Objective: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol^®HS15 (SSCMs) to enhance curcumin’s solubility and thus oral bioavailability. Methods: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. Key findings: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol^®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol^®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin’s oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. Conclusions: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol^®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.

Genistein (GEN), is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus^® and Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN’s poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus^®:TPGS). The mean particle size of GEN-M was 184.7 ± 2.8 nm, with a narrow polydispersity index (PDI) of 0.162 ± 0.002. The zeta potential value of GEN-M was −2.92 ± 0.01 mV. The micelles solutions was transparent with blue opalescence has high the entrapment efficiency (EE) and drug loading (DL) of 97.12 ± 2.11 and 3.87 ± 1.26%, respectively. GEN-M was demonstrated a sustained release behavior when formed micelles shown in drug release in vitro. The solubility of GEN in water increased to 1.53 ± 0.04 mg/mL after encapsulation. The permeability of GEN across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of GEN-M showed a 2.42-fold increase in relative oral bioavailability compared with free GEN. Based on these findings, we conclude that this novel nanomicelles drug delivery system could be leveraged to deliver GEN and other hydrophobic drugs.

Objectives: With the purpose of developing a curcumin phospholipid complex (CPC) formulation with high performance, the CPC was prepared and solidified with Soluplus® in this study. Methods: Soluplus® was used as a carrier to solidify CPC. The structures of the CPC and curcumin phospholipid complex – Soluplus® solidified powder (CSP) – were also characterized by differential scanning electron microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffractometer, and flowability, in-vitro dissolution and oral bioavailability were also investigated. Key findings: All analysis indicated that curcumin was completely converted from crystalline to amorphous state in solidified powder. The angle of repose calculated in flowability study indicated a marked improvement from ‘cannot be measured’ to ‘37°’. Meanwhile, the dissolution study showed that in phosphate buffer condition, the dissolution rate of CSP had released 76.34% in pH 6.8 and the 78.19% in pH 1.2. Furthermore, in pharmacokinetic study, significant (P < 0.01) improvement of AUC0–∞ value was observed between CPC and CSP groups, and the results showed that AUC0–∞ value was increased from 205.84 ± 50.46 μg h/ml to 330.47 μg h/ml. Conclusions: A simple and convenient solidifying process was used in this study, and the data suggested that this process not only could improve the flowability and dissolution of phospholipid complex, but also increased the oral bioavailability of curcumin.