The paper presents a study using silk nano- and microparticles as carriers to deliver curcumin (CUR), a multifunctional and efficient, yet water-insoluble, antioxidant, with the primary goal of enhancing bioavailability. CUR-loaded silk nanoparticles were prepared by emulsification, resulting in particle sizes ranging from 229 to 2286 nm in diameter, with loading efficiencies from 22 to 41%. The encapsulation mechanism involved hydrophobic interaction between the β-sheet structure fabricated from the silk and the phenol groups of curcumin. In vitro studies revealed that curcumin was released more slowly from the larger particles than the smaller particles. An HPLC-MS/MS method was developed to determine the content of curcumin in rat plasma. The particles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with those of plain curcumin crystals. After 24 h, the larger silk particles (CSN-800, CUR-silk nanoparticles with sizes ∼800 nm) showed longer plasma circulation time for CUR (Tmax was 1.76 ± 0.10 h) when compared with that of the smaller silk particles (CSN-200 with sizes ∼200 nm, Tmax was 1.17 ± 0.07 h). The Cmax of CSN-200 was 3-fold greater than that of CSN-800. By contrast to the groups of plain CUR (without silk particles), CSN-200 and CSN-800 increased CUR bioavailability 17- and 5- fold, respectively. When mixtures of CSN-200 and CSN-800 at different ratios were orally administered to rats, medium bioavailability (>13 times) and exposure time (T1/2 > 1.68 h) were obtained. These results elucidated the effect of CUR-silk particle sizes on bioavailability after oral delivery, as a basis for future applications.
Keywords: bioavailability; curcumin; nanoparticles; polyethylene glycol; silk.