Improving water dispersibility and bioavailability of luteolin using microemulsion system

Abstract

We have studied the physiological effects and health functions of luteolin, especially focusing on its absorption and metabolism. Recent studies have reported the advantages of microemulsion to improve the bioavailability of poorly water-soluble compounds, including luteolin. In the present study, we aimed to evaluate the absorption and metabolic profile of luteolin delivered in microemulsion system via oral intake. First, we prepared water-dispersed luteolin (WD-L) using a microemulsion-based delivery system and confirmed that WD-L has superior water dispersibility compared to free luteolin (CO-L) based on their particle size distributions. Following administration of WD-L and CO-L to rats, we detected high level of luteolin-3'-O-β-glucuronide and lower levels of luteolin, luteolin-4'-O-β-glucuronide, and luteolin-7-O-β-glucuronide in plasma from both CO-L and WD-L groups, indicating that the metabolic profile of luteolin was similar for both groups. On top of that, we found a 2.2-fold increase in the plasma area under the curve (AUC) of luteolin-3'-O-β-glucuronide (main luteolin metabolite) in WD-L group (vs. CO-L). Altogether, our results suggested that delivering luteolin by microemulsion system improve its oral bioavailability without affecting its metabolite profile. This evidence thereby provides a solid basis for future application of microemulsion system for optimal delivery of luteolin.

Immunopharmacological Activities of Luteolin in Chronic Diseases

“…Li et al revealed that D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated liposomes provide an effective cancer chemotherapy strategy for model drugs with poor water solubility. Miyashita et al found that delivering luteolin through a microemulsion system can improve its oral bioavailability without affecting its metabolite profile [146,147]. These studies suggest that if the water solubility and bioactivity of luteolin are improved by some procedures, luteolin could be developed as a therapeutic drug to treat various inflammatory and cancerous diseases caused by inflammation or oxidative stress.…”

The Protective Properties of Luteolin: A Comprehensive Review

“…Nonetheless, the bioavailability of luteolin varies depending on the route of administration. For example, luteolin was reported to have an oral bioavailability of approximately 26% after administration, which may have been caused by its poor solubility and high first-pass elimination [18,20]. Remarkably, luteolin demonstrates notable liposolubility, facilitating the absorption through the intestinal mucosa.…”

“…The maximal plasma concentration of luteolin was reached in 30 minutes in pharmacokinetic assays. In situ experiments, the levels of luteolin in jejunum contents were initially 62.3% of the original amount at 5 min., which decreased to 39.7% at 10 min., indicating efficient absorption [18,21]. After oral administration, luteolin is primarily present in the forms of conjugates, with the most prevalent circulating metabolite being luteolin-30-O-β-D-glucuronide.…”

The development of nanocarriers for natural products

“…The tri-ring composition of LUT adopts a twisted planar orientation, where the ortho-dihydroxy configuration on its B ring imparts substantial stability against free radicals, facilitated by hydrogen bonding, indicating LUT's antioxidant potential (F. Sun, Li, et al, 2022). Nonetheless, the solubility parameters of LUT, notably 6 μg/mL at 37 C and pH 6.8 (Miyashita et al, 2022), coupled with its relatively transient half-life of merely 1.8 weeks at 32 C and pH 4 (Bradwell et al, 2018), severely compromise its oral bioavailability, resulting in insufficient accumulation at the targeted sites and inability to achieve the desired medicinal concentration. This necessitates prolonged and repetitive administration, which markedly diminishes patient adherence and clinical effectiveness.…”