Design and evaluation of a solid dispersion and thermosensitive hydrogel combined local delivery system of dimethoxycurcumin

Abstract

Dimethoxycurcumin (DiMC) is an analogue of curcumin highlighted with its superior pro-oxidant potent, immunomodulatory property and anti-tumor activity. However, bioavailability of DiMC is low due to its poor water solubility. To address this issue, a solid dispersion (SD) and injectable thermosensitive hydrogel combined DiMC delivery system was developed. First, carriers including polyvinylpyrrolidone K30 (PVP–K30), polyethylene glycol 4000 (PEG-4000), and poloxamer-188 were used to prepare SDs at different drug/polymer weight ratios. DiMC incorporated PVP-K30 SD with ratio of 1:10 (DiMC-PVP (1:10) SD) showed the best DiMC solubility enhancement, in which crystalline DiMC was completely amorphorized after SD formation. After that, a SD incorporated injectable thermosensitive hydrogel (DSD-CSGP) with gelation temperature at 37 °C was formulated with DiMC-PVP (1:10) SD, chitosan, and β-sodium glycerophosphate (β-GP). Different ratios of chitosan/SD (w/w) and chitosan/β-GP (v:v) were studied to analyze their effects on hydrogel gelation and DiMC release behaviors. The hydrogel with chitosan/SD (w/w) at 2:1 and chitosan/β-GP (v:v) at 2:0.5 showed a gelation time less than 3 min, and a Peppas model fitted sustained DiMC release behavior. The released DiMC could significantly inhibit the growth of prostate cancer cells. These results suggested the developed DSD-CSGP can be a potential formula for DiMC localized delivery.