Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic disease that causes excessive hepatic lipid accumulation. Reducing hepatic lipid deposition is a key issue in treatment and inhibition of NAFLD evolution. Silymarin is a potent hepatoprotective agent; however, it has low oral bioavailability due to its poor aqueous solubility and low membrane permeability. Unfortunately, few studies have addressed the development of convenient oral nanocarriers that can efficiently deliver silymarin to the liver and enhance its lipid-lowering effect. We designed silymarin-loaded lipid polymer hybrid nanoparticles containing chitosan (CS-LPNs) to improve silymarin bioavailability and evaluated their lipid-lowering effect in adiponutrin/patatin-like phospholipase-3 I148M transgenic mice, an NAFLD model.ResultsCompared to chitosan-free nanoparticles, CS-LPNs showed 1.92-fold higher uptake by fatty liver cells. Additionally, CS-LPNs significantly reduced TG levels in fatty liver cells in an in vitro lipid deposition assay, suggesting their potential lipid-lowering effects. The oral bioavailability of silymarin from CS-LPNs was 14.38-fold higher than that from suspensions in rats. Moreover, compared with chitosan-free nanoparticles, CS-LPNs effectively reduced blood lipid levels (TG), improved liver function (AST and ALT), and reduced lipid accumulation in the livers of mice in vivo. Reduced macrovesicular steatosis in pathological tissue after CS-LPN treatment indicated their protective effect against liver steatosis in NAFLD.ConclusionsCS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model. These findings suggest that CS-LPNs may be a promising oral nanocarrier for NAFLD therapeutics.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0391-9) contains supplementary material, which is available to authorized users.

Preparation a core‐shell lipid/polymer nanoparticle containing Isotretinoin drug with pH sensitive property: A response surface methodology study

“…In another study, silymarin‐loaded lipid polymer hybrid nanoparticles containing chitosan was prepared to improve silymarin bioavailability by oral delivery. The findings suggest that chitosan polymer (CS)‐lipid polymer NPs may be a promising oral nanocarrier 20 …”

“…The findings suggest that chitosan polymer (CS)-lipid polymer NPs may be a promising oral nanocarrier. 20 To the best of our knowledge, the loading of Isotretinoin into polymer-based nanoparticles has not been studied. Here, lipid coated polymeric nanoparticles have been applied for oral delivery of Isotretinoin drug.…”

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

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The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…It is highly available as a natural cationic aminopolysaccharide polymer of marine origin, prepared from crustaceans’ shells, and classified as generally recognized as safe (GRAS) by USFDA [ 95 ]; thus, it owns ideal biological properties. It also exhibits hepato-protective effect [ 96 ], regulatory impact of carbohydrates and lipid metabolism, ameliorating insulin resistance, and decreasing the prevalence of MAFLD [ 97 , 98 ], along with the decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels in the in vivo studies [ 99 ]. In addition, it owns a lipid-lowering capacity, through promoting weight loss, lowering LDL, and boosting high-density lipoprotein (HDL), with a suggested mechanism linked to the polymer’s positive charge, which attracts the negatively charged fatty acids and bile acids binding them to the indigestible chitosan fiber [ 100 ].…”

“…Both formulations offered a burst release drug delivery, and the relative bioavailability study on healthy male Wistar rats with an oral dose of 20 mg/kg showed that silymarin-HLPNP with PLGA and chitosan offered a bioavailability of 1.23-fold and 14.38-fold higher than that of silymarin-HLPNP with PLGA alone, and pure silymarin suspension, respectively. The hepatoprotective and antihyperlipidemic effects of silymarin-HLPNP with PLGA and chitosan in MAFLD conditions were suggested through reducing the AST and ALT serum levels significantly in PNPLA3 I148M transgenic male and female mice with notably less macrovesicular steatosis compared to the group treated with pure silymarin suspension [ 97 ].…”