Formulation of Phytosomes with Extracts of Ginger Rhizomes and Rosehips with Improved Bioavailability, Antioxidant and Anti-Inflammatory Effects In Vivo

Abstract

The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. 31P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds.

Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders

“…Different solvents have been used for phyto-phospholipid complex formulation. Aprotic solvents, such as methylene chloride, chloroform, tetrahydrofuran, dimethylsulfoxide, ethyl acetate or acetone have been used to prepare phytosomes, but they have been largely replaced by protic solvents like ethanol, because it is a food grade solvent, leaves less residues and causes minimal damage [37,38]. Regarding the stoichiometric ratio of bioactive compounds and phospholipids, the phyto-phospholipid complexes are employed by reacting the ingredients in a molar ratio ranging from 0.5 to 2.0 [39].…”

“…The resulting dry film can be sieved and stored in a desiccator or can be hydrated with the optimum volume of water, followed by controlled sonication in order to obtain a certain size for the phytosome particles. Then, the phyto-phospholipid complexes can be freeze-dried for long-term preservation, and later formulated in capsules (Figure 3) [38,41,42]. phytosome particles.…”

“…phytosome particles. Then, the phyto-phospholipid complexes can be freeze-dried for long-term preservation, and later formulated in capsules (Figure 3) [38,41,42]. The anti-solvent precipitation technique is the second most used method for the preparation of phytosomes.…”

“…The size and morphology of particles are important indicators of the phytosomes' quality. Different techniques can be used for phytosome size characterization, such as dynamic light scattering (DLS) [18,38,[45][46][47], transmission electron microscopy (TEM) [18,38,[47][48][49][50], scanning electron microscopy (SEM) [18,[47][48][49]51,52], atomic force microscopy (AFM) [53] and size-exclusion chromatography (SEC) [54]. The measurement of size distribution and polydispersity of phytosomes gives information about their physical stability; it can be evaluated by DLS, an easy, very fast and precise method [18,38,[45][46][47].…”

“…Different techniques can be used for phytosome size characterization, such as dynamic light scattering (DLS) [18,38,[45][46][47], transmission electron microscopy (TEM) [18,38,[47][48][49][50], scanning electron microscopy (SEM) [18,[47][48][49]51,52], atomic force microscopy (AFM) [53] and size-exclusion chromatography (SEC) [54]. The measurement of size distribution and polydispersity of phytosomes gives information about their physical stability; it can be evaluated by DLS, an easy, very fast and precise method [18,38,[45][46][47]. Zeta potential represents the complete charge generated by medium, defines the surface charge of phytosomes in emulsions and reflects the stability of the phytosomes in the medium.…”