Galactosylated PLGA nanoparticles for the oral delivery of resveratrol: enhanced bioavailability and in vitro anti-inflammatory activity

Abstract

BackgroundResveratrol (RES) is a natural anti-inflammatory and antioxidant compound with poor water solubility and oral bioavailability. The present study takes the advantages of nanocarriers combined with a ligand (galactose) anchoring to orally deliver RES in an attempt to improve its bioavailability and pharmacological activity.MethodsRES-loaded galactosylated nanoparticles (RES-GNPs) were prepared by solvent diffusion technique using poly(lactic-co-glycolic acid), synthesized N-oleoyl-d-galactosamine and Tween 80. RES-GNPs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Oral bioavailability and in vitro anti-inflammatory activity were investigated in rats and lipopolysaccharides-induced RAW 264.7 cells, respectively.ResultsThe resulting RES-GNPs were 108.4 nm around in particle size with a polydispersity index of 0.217. Furthermore, RES-GNPs possessed a high EE and a slow drug release in water. After oral administration, RES-GNPs significantly enhanced the oral bioavailability of RES, up to 335.7% relative to RES suspensions. In situ single-pass intestinal perfusion and cellular uptake experiments showed that GNPs could improve the intestinal permeability and transcellular transport of RES. Moreover, the anti-inflammatory efficacy of RES-GNPs in RAW 264.7 cells model was superior to free RES and RES-GNPs.ConclusionThe results indicate that RES-GNPs can effectively promote the intestinal absorption of RES and strengthen its bioactivity, which may be a promising system for the treatment of inflammatory diseases.

Potential Adverse Effects of Resveratrol: A Literature Review

“…Solid lipid nanoparticles are novel drug carriers that can incorporate lipophilic drugs and improve their stability and bioavailability, water solubility, safety, bio-distribution, and biocompatibility [209]. Loading RE into poly-lactic-co-glycolic acid (PLGA) nanoparticles increased RE oral bioavailability up to 335.7%, in comparison to RE, alone following administration in rats [210]. Nanoparticle formulations even enhanced the therapeutic potential and efficacy of RE, especially its in vivo anti-cancer activities in several cancer types.…”

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Resveratrol-loaded PLGA nanoparticles exhibited an excellent and stable delivery with remarkable improvement in encapsulation efficiency, drug loading capacity, solubility, absorption, bioavailability, and sustained release of resveratrol to attenuate nonalcoholic fatty liver disease, which is very closely associated with type 2 diabetes [213]. Galactosylated PLGA has also been found to be a potential nanocarrier for the oral delivery of resveratrol to achieve improved bioavailability and therapeutic efficacy [214]. Oral treatment with resveratrol-assembled gold nanoparticles exhibited excellent inhibitory effects on the activation of vascular endothelial growth factor (VEGF)-1, monocyte chemotactic proteins-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), extracellular signal-regulated kinase (ERK) 1/2, NF-κB, TNFα, IL-6, IL-1β genes in the retina of diabetic rats [215].…”

“…Chemical modifications of polymeric nanocarriers can also improve the pharmacokinetic profile and compliance over unmodified polymers. Galactosylation of PLGA can yield superior nanocarrier in terms of improvement in transepithelial transport, oral bioavailability, and therapeutic efficacy of resveratrol than the unmodified PLGA [214]. Similarly, succinylated chitosan-alginate and o-hexadecyl-dextran blocks have been regarded as suitable nanocarriers for the oral delivery of naturally occurring antidiabetic molecules [224,256].…”

Nanodelivery of Natural Antioxidants: An Anti-aging Perspective

“…Resveratrol loaded in zein nanoparticles with bovine serum albumin-caffeic acid conjugate (particle size from 206 to 217 nm) was demonstrated to exert significantly higher cellular antioxidant activity than resveratrol alone (Fan et al, 2018a). Anti-inflammatory abilities of resveratrol-loaded nanoparticles, such as galactosylated poly(lactic-co-glycolic acid) nanoparticles, have been also reported (Siu et al, 2018).…”