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Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin.

ABSTRACT: Silymarin, a phyto-constituent derived from the plant Silybum marianum, has been widely acknowledged for its hepatoprotective activities. Nevertheless, its clinical utility is adversely hampered by its poor water-solubility and its limited oral bioavailability. The aim of this study was to investigate the efficacy of phospholipid-based phytosomes for enhancing the oral bioavailability of silymarin. The phytosomes were prepared using the solvent evaporation technique and were optimized using a full factorial design. The optimized silymarin phytosomal formulation was then characterized for particle size, surface morphology, aqueous solubility, and in vitro drug release. Furthermore, in vivo antioxidant activity, hepatoprotective activity and oral bioavailability of the optimized formula were investigated in a rat model. The prepared silymarin phytosomes were discrete particles with a porous, nearly smooth surface and were 218.4 ± 2.54 nm in diameter. In addition, the optimized silymarin phytosomal formulation showed a significant improvement in aqueous solubility (~360 µg/mL) compared to pure silymarin and manifested a higher rate and extent of silymarin release from the optimized formula in dissolution studies. The in vivo assessment studies revealed that the optimized silymarin phytosomal formulation efficiently exerted a hepatoprotective effect in a CCl₄-induced hepatotoxicity rat model via restoring the normal levels of antioxidant enzymes and ameliorating cellular abnormalities caused by CCl₄-intoxication. Most notably, as compared to pure silymarin, the optimized silymarin phytosomal formulation significantly improved silymarin oral bioavailability, as indicated by a 6-fold increase in the systemic bioavailability. Collectively, phytosomes might represent a plausible phospholipid-based nanocarrier for improving the oral bioavailability of phyto-constituents with poor aqueous solubility.

SUBMITTER: Shriram RG

PROVIDER: S-EPMC9318442 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

Project description:AimCanagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ.MethodsSolid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols.ResultsThe optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in Cmax and 2.73 and 1.98 fold in AUC 0-24h, as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis.ConclusionThe current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation. Graphical abstract Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

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Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin.

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