Oral Delivery of Curcumin Using Silk Nano- and Microparticles

Abstract

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 (T max was 1.76 ± 0.10 h) when compared with that of the smaller silk particles (CSN-200 with sizes ∼200 nm, T max was 1.17 ± 0.07 h). The C max 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 (T 1/2 > 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.

Fabrication of Thymoquinone‐Loaded Albumin Nanoparticles by Microfluidic Particle Synthesis and Their Effect on Planarian Regeneration

“…Nanoparticles are drug delivery systems that can provide sustained, controlled, and targeted drug delivery to enhance therapeutic effects and reduce side effects . The encapsulation of hydrophobic drugs in nanoparticles improves their bioavailability, protects the drugs from external factors, limits their diffusion to normal tissues, and prevents their rapid metabolism …”

“…[13,14] The encapsulation of hydrophobic drugs in nanoparticles improves their bioavailability, protects the drugs from external factors, limits their diffusion to normal tissues, and prevents their rapid metabolism. [15][16][17] Most common methods for nanoparticle production are batch processes, which use traditional beaker methods and are designed for mass production. In these systems, local variations have a significant effect on the particle formation process and usually produce particles with broad size distributions as a result of limited control on the particle formation.…”

Fibroin nanoparticles: a promising drug delivery system

“…Conversely, the C max of 200-nm FNPs was twofold greater than that of the 800-nm FNPs (446.43 ± 142.18 vs. 228.05 ± 46.73 ng/mL). Remarkably, the 200-nm FNPs increased curcumin bioavailability up to 17 times higher than the pure drug, as well as doubled its halflife from 0.89 ± 0.21 h to 1.51 ± 0.23 h (Wu et al, 2018). Roy et al formulated FNPs from the Samia cynthia ricini silkworm (another species in the Lepidoptera order) using the bead milling method to deliver anticancer milk proteins bovine lactoferrin for the purpose of breast cancer treatment (Roy et al, 2016).…”

“…These include high water solubility, biodegradability and biocompatibility, ease of fabrication, freeze-drying favorability, high drug entrapment efficiency and drug loading capacity, controllable particles sizes and release profiles, and modifiable surface (Xie et al, 2006;Qu et al, 2014;Tian et al, 2014;Li et al, 2016;Gianak et al, 2019;Pham et al, 2019a). Similar to the pure fibroin, FNPs also show excellent safety and biocompatibility in various applications, both in vitro and in vivo (Kim et al, 2015;Wu et al, 2018;Pham et al, 2019b;Takeuchi et al, 2019). To the best of our knowledge, the earliest FNP formulation was prepared using the desolvation (coacervation, nanoprecipitation) method, reported by Zhang et al (2007).…”

“…In another in vivo study, curcumin loaded FNPs were also utilized for the investigation of the relationship between particle size and the drug pharmacokinetic profiles (Wu et al, 2018). By using the polymer blending method with PEG 10,000 at various fibroin concentrations, the particle size ranging from 229 to 2286 nm, and the entrapment efficiencies from 22 to 41%, proportionally to the fibroin amount, were obtained.…”