Conclusion
The current work provided an encouraging and practical delivery system for novel Selenadiazoles and glutaminase allosteric inhibitors whose poor water-soluble characteristic has been a bottleneck for the field.
Methods
The CPD 23@SOL micelles were prepared, optimized and evaluated through on the basis of solubility improvement and loading capacity. Characterizations of particle size and Zeta potential by dynamic light scattering, morphology by transmission electron microscopy and solid state by X-ray powder diffraction were closely conducted. The biological studies included the tumor cell growth inhibition, blood and liver microsomal stability, in vivo pharmacokinetics and tissue biodistribution.
Results
At 1:20 ratio of CPD 23:SOL, CPD 23@SOL micelles were well-dispersed, spherical and stable, with size less than 200 nm with encapsulation efficiency of more than 90%. This SOL micellar system significantly increased the aqueous solubility of CPD 23 by 15,000 folds. Particularly, CPD 23@SOL micelles demonstrated higher stability in blood and liver microsomes, showing approximately 86% remaining at 2 h incubation and about 66% at 4 h, respectively. In addition, with or without micellar formulation, CPD 23 maintained essentially the same inhibitory activity in tumor cells. Interestingly, CPD 23@SOL micelles significantly improved the pharmacokinetic exposure, prolonged the in vivo circulation and dramatically changed tissue biodistributions of CPD 23.