Intra-articular formulation of colchicine loaded nanoemulsion systems for enhanced locoregional drug delivery: in vitro characterization, 99mTc coupling and in vivo biodistribution studies

Abstract

Colchicine (Col) is a drug used mainly for prevention and treatment of acute gouty arthritis. Unfortunately, colchicine has a narrow therapeutic index, with no obvious differentiation between toxic and nontoxic doses, resulting in a great deal of doubt and a disappointing outcome. To surmount such limitation, colchicine nanoemulsion systems (ColNE) were developed using water titration technique. The pseudoternary phase diagrams of surfactant (Span 20 or Span 60 or Tween 80), cosurfactant (ethanol) and oil (IPM) were constructed. The developed ColNE systems were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP) and entrapment efficiency (EE %). ColNE-5 was selected as optimized system with PS = 103.34 ± 5.44 nm, ZP = 34.23 ± 0.94 mV, PDI = 0.26 ± 0.01% and EE % = 75.65 ± 0.34%. To track ColNE-5 in vivo, technetium 99 m (99mTc) was incorporated into this system via coupling with colchicine. 99mTc-ColNE-5 and 99mTc-Col solution (99mTc-ColS) were injected intra-articularly (IA) into the inflamed knee joint of Swiss albino mice joints stimulated by MSU crystals then the biodistribution pattern was studied. The findings revealed that IA injection of 99mTc-ColNE-5 significantly enhanced retention and the pharmacodynamic effects of Col compared to 99mTc-ColS. Herein, we concluded that nanoemulsion (NE) could be used as an IA injectable delivery vehicle to improve retention and localization of Col inside the inflamed joint.