Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Abstract

Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.

Enhancement of Silymarin Anti-fibrotic Effects by Complexation With Hydroxypropyl (HPBCD) and Randomly Methylated (RAMEB) β-Cyclodextrins in a Mouse Model of Liver Fibrosis

“…Some pharmaceutical formulations, such as nanostructured lipid carriers (NLCs) ( Jia et al, 2010 ), liposomes ( El-Samaligy et al, 2006 ; Elmowafy et al, 2013 ; Kumar et al, 2014 ), nanoemulsions ( Parveen et al, 2011 ), solid lipid nanoparticles ( Cengiz et al, 2015 ), gold nanoparticles ( Kabir et al, 2014 ), alginate-poly (lactic-co-glycolic acid) nano/micro hydrogel matrices ( El-Sherbiny et al, 2011 ), self-nanoemulsifying drug delivery systems ( Iosio et al, 2011 ; Chen et al, 2015 ), have been used to increase the aqueous solubility of silymarin. Among these, gold nanoparticles were designed to ameliorate liver fibrosis, and Au-silymarin conjugates were administered for up to 14 weeks without any noticeable side effects in the morphology of heart, kidney and lungs of the animals ( Kabir et al, 2014 ).…”

Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: an attempt to enhance its oral bioavailability

“…In addition, silibinin has been reported to effectively treat lung cancer 17. Self-nanoemulsifying drug delivery systems (SNDDS) for silymarin have recently been developed to improve its therapeutic performance 18. Liu et al19 have found silibinin NPs to have strong antiviral effect against hepatitis C virus (HCV) infections.…”

“… 17 Self-nanoemulsifying drug delivery systems (SNDDS) for silymarin have recently been developed to improve its therapeutic performance. 18 Liu et al 19 have found silibinin NPs to have strong antiviral effect against hepatitis C virus (HCV) infections. The role of silibinin as a potential candidate to treat breast cancer has been studied by Sun et al 20 Phospholipid carriers have become an attractive tool to address the issue of poorly water-soluble active pharmaceutical ingredients.…”

A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol

“…However, the S-SNEDDS showed a double peak at 0.25 and 1–2 h. It has been reported that lipid formulations, such as microemulsions (Larsen et al., 2013 ; Xiao et al., 2013 ), nanocrystal self-stabilized emulsions (Yi et al., 2016 ), and self-emulsifying pellets (Iosio et al., 2011 ) show the double peak plasma phenomenon due to enterohepatic circulation, efflux transporters and phase II conjugation, and lymphatic transport, respectively. Thus, in our study, such a double peak might be contributed by enterohepatic circulation and the complex absorption of PLAG involved in transport and metabolism (Chen et al., 2015 ). The pharmacokinetic parameters are summarized in Table 1 .…”