3.4% and maximum possible effect of 37.5 ± 5.3% at 1 h post-administration. In addition, COL-nEMG-DMI10 significantly suppressed the levels of local inflammatory cytokines, including TNF-α and IL-1β, in the ankle joints of AGA animals. This COL-nEMG-DMI10 topical formulation provides a promising treatment strategy for AGA with rapid and pronounced therapeutic efficacy.