Silymarin loaded liposomes for hepatic targeting: In vitro evaluation and HepG2 drug uptake (original) (raw)
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Preparation and Biological Evaluation of Silybin Liposomes for the Treatment of Liver Disorders
Journal of Pharmaceutical Research International, 2021
Aim: The aim of the present study was to develop silybin liposome by incorporating phosphatidyl choline & cholesterol so as to increase its oral bioavailability and liver targeted enhanced hepatoprotection. Methodology: Thin film hydration technique was used for the development of liposomes by using phosphatidyl choline, cholesterol and drug. Liposomes were evaluated for vesicle size, zeta potential, PDI, encapsulation efficiency, surface morphology and in vitro drug release study. Further the optimized formulation was evaluated for APAP-induced alterations in liver and kidney function tests in rats and histopathological studies. Results: The results were promising with a sustained drug release of 80% within 20hrs, optimized vesicle size of 276nm and 89% encapsulation efficiency. The animal studies demonstrated superior hepatoprotective effect compared to silybin solution. Conclusion: The silybin liposomes showed better in-vitro release & in-vivo hepatoprotection along with better a...
Pharmacological Reports, 2014
Background: Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomalliposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. Methods: The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. Results: The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Conclusions: Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.
Biological and Pharmaceutical Bulletin, 2002
Liposomes formed by a bilayer membrane of phospholipid are useful drug carriers that can contain or entrap various drugs. They are biodegradable and have low toxicity because they consist of natural components of biomembranes such as phospholipids and cholesterol. As they can be modified with various kinds of ligand such as immunoglobulin, 1) protein 2) or sugar residues, 3,4) they can be used for drug targeting to specific sites and enhance the therapeutic effects by increasing drug association. We previously reported that drugs entrapped in liposomes modified with soybean-derived sterylglucoside (SG, SG-liposomes) accumulated in the liver, especially in hepatocytes, when administered to mice. 5,6) Recognition of glucose moieties in liver cells was reported in previous studies, in which glucosylated albumin with a positively charged spacer in proximity to the sugar residue showed better effective uptake by isolated rat hepatocytes 7) and hepatocytes in mice 8) via asialoglycoprotein receptor (ASGP-R), which recognizes galactose residues. We also reported that both SG and b-sitosterol glucoside (Sit-G), a major component of SG, are effective penetration enhancers of drugs across mucosal membranes and the enhancement effect of Sit-G is higher than that of SG. 9,10) Bile salt and glycyrrhizin are known to act as penetration enhancers in the intestinal, 11) nasal 12,13) and transdermal 14) absorption of drugs, and also as ligands for drug delivery to the liver by their specific affinities to hepatocytes. 15,16) Thus the penetration-enhancing effect of free SG or Sit-G on hepatocytes cannot be neglected, because they might be released by the degradation of SG-liposomes in the blood circulation or by Kupffer cells after i.v. injection. Therefore, we examined whether the accumulation of drug entrapped in SG-liposomes in the liver can be interpreted as indicating that SG is a liver-targeting ligand due to recognition by ASGP-R and Sit-G works as a penetration enhancer close to the hepatocyte.
Review Article LIPOSOME AS A POTENTIAL DRUG DELIVERY SYSTEM: A REVIEW
Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles ("first-generation liposomes") to "second-generation liposomes", in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposomeencapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.
LIPOSOME AS A POTENTIAL DRUG DELIVERY SYSTEM: A REVIEW
Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles ("first-generation liposomes") to "second-generation liposomes", in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposome-encapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.
Formulation, Characterization, and In Vitro Evaluation of Silymarin-Loaded Lipid Microspheres
Drug Delivery, 2004
The objective of our study was to incorporate and evaluate Silymarin, a chemically defined natural hepatoprotective agent, in lipid microstructured systems. Various constituents of lipid microspheres-namely, internal oily core; surfactant such as soyabean lecithin; and cosurfactants such as span 20, tween 20, tween 80, and propylene glycol-were tried in different concentrations to optimize the final formulation characteristics such as globule size range, structural integrity, sustainability, and percent drugholding capacity. The final formulation (formulation A) was characterized with respect to size and morphology using transmission electron microscopy and laser diffraction technique. The enhanced mean percent release of 56.70 ± 2.03% was observed in 36 hr from silymarin-loaded lipid microspheres (formulation A), as compared to 18.67 ± 0.192% with silymarin solution (formulation B). Thus, a stable delivery system having synergistic hepatoprotective effect of silymarin and soyabean lecithin could successively be produced for passive targeting to the liver.
Journal of Controlled Release, 2001
We investigated the interaction of liposomes surface-modified with soybean-derived sterylglucoside (SG) (SG-liposomes) with HepG2 cells in the point of involvement of asialoglycoprotein receptor (ASGP-R) mediated endocytosis and examined the efficiency of SG-liposomes as drug carriers using 1,19-dioctadecyl-3,3,39,39-tetramethylindocarbocyanine perchlorate (DiI) as a maker of liposome, carboxylated polystyrene microspheres (Fluoresbrite) as a model drug not taken up in cells and doxorubicin (DXR). SG-liposomes were composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Ch) and SG (DPPC / Ch / SG56:3:1, molar ratio) and DiI, Fluoresbrite and DXR were entrapped in SG-liposomes, respectively. Each SG-liposome was incubated with HepG2 cells at 4 or 378C, and co-incubated with asialofetuin (AF) as a competitor of ASGP-R. The association of DiI, Fluoresbrite or DXR entrapped in SG-liposomes with HepG2 cells at 378C was significantly higher than that in liposomes containing no SG. That of DiI and Fluoresbrite was reduced significantly by the incubation with AF, but that of DXR was not affected. These findings suggest that Fluoresbrite behaves like the lipid component of SG-liposomes, but DXR in SG-liposomes does not behave similar to the lipid component of SG-liposomes, thus, its drug behavior released from liposomes may be due to its physicochemical properties. SG-liposomes are potentially useful drug carriers to the liver, because the glucose residue may work as a kind of ligand for ASGP-R.
Liposomes as Drug Carrier for Novel Drug Delivery System
2018
A liposome is a tiny bubble (vesicle), made out ofthe same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. An artificial microscopic vesicle consisting of an aqueous core enclosed in one or more phospholipid layers, used to convey vaccines, drugs, enzymes, or other substances to target cells or organs. Liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to 'second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This review discusses the classification, formulation, characterization and potential applications of liposomes in drug delivery.
Open Journal of Pharmacology and Pharmacotherapeutics, 2018
Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were fi rst described in the mid-60s. Nowadays, they are a very useful reproduction, reagent, and device in various scientifi c disciplines, including medicine, chemistry, biochemistry, colloid science, biology, physics, biophysics, mathematics and theoretical. After the initial discoveries liposomes have made their way to the market. Among numerous brilliant new drug delivery systems developed, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to 'second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modifi ed surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper mini review summarizes exclusively Nano-lipids, its applications in medicine scalable techniques in treating dreadful diseases cancer, AIDS, paralysis etcand focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.
NIOSOMES AS A NOVEL PHARMACEUTICAL FORMULATION ENCAPSULATING THE HEPATOPROTECTIVE DRUG SILYMARIN
Silymarin is a purified extract isolated from seeds of the milk thistle Silybum marianum. It has been used for more than 2000 years to treat liver and gallbladder disorders. Based on the poor bioavailability of silymarin and on the advantages of niosomes, the objective of this research is to develop a silymarin niosomal preparation with enhanced activity and limited side effects. Silymarin loaded niosomes were prepared using different non-ionic surfactants (NIS), cholesterol (Ch) and different charge inducing agents (CIA) in molar ratios (1:1:0.1) and (2:1:0.25). The effect of components molar ratio and effect of surface charges on the percentage drug encapsulated were investigated. Characterization of prepared niosomes was performed via transmission electron microscopy (TEM), differential scanning calorimetry (DSC), particle size analysis and also investigation of the in-vitro release profiles. Selected silymarin niosomal formulations were evaluated for their hepatoprtective activity against carbon tetrachloride (CCl4) induced oxidative stress in albino rats. Biochemical parameters like serum glutamate oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (SALP) were used to measure the degree of liver protection. Silymarin niosomal formulations produced a significant decrease in both transaminase levels as well as in SALP level in comparison with administered silymarin suspension. This improvement was also proven histopathologically.