Formulation of a Phenol-Rich Extract from Unripe Olives (Olea europaea L.) in Microemulsion to Improve Its Solubility and Intestinal Permeability

Abstract

The beneficial properties of phenolic compounds from Olea europaea L. are well-known. An olive extract (OE) was prepared from unripe olives (Moraiolo cultivar). The study aimed to formulate OE into a microemulsion (ME) in oral dosage form. OE was extracted from olives with EtOH:H2O (80:20) and characterized by HPLC-DAD. ME composition was stated by a solubility and pseudo-ternary diagram. The ME was chemically and physically characterized, and its stability at 4 °C was analyzed for three months. The ability of the formulation to ameliorate the solubility and the intestinal permeability of OE was evaluated by a Parallel Artificial Membrane Permeability Assay (PAMPA) assay and Caco-2 cells. The total phenolic content of the extract was 39% w/w. The main constituent was oleuropein (31.0%), together with ligstroside (3.1%) and verbascoside (2.4%). The ME was prepared using Capryol 90 as the oily phase, and Cremophor EL and Transcutol (2:1) as surfactant and co-surfactant, respectively. ME droplet size was 14.03 ± 1.36 nm, PdI 0.20 ± 0.08, ζ-potential −1.16 ± 0.48. Stability of ME was confirmed for at least three months. The formulation was loaded with 35 mg/mL of OE, increasing the solubility of the extract by about four times. The enhanced permeability of OE was evaluated by PAMPA, as demonstrated by the Pe value (1.44 ± 0.83 × 10−6 cm/s for OE hydroalcoholic solution, 3.74 ± 0.34 × 10−6 cm/s for OE-ME). Caco-2 cell transport studies confirmed the same results: Papp was 16.14 ± 0.05 × 10−6 cm/s for OE solution and 26.99 ± 0.45 × 10−6 cm/s for OE-ME. ME proved to be a suitable formulation for oral delivery.

Recent strategies in nanodelivery systems for natural products: a review

“…The permeability of phenol constituents, evaluated using the parallel artificial membrane permeation assay, was more than 2 times higher compared to that of unformulated olive extract. The transport studies carried out with Caco-2 cells moreover confirmed the increased permeation of the formulated extract (P app of 26.99 ± 0.45 × 10 -6 cm/s versus 16.14 ± 0.05 × 10 -6 cm/s for the unformulated extract), (Cecchi et al 2020).…”

Olive Leaves (<i>Olea europaea</i> L) Extract Loaded Lipid Nanoparticles: Optimization of Processing Parameters by Box-Behnken Statistical Design, <i>in-vitro</i> Characterization, and Evaluation of Anti-oxidant and Anti-microbial Activity

“…Therefore, the inhibition of such a process is considered to be an important therapeutic approach. Various important constituents like Oleuropein (hydroxytyrosol, tyrosol) , verbascoside (also known as acteoside or kusaginin) , ligstroside, apigenin-7-glucoside, diosmetin-7-glucoside, luteolin, catechin, etc were obtained for the leaves of olive and exhibiting anti-oxidant activity as reported previously 10) . Hydroxytyrosol is the principal olive leaves oleuropein that has patent anti-oxidant property 8) .…”

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells

“…The two MEs were prepared following the water titration method [ 32 , 33 ], adding water dropwise to each oily phase/Smix blend. For the first ME (ME-1), the lipophilic phase was obtained by mixing, under constant magnetic stirring at 50 ± 2 °C, Transcutol HP and Tween 20 at a 7:3 ratio with Capmul PG-8/NF, obtaining a final 9:1 Smix/Oil ratio.…”