Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability

Abstract

There are many kinds of biological activities of resveratrol itself, but its clinical application is limited by its poor solubility in water and low bioavailability. Therefore, we have prepared glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles (GL-HSA-RESNPs). The purpose of this study was to investigate the bioavailability, pharmacokinetics and tissue distribution of resveratrol in rats after single-dose tail vein injection administration of GL-HSA-RESNPs. A sensitive and reliable high performance liquid chromatography (HPLC) method was established to verify the content of resveratrol in rat plasma and organs. The C max value after GL-HSA-RESNPs administration was significantly higher than that of resveratrol suspension (933 ± 76.64 ng/mL vs. 618 ± 42.54 ng/mL, p < .01). The T max value obtained after GL-HSA-RESNPs administration was significantly shorter than that after resveratrol suspension administration (0.17 ± 0.01 h vs. 0.25 ± 0.01 h, p < .001). The bioavailability of GL-HSA-RESNPs was 4.25 times higher than that of the pure resveratrol. The concentration of resveratrol in the main organs of rats treated with the GL-HSA-RESNPs was higher than that in rats treated with the pure resveratrol. Rats treated with GL-HSA-RESNPs had the highest concentration of resveratrol in their liver. It is indicated that GL-HSA-RESNPs is a promising liver-targeted delivery system that improves the in vivo bioavailability of resveratrol.

Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative breast cancer

“…In previous work, at 6 ​h after intragastric administration of Res in pig, most of Res metabolized to Res derived metabolites and approximately only 15% of the initial Res administered was recovered in the pig intestine [ 37 ]. Additionally, Res in rats after single-dose tail vein injection administration of Res excreted almost over 80% in the urine within 4 ​h [ 38 ].…”

Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism

“…Resveratrol’s application in living organisms is hindered by its low bioavailability, rapid metabolism, and pharmacokinetics [ 156 , 345 , 346 , 386 ]. Nevertheless, rapid progress is being made in new delivery systems to increase the efficacy of resveratrol [ 362 , 363 , 364 , 365 , 366 , 367 , 368 , 369 ]; this could contribute to the application of resveratrol in cancer treatment in the context of personalized medicine.…”

“…As detailed in Table 6 , various approaches to improving resveratrol’s biological efficacy, such as self-emulsifying drug delivery systems [ 362 ], liquid micellar formulations [ 363 ], layer-by-layer nano formulations [ 364 ], oat protein-shellac nanoparticles [ 365 ], casein nanoparticles [ 366 ], and nanocrystals [ 367 ], have yielded promising results. Selective organ targeting is also possible with resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles (targeting the liver) [ 368 ] and trans -resveratrol-loaded mixed micelles (targeting the brain) [ 369 ].…”

Synthesis and characterization of levan hydrogels and their use for resveratrol release

“…Resveratrol (trans-3,5,4′-trihydroxy-stilbene) is a polyphenolic compound isolated from grapes, peanuts and Polygonum cuspidatum roots and have anti-carcinogenic, anti-inflammatory, anti-oxidant, anti-obesity, analgesic, age-defying, lipoprotein regulatory, and platelet aggregation inhibitory properties and it is used as a natural medicine or nutraceutical in cardiovascular, metabolic and degenerative diseases, wound inflammation, pain reduction, infection prevention, and UV-radiation damage in skin cancer treatments. 10–13 Despite all the reported pharmacological benefits, resveratrol has limited applications due to its poor water solubility, poor stability in solutions, short half-life as well as its weakened therapeutic effect due to poor absorption and photo-instability. 13,14 To overcome these limitations and widen its applications, designing of delivery systems for resveratrol by use of liposomes, polymer-based nanoparticles and hydrogels is a highly preferred strategy.…”

“…10–13 Despite all the reported pharmacological benefits, resveratrol has limited applications due to its poor water solubility, poor stability in solutions, short half-life as well as its weakened therapeutic effect due to poor absorption and photo-instability. 13,14 To overcome these limitations and widen its applications, designing of delivery systems for resveratrol by use of liposomes, polymer-based nanoparticles and hydrogels is a highly preferred strategy. There are numerous nano/microparticulate systems for resveratrol delivery, however, scale-up infeasibility, production cost, skin irritation, low skin permeability, photo degradation, and low stability of nanocarriers limits their uses.…”