Lipid nanoparticulate drug delivery system for the treatment of hepatic fibrosis (original) (raw)
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Nanotechnology applications for the therapy of liver fibrosis
World journal of gastroenterology : WJG, 2014
Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and, in the more advanced stages, for the limited available curative treatment options. In fact, when lesions of different etiologies chronically affect the liver, triggering the fibrogenesis mechanisms, damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications, expensive treatments and death in end-stage liver disease. Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis, the drugs used in liver fibrosis treatment still have a limited therapeutic effect. Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected. Hepatic stellate cells play a critical role in liver fibrogenesis , thus they are the targ...
Modified Lipid Nanocapsules for Targeted Tanshinone IIA Delivery in Liver Fibrosis
International Journal of Nanomedicine, 2021
Introduction: Liver fibrosis represents a serious global disease with no approved treatment. Tanshinone IIA (TSIIA) is a phytomedicine with documented activity in treating many hepatic disorders. TSIIA has been reported to have potent anti-inflammatory and antioxidant properties. It can also induce apoptosis for activated hepatic stellate cells, and is thereby considered as a promising herbal remedy for treating fibrotic liver. However, its poor aqueous solubility, short half-life, exposure to the first-pass effect, and low concentration reaching targeted cells constitute the major barriers hindering its effective therapeutic potential. Therefore, this work aimed at enhancing TSIIA systemic bioavailability together with achieving active targeting potential to fibrotic liver via its incorporation into novel modified lipid nanocapsules (LNCs). Methods: Blank and TSIIA-loaded LNCs modified with either hyaluronate sodium or phosphatidyl serine were successfully prepared, optimized, and characterized both in vitro and in vivo. Results: The developed LNCs showed good colloidal properties (size ≤100 nm and PDI ≤0.2), high drug-entrapment efficiency (>97%) with sustained-release profile for 24 hours, high storage stability up to 6 months, and good in vitro serum stability. After a single intraperitoneal injection, the administered LNCs exhibited a 2.4-fold significant increase in AUC 0-∞ compared with the TSIIA suspension (p≤0.01). Biodistribution-study results proved the liver-targeting ability of the prepared modified LNCs, with a significant ~1.5-fold increase in hepatic accumulation compared with the unmodified formulation (p≤0.05). Moreover, the modified formulations had an improved antifibrotic effect compared with both unmodified LNCs and TSIIA suspension, as evidenced by the results of biochemical and histopathological evaluation. Conclusion: The modified TSIIA-LNCs could be regarded as promising novel targeted nanomedicines for effective management of liver fibrosis.
Inorganic Nanomaterials as Highly Efficient Inhibitors of Cellular Hepatic Fibrosis
ACS Applied Materials & Interfaces, 2018
Chronic liver dysfunction usually begins with hepatic fibrosis. To date, there are still no effective anti-fibrotic drugs approved for clinical use in humans. In the current work, titanium dioxide (TiO) nanoparticles (NPs) and silicon dioxide (SiO 2) NPs are used as active inhibitors with intrinsic chemico-physico properties to block fibrosis and the associated phenotypes through acting on hepatic stellate cells (HSCs, the liver machinery for depositing scar tissues seen in fibrosis). Using LX-2 cells as the HSC model, internalized nanomaterials are found to suppress classical outcomes of cellular fibrosis, e.g., inhibit the expression of collagen I (Col-I) and alpha smooth muscle actin (α-SMA), initiated by transforming growth factor β (TGF-β)-activated HSCs in both a concentration-dependent and a time-dependent manner. Biochemically, these nanomaterials could also facilitate the proteolytic breakdown of collagen by up-regulation of matrix metalloproteinases (MMPs) and down-regulation of tissue inhibitors of matrix metalloproteinases (TIMPs). Furthermore, through regulating epithelial-mesenchymal transition (EMT) genes (e.g., E-cadherin (E-Cad) and N-cadherin (N-Cad)), the adhesion and migration profiles of TGF-β-activated LX-2 cells treated with nanomaterials were further inhibited, reverting them to a more quiescent state. Thus, the collective evidences pave the new way that nanomaterials can be used as potential therapeutic inhibitors for the treatment of in vivo fibrosis.
Journal of Nanobiotechnology, 2022
Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive n...
Innovative Nanotechnological Formulations to Reach the Hepatic Stellate Cell
Current Tissue Microenvironment Reports
Purpose of Review Treatment of liver fibrosis benefits from hepatic stellate cell (HSC)-specific delivery. Since the description of first carrier to HSC, many developments have taken place in this area. The purpose is to give an overview of the different carriers and homing moieties that are available for HSC targeting and illustrate the opportunities and hurdles they provide. Recent Findings There is a growing number of homing devices to deliver drugs to HSC, and options to deliver siRNA to HSC have emerged. Other developments include controlling corona formation, development of linker technology, and design of theranostic approaches. We are on the eve of reaching the clinic with innovative HSC-specific compounds. Summary An overview of different core molecules is presented together with an overview of targeting strategies toward different receptors on HSC, providing a versatile toolbox. Many therapeutics, ranging from small chemical entities and proteins to RNA- or DNA-modulating ...
Pharmaceutical Research, 2020
Purpose Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression. Methods GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored. Results Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats' livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities,
Cirrhosis can arise in consequence of an exogenous/ toxic, infectious, toxic/allergic, immunopathological/ autoimmune, or vascular process or an inborn error of metabolism. The commonest causes of cirrhosis in Germany are alcoholic and non-alcoholic fatty liver disease and viral hepatitis (B or C). Among these causes, the most common of all is alcoholic fatty liver disease, which caused 8619 deaths in Germany (8.9 deaths per 100 000 population) in 2009 and thus ranks among the country's top 20 causes of death. Cirrhosis is rising in importance as a public health problem: the number of deaths from cirrhosis per 100 000 population doubled from 5 in 1980 to 9.9 in 2005. Autopsy studies have revealed fatty liver disease in 70% of overweight persons and in 35% of persons of normal weight. They have also revealed cirrhosis in 18.5% of overweight diabetics. 0.5% of the German population are chronically infected with the hepatitis B virus, and 0.5% with the hepatitis C virus. The aim of this study is to develop, characterize silymarin loaded Solid lipid nanoparticles for the treatment of psoriasis.
Liver diseases are the second most predominant diseases next to diabetes. Treatment of most of the liver diseases involves liver transplantation, which is not feasible due to lack of sufficient donors. Most of the drugs prescribed are random and doesn't involve proper action in the patient. Hence targeted delivery of the drug is the most viable and affordable solution for treating liver diseases. Despite many available carriers like viral vectors, metallic vectors etc, liposomes are the most suitable drug carrier molecules and they are more advantageous than other materials. Targeted delivery experiments involve much tedious experimental procedures and complex biological pathway study. Developing and analysing these nano scale compounds are also much difficult and hence for the ease of work, tools of Bioinformatics are used to analyse and interpret the results. Hence in-Silico analysis are commonly used for analysing their pathway before carrying out the in-Vitro and in-Vivo experiments. This review article emphasis on the various procedures and software used in targeted delivery experiments.
Hepatology, 2015
Fibrosis accompanies the wound‐healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I. Fibrosis often progresses to cirrhosis. Here we present in vivo evidence of an up to 90% suppression of procollagen α1(I) expression, a reduction of septa formation, and a 40%‐60% decrease of collagen deposition in mice with progressive and advanced liver fibrosis that received cationic lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene. After intravenous injection, up to 90% of lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene were retained in the liver of fibrotic mice and accumulated in nonparenchymal more than parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis. Conclusion: Our lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene specifically reduce tot...
Drug delivery, 2018
Hepatic macrophages have been considered as a therapeutic target for liver fibrosis treatment, and phosphatidylserine (PS)-containing nanoparticles are commonly used to mimic apoptotic cells that can specifically regulate macrophage functions, resulting in anti-inflammatory effects. This study was designed to test the efficacy of PS-modified nanostructured lipid carriers (mNLCs) containing curcumin (Cur) (Cur-mNLCs) in the treatment of liver fibrosis in a rat model. Carbon tetrachloride-induced liver fibrosis in rats was used as an experimental model, and the severity of the disease was examined by both biochemical and histological methods. Here, we showed that mNLCs were spherical nanoparticles with decreased negative zeta potentials due to PS decoration, and significantly increased both mean residence time and area under the curve of Cur. In the rats with liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting to the diseased liver, which was evidenced by thei...