Effects of polymer molecular weight on relative oral bioavailability of curcumin

Abstract

Background: Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome. Methods: Curcumin encapsulated in low (5000-15,000) and high (40,000-75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsificationsolvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples. Results: There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (C max ) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 µg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC. Conclusion: Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods.

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

“…29 However, PGA-co-PCL has a high degree of hydrophobicity. 30 PGA-co-PCL NPs can be rapidly removed by the reticuloendothelial system when they are intravenously injected into the body. 31,32 These drawbacks can be overcome by introduced D-α-tocopheryl polyethylene glycol (PEG) 2000 succinate (TPGS 2k ) to PGA, PCL, and PGA-co-PCL.…”

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

“…4,[9][10][11][12][13] Our hypothesis is supported by previous studies that reported that encapsulated CUR with PLGA-based nanoparticles administrated orally to rats increased CUR levels in the plasma. [14][15][16][17][18] However, to the best of our knowledge, there are no data about CURG, despite the fact that it is the main metabolite of CUR found in the plasma. Therefore, it is not clear whether CUR nanoparticles (CUR-NP) actually improve the intestinal absorption of CUR.…”

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

“…35,36 Researchers have also investigated nanoscale formulations of curcumin, such as liposomes, microemulsions, and micelles, for potential therapeutic applications. [37][38][39][40][41][42] The nanoscale effect by which such drug delivery systems improve the oral performance of curcumin involves increasing the surface area and interactions of curcumin, thereby providing better water dispersibility to enhance its absorption. 38 In this study, a novel silica-coating liposomal strategy was used to construct a nanohybrid formulation for curcumin.…”

“…[37][38][39][40][41][42] The nanoscale effect by which such drug delivery systems improve the oral performance of curcumin involves increasing the surface area and interactions of curcumin, thereby providing better water dispersibility to enhance its absorption. 38 In this study, a novel silica-coating liposomal strategy was used to construct a nanohybrid formulation for curcumin. Silica-coated FLs were prepared by the dry-film dispersion method, combined with a sol-gel precipitation upon the liposomal surface.…”