Release Of Silymarin Research Articles

Optimizing Production, Characterization, and In Vitro Behavior of Silymarin-Eudragit Electrosprayed Fiber for Anti-Inflammatory Effects: A Chemical Study.

Inflammatory Bowel Disease (IBD) is a chronic condition that affects approximately 1.6 million Americans. While current polyphenols for treating IBD can be expensive and cause unwanted side effects, there is an opportunity regarding a new drug/polymer formulation using silymarin and an electrospray procedure. Silymarin is a naturally occurring polyphenolic flavonoid antioxidant that has shown promising results as a pharmacological agent due to its antioxidant and hepatoprotective characteristics. This study aims to produce a drug-polymer complex named the SILS100-Electrofiber complex, using an electrospray system. The vertical set-up of the electrospray system was optimized at a 1:10 of silymarin and Eudragit® S100 polymer to enhance surface area and microfiber encapsulation. The SILS100-Electrofiber complex was evaluated using drug release kinetics via UV Spectrophotometry, Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). Drug loading, apparent solubility, and antioxidant activity were also evaluated. The study was successful in creating fiber-like encapsulation of the silymarin drug with strand diameters ranging from 5-7 μm, with results showing greater silymarin release in Simulated Intestinal Fluid (SIF) compared to Simulated Gastric Fluid (SGF). Moving forward, this study aims to provide future insight into the formulation of drug-polymer complexes for IBD treatment and targeted drug release using electrospray and microencapsulation.

Designing a Silymarin Nanopercolating System Using CME@ZIF-8: An Approach to Hepatic Injuries.

It is commonly known that silymarin, a phytoconstituent obtained from the Silybum marianum plant, has hepatoprotective and antioxidative properties. However, its low oral bioavailability and poor water solubility negatively impact its therapeutic efficacy. The goal of the present study was to determine the efficiency of the Cordia myxa extract-based synthesized zeolitic imidazole metal-organic framework (CME@ZIF-8 MOF) for increasing silymarin's bioavailability. A coprecipitation technique was used to synthesize the CME@ZIF-8 and polyethylene glycol-coated silymarin-loaded MOFs (PEG-Sily@CME@ZIF-8) and a complete factorial design was used to optimize them. The crystalline size of CME@ZIF-8 was 14.7 nm and the size of PEG-Sily@CME@ZIF-8 was 17.39 nm. The loading percentage of the silymarin drug in CME@ZIF-8 was 33.5%. The optimized formulations were then characterized by ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction, Fourier transform IR spectroscopy, surface morphology, gas chromatography-mass spectrometry, and drug release in an in vitro medium. Additionally, a rat model was used to investigate the optimized formulation's in vivo hepatoprotective effectiveness. The synthesized silymarin-loaded CME@ZIF-8 MOFs were distinct particles with a porous, spongelike shape and a diameter of (size) nm. Furthermore, the designed silymarin-loaded PEG-Sily@CME@ZIF-8 MOF formulation exhibited considerable silymarin release from the synthesized formula in dissolution investigations. The in vivo evaluation studies demonstrated that the prepared PEG-Sily@CME@ZIF-8 MOFs effectively exhibited a hepatoprotective effect in comparison with free silymarin in a CCl4-based induced-hepatotoxicity rat model via ameliorating the normal antioxidant enzyme levels and restoring the cellular abnormalities produced by CCl4 toxication. In combination, biologically produced CME@ZIF-8 may promise to be a viable biologically based nanocarrier that can enhance the loading and release of silymarin medication, which has low solubility in water.

Development and Characterization of Silymarin Phospholipid Complex for Improved Solubility, and Toxicological Evaluation in Experimental Animals

Objectives: The silymarin phytosome (SPY) was developed to improve the solubility and dissolution. The prepared phytosome was evaluated for hemolytic, membrane stabilization activity, and in vivo acute and subchronic toxicity. Materials and Methods: The toxicological evaluation was carried out by assessing its effects on liver, kidney, brain, lungs, heart and spleen in a rat model. In addition to confirmation of formation of phytosome, the physical-chemical characterization was done by FTIR, DSC, PXRD, and 1H NMR. Results: The optimized formulation has higher aqueous solubility of SPY compared to that of pure silymarin. The formulation also exhibited a significantly higher rate and extent of silymarin release in dissolution studies. The percent hemolysis for SPY was significantly less than silymarin. As a result, SPY can be concluded to be non-toxic and biocompatible for in vivo administration. SPY significantly inhibited hypotonic solutioninduced hemolysis in a dose-dependent manner. In acute oral toxicity, no treatment-related death or toxic signs were observed. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination revealed no abnormalities. Conclusion: The study shows that SPY is a promising and viable strategy for improving the delivery of silymarin

Silymarin nanocrystals-laden chondroitin sulphate-based thermoreversible hydrogels; A promising approach for bioavailability enhancement

Hydrogels has gained tremendous interest as a controlled release drug delivery. However, currently it is a big challenge to attain high drug-loading as well as stable and sustained release of hydrophobic drugs. The poor aqueous solubility and low bioavailability of many drugs have driven the need for research in new formulations. This manuscript hypothesized that incorporation of nanocrystals of hydrophobic drug, such as silymarin into thermoreversible hydrogel could be a solution to these problems. Herein, we prepared nanocrystals of silymarin by antisolvent precipitation technique and characterized for morphology, particle size, polydispersity index (PDI) and zeta potential. Moreover, physical cross-linking of hydrogel formulations based on chondroitin sulphate (CS), kappa-Carrageenan (κ-Cr) and Pluronic® F127 was confirmed by Fourier transformed infrared spectroscopy (FT-IR). The hydrogel gelation time and temperature of optimized hydrogel was 14 ± 3.2 s and 34 ± 0.6 °C, respectively. The release data revealed controlled release of silymarin up to 48 h and in-vivo pharmacokinetic profiling was done in rabbits and further analyzed by high-performance liquid chromatography (HPLC). It is believed that the nanocrystals loaded thermoreversible injectable hydrogel system fabricated in this study provides high drug loading as well as controlled and stable release of hydrophobic drug for extended period.

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

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.

Spray-dried nanoemulsion for improved oral delivery of silymarin against hepatic cancer cells

Silymarin recognized for numerous activities, but the use is limited due to poor aqueous solubility, inefficient intestinal permeability, and low-erratic bioavailability. The aim of the current research was formulation of spray-dried nanoemulsion to enhance the solubility of silymarin. The nanoemulsion was prepared by aqueous titration method, spray died and characterized for thermal analysis by diffraction scanning calorimetry, crystallography analysis by x-ray diffraction, surface morphology by scanning electron microscopy. The reconstitution properties were determining for droplet size, polydispersity index and microscopic structure. Optimized nanoemulsion composed of 15% v/v of oil, 33% v/v of Smix and 52% v/v of distilled water demonstrated lowest droplet size (52.4 ± 1.63 nm) and polydispersity index (0.112), optimum viscosity (23.37 ± 2.36 cps), maximum % transmittance (94.55), optimum cloud point (88°C) and cumulative % drug release (98.43%). The microscopic structure of spray-dried nanoemulsion after reconstitution in distilled water revealed spherical shape free from any aggregation. Spray-dried nanoemulsion demonstrated amorphous sate of silymarin after fabrication into solid state. The cumulative % release of silymarin was significantly higher than marketed conventional suspension (Limarin). The developed spray-dried nanoemulsion was robust and stable for a period of 3 months that could be recommended for oral administration of silymarin after further study. Solids are preferred over liquid dosage form; the formulation may offer better patient compliance over liquid nanoemulsion. In addition, the in-vitro cytotoxicity study revealed more cytotoxicity of SD-NE than plain silymarin against HepG2 cell line after 48 h of incubation. Moreover, the HepG2 cellular uptake silymarin was found to be substantially higher from NE when compared to the plain silymarin. Further, silymarin loaded SD-NE could be potential approach against hepatic cancer.
 Keywords: Silymarin, spray-dried nanoemulsion, dextran, phase diagram, solubility, stability

Silymarin-Encapsulated Xanthan Gum-Stabilized Selenium Nanocarriers for Enhanced Activity Against Amyloid Fibril Cytotoxicity.

The accumulation of amyloid-beta at the neuronal sites is a major pathological hallmark involved in the etiology of Alzheimer's disease. To reduce the Aβ-induced neuronal cytotoxicity, selenium nanoparticles and silymarin were fabricated in a single polysaccharide matrix for dual antioxidant and Aβ fibril disaggregation activity. These nanoparticles were further stabilized by an exopolysaccharide xanthan gum. The nanoparticles were fabricated to reduce the amyloid-induced cytotoxicity in SH-SY5Y cells. A three-step method employing redox reaction of sodium selenite and ascorbic acid has been adopted for the synthesis of selenium nanoparticles. Consequently, xanthan gum powder was added to impart stability to the nanocarriers. The nanoparticles exhibited a particle size of 119.2 ± 2.8nm, zeta potential of - 35.4 ± 3.8mV, and % EE of 87.7 ± 2.23. HR-TEM with EDX analysis confirmed the presence of spherical nanoparticles. An in vitro drug release study exhibited 89.33 ± 5.4% release of silymarin from nanocarriers and was able to scavenge 90% free radicals of DPPH reagent. The thioflavin T (ThT) fibrillation kinetics study showed that the nanoparticles elicited maximum disaggregation of Aβ fibrils that was depicted by the quenched fluorescence intensity signal. The cell viability results revealed that the highest neuroprotection activity was observed in the cell group treated with SLY-XG-Se against Aβ 1-42-induced toxicity. The nanoparticles were able to internalize in SH-SY5Y cells. Our findings showed that the nanocarrier elicited anti-aggregation efficacy in neuronal cell lines and mitigated the Aβ-induced cytotoxicity, which represents the prospects of neuroprotection involved in the therapeutics of AD.

Improved Efficacy and Stability of Silymarin Loaded Nanocochleates Over Liposomes for the Treatment of Skin Diseases

Aim: Silymarin, a complex polyphenolic component mixture with anti-oxidant, anti-inflammatory, and membrane-stabilizing property is being investigated in several dermatological conditions. Present research aims to evaluate potential of silymarin loaded nanocochleates and liposomal topical application for treating chronic skin diseases.
 Study Design: Silymarin loaded liposomes and nanocochleates were formulated and optimized using Design Expert software. Different invitro and exvivo tests were performed to compare their performance.
 Place and Duration of Study: The study was conducted in Smt. Kashibai Navale College of Pharmacy, Pune, India, between January 2019 till February 2020.
 Methodology: Liposomes were prepared using ethanol injection method and further treated with calcium chloride to form nanocochleates by trapping method. Design of experiments (32 Factorial Design) was used for optimization of nanocochleates. Cell line studies (HaCaT cell lines) and short term stability studies were performed to compare the efficacy and stability respectively.
 Results: Particle size, entrapment efficiency and drug deposition in Wistar Rat Skin was found to be statistically significant for nanocochleates over liposomes proving superiority of cochleates. Both the carriers sustained release of silymarin for 24h. Antimicrobial efficacy of nanocochleates against E.coli and S.aureus was significant. Inhibition of hyper proliferation of HaCaT cell lines (key mechanism by which most of the antipsoriatic drugs act) demonstrated the superiority of nanocochleates over liposomes.The nanocochleates also displayed better stability compared to liposomes due to decreased entrapment efficacy and leakage of drug.
 Conclusion: Silymarin loaded Nanocochleates could prove as a promising topical drug delivery system for the treatment of chronic skin diseases like psoriasis.

Effect of carrier type and Tween® 80 concentration on the release of silymarin from amorphous solid dispersions

Silymarin is a mixture of flavonolignans obtained from the seeds of milk thistle (Silybum marianum L. Gaertner). Silymarin behaves as a weak acid and is categorised as a class IV drug substance in accordance with biopharmaceutics drug disposition classification system, possessing low solubility, as well as low bioavailability. The scope of this study was to identify possible formulation strategies of silymarin. Then, the main aim was to manufacture silymarin solid dispersions using a solvent evaporation approach and to characterise the physicochemical and drug release properties of the two formulations containing two different porous carriers, namely Avicel® PH-102 and Syloid® XDP 3150, and different concentrations of Tween® 80. Silymarin Log P was determined to be 1.6 (±0.14) negating the possibility of bypassing first pass metabolism via lymphatic transport. Utilising alkaline titration, the apparent pKa of silymarin was found to be similar to that of the silybin pKa (5.68). The crystallinity of raw silymarin was confirmed using powder X-ray diffraction and differential scanning calorimetry, and its thermal degradation was observed at a temperature higher than 220 °C (thermogravimetric analysis). Avicel® PH-102 and Syloid® XDP 3150 were characterised in terms of morphology using scanning electron microscopy, particle size distribution (laser diffraction spectroscopy), pore size distribution and intra-particle porosity using mercury intrusion porosimetry. Solid dispersions were manufactured using an organic solvent method incorporating silymarin, the carrier and optionally Tween® 80. The amorphous state of silymarin in all prepared formulations was confirmed using differential scanning calorimetry and powder X-ray diffraction. Silymarin dissolution kinetics were faster for Syloid® XDP 3150 versus Avicel® PH-102 and explained through carrier properties. The addition of Tween® 80 and increasing the concentration from 0.3 to 1.6% (w/w) significantly increased the drug release kinetics of Avicel® PH-102 formulations but had no effect on Syloid® XDP 3150 formulations. Drug release from prepared formulations was compared with Legalon® 70 using the similarity factor (F2). Syloid® XDP 3150-based formulations showed F2>50%. Tween® 80 had a negligible effect on the silymarin release from Syloid® XDP 3150-based formulations. Interestingly, the ability of Tween® 80 to inhibit gut wall efflux is well known. Thus, the inclusion of this excipient offers an opportunity to modulate the silymarin bioavailability without changing the drug release profile. A six-month stability study (at room temperature and 40% RH) confirmed that solid dispersions were still powder X-ray diffraction and differential scanning calorimetry amorphous. Acetone was used for both silymarin extraction and preparation of solid dispersions. Thus, there is an opportunity to use a single step to both load silymarin and form solid dispersions within a single-step.

The study of silymarin release kinetic in free and hydrogel bound micellar forms: a qualitative and quantitative analysis using RP-HPLC

Silymarin is a safe herbal medicine; however, it has some undesirable properties such as short half-life and poor aqueous solubility. To the best of our knowledge, this study is the first to report utilizing a dual-drug delivery system (DDDS) to enhance the release profile of silymarin from both micelles and hydrogels. In this experimental study, the release profile of micellar silymarin and micelle-hydrogel bounded silymarin during 21 days was examined using Knauer K2600A liquid chromatography. The calibration curve was plotted using the peak-areas of the silymarin at different concentrations. The RP-C18 column allowed a good separation of the components of standard silymarin. LOD and LOQ were 16.5 and 55.02 μg/ml, respectively. The in vitro release profiles of the two compounds showed a rapid release of silymarin, especially in the absence of hydrogel. The cumulative release graph revealed that the hydrogel-bound form has more constant release kinetics than the free micelle form; this means that the hydrogel-bound form may sustain for longer durations. In this study, a dual-drug delivery system based on hydrogel/micelle composites was introduced. The results showed that Puramatrix hydrogel plays an important role in the constant release of silymarin. Furthermore, the RP-HPLC method presented in this study can be used by other researchers to overcome the difficulties associated with the in-vitro separation and quantification of silymarin.

Silymarin encapsulated nanoliquid crystals for improved activity against beta amyloid induced cytotoxicity

Silymarin (SLY) a natural Aβ aggregation inhibitor, antioxidant and act as neuroprotectant. In the present study, we have prepared nano liquid crystals (NLCs) of negatively charged glycerylmonooleate (GMO) loaded with SLY for enhancing activity against Aβ1–42 induced toxicity. SLY-NLCs are characterized for physicochemical parameters such as particle size, zeta potential, and drug-loading. The average particle size, zeta potential and % DL were found ≤200 nm, −22 mV, and 8.73% respectively. The amorphous form and entrapment of SLY in NLC were confirmed using DSC and FTIR analysis. The cubosomal SLY-NLCs shape was characterized by SEM and TEM. The cumulative drug release of SLY was ~76% at pH 7.4 (cerebrospinal fluid) from lyophilized SLY-NLC in 48 h. In order to understand the Aβ1–42 aggregation inhibition due to SLY-NLC ThT (Thioflavin T) kinetic binding assay was also performed. The cell viability assessment of SLY-NLC was performed on SHSY5Y cell line that showed the highest viability in comparison to free SLY treated groups. ROS and apoptosis activity study SLY-NLCs reduced the Aβ1–42 induced free radical with cell death. Cellular uptake study proved enhanced intracellular internalization of FITC tagged NLCs in 24 h. SLY-NLCs can offer great prospects in the field of drug delivery for neuroprotection.

Nanostructured lipid carriers for oral delivery of silymarin: Improving its absorption and in vivo efficacy in type 2 diabetes and metabolic syndrome model

Silymarin (SLM) is a mixture of flavonolignans extracted from the fruit of Silybum marianum L. Gaertn. which has been used for decades as a hepatoprotector. Silymarin has recently been proposed to be beneficial in type 2 diabetic patients. Constituents of SLM are poorly water-soluble and low permeable compounds, with consequently limited oral bioavailability. This study aimed to investigate the possibility of delivery of SLM via nanostructured lipid carriers (NLCs) to overcome these issues and for preparation of an oral dosage form. NLCs were prepared through an emulsion/evaporation/solidifying method. Cetyl palmitate:Lauroglycol 90 was selected as the lipid mixture and Brij S20 as surfactant. NLCs were chemically and physically characterized. Encapsulation efficiency was more than 92%. The storage stability of the NLC suspension was also investigated and the freeze-drying process was taken into consideration. After assessing the stability of the formulation in a simulated gastrointestinal environment, the release of SLM was monitored in different pH conditions. In vitro experiments with artificial membranes (PAMPA) and Caco-2 cells revealed that the NLCs enhanced the permeation of SLM. Active processes are involved in the internalization of NLCs, as evidenced by cellular uptake studies. After preliminary toxicological studies, the formulation was studied in vivo in a streptozotocin (STZ)-induced diabetic mouse model in the presence of metabolic syndrome. The formulation was also compared to an NLC containing stearic acid:Capryol 90, to evaluate the effect of the lipid matrix on the in vivo performance of nanocarriers. Finally, hepatic histopathological analyses were also conducted. Both SLM-loaded NLCs exhibited in vivo a significant down-regulation of blood glucose and triglyceride levels better than free SLM, with a liver-protective effect. Furthermore, both formulations showed a significant anti-hyperalgesic effect on STZ-induced neuropathy.

Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art.

Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from milk thistle (Silybum marianum) seeds, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, although clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.

Formulation and optimization of lyophilized nanosuspension tablets to improve the physicochemical properties and provide immediate release of silymarin

Silymarin (SLM) is a hepatoprotective herbal drug characterized by low aqueous solubility and, consequently, low oral bioavailability. The objective of this study was to enhance the physiochemical properties of SLM, through preparation and optimization of lyophilized nanosuspension tablets (LNTs). LNTs were prepared by sonoprecipitation technique followed by a freeze-drying process using both polyvinyl alcohol (PVA) as stabilizer and binder, and mannitol as cryoprotectant and disintegrating agent. 32 full factorial design (FFD) was applied to study the effect of independent variables at different concentrations of both PVA (X1) and mannitol (X2) on the dependent variables that included mean particle size (Y1), disintegration time (Y2), friability % (Y3) and time required to release 90% of the drug (Y4). Several physicochemical evaluations were implemented on the optimized formula; for instance differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. These analyses demonstrated that the drug was in an amorphous state, stable in nanosize range and displayed no chemical interaction with the polymer. Moreover, the optimized formula had highly porous structure, rapid disintegration, friability with less than 1% and noticeable improvement in saturation solubility and dissolution rate.

Poly(HydroxyButyrate-co-HydroxyValerate) (PHBHV) Nanocarriers for Silymarin Release as Adjuvant Therapy in Colo-rectal Cancer.

The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the in vitro culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, in vivo-like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.

SIMULTANEOUS DIAGNOSIS AND DRUG DELIVERY BY SILYMARIN-LOADED MAGNETIC NANOPARTICLES

Objective(s): The aim of this work was to prepare and characterize magnetic nanoparticles (MNPs) as theranostic system to act simultaneously as drug carrier and MRI contrast agent. Chitosan-coated MNPs (CMNPs) were prepared and loaded with silymarin. Silymarin-loaded CMNPs were characterized with various techniques and their potential as MRI contrast agent was also evaluated. Materials and Methods: The chitosan-coated MNPs were prepared by coprecipitation method and were loaded with silymarin. The synthesized nanoparticles were characterized by various techniques including SEM, TEM, X ray diffraction (XRD), FTIR and vibrating sample magnetometer (VSM). In vitro drug release of silymarin was evaluated at 37 UC at pH 5.3 and 7.4. Then, their proton relaxivity was evaluated to study the potential of CMNPs as MRI contrast agent in terms of r 1 and r 2 . Results: Silymarin-loaded CMNPs were successfully prepared and characterized by FTIR and XRD techniques. VSM analysis revealed superparamagnetic properties of CMNPs. The release study showed that the maximum drug release accessible for CMNPs in pH=5.3 was higher than pH=7.4. Finally, the r 2 /r 1 value of CMNPs was found to be close to 20 indicating that CMNPs has a strong efficiency as T 2 contrast agents for MRI imaging. Conclusion: The findings demonstrated the potential of CMNPs as efficient MRI contrast agent as well as silymarin drug delivery.

Involvement of phospholipase A2 in the release of silymarin to the culture medium of Silybum marianum cell suspensions

In suspension cell cultures of Silybum marianum, methyl jasmonate (MJ) stimulated the accumulation and release of silymarin (Sm) to the culture medium. This study shows that phospholipase A2 (PLA2) plays a role in the release of Sm in elicited cultures. PLA2 activity increased in cell suspensions treated with MJ. Addition of aristolochic acid (AA) or bromoenol lactone (BEL) compounds that inhibit PLA2 activity impeded silymarin release. The addition of linoleic or linolenic acid reversed the inhibitory action of AA. Fatty acids (FAs) stimulated Sm release when added alone to control cultures. By contrast, oleic acid and saturated FA were ineffective in emulating MJ action.

Cellulose Acetate Electrospun Fiber Mats for Controlled Release of Silymarin

In this research, the silymarin-loaded electrospun cellulose acetate (CA) fibers were prepared which containing silymarin in various amounts (i.e., 2.5-20 wt.% based on the weight of CA powder). Incorporation of silymarin in the neat CA solution did not affect the morphology of the resulting fibers, as both the neat and the silymarin-loaded CA fibers were smooth. The average diameters of silymarin-loaded CA fiber ranged between 550-900 nm. No presence of the silymarin aggregates of any kind was observed on the surfaces of these fibers, suggesting that the silymarin was encapsulated well within the fibers. These results were confirmed by lowering the glass transition temperature and the melting temperature of the silymarin-loaded electrospun CA fibers which is determined by DSC technique. The release characteristic of silymarin from the silymarin-loaded CA fiber mats was investigated by the total immersion in the solution of 1/1 phosphate buffer/methanol medium pH 7.4 at 37 degrees C. The silymarin release from the silymarin-loaded electrospun CA fiber mat is monotonously increased to reach the maximum value at 480 min. The maximum amount of silymarin released from these materials increases with the increasing of initial silymarin loading in the spinning CA solutions. Since no aggregation of silymarin was found on the surface of the silymarin-loaded fibers, the release of the silymarin from fiber mats was mainly by the diffusion.

Silymarin Glyceryl Monooleate/Poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability

Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

Micellar Solubilization and In Vitro Release of Silymarin in the self‐Aggregates of an Amphiphilic Derivative of Chitosan

AbstractSummary: The amphiphilic derivatives of chitosan, (2‐hydroxyl‐3‐butoxyl)‐propylcarboxymethyl‐chitosan (HBP‐CMCHS), can form micelles with the inner core of hydrophobic segments and the outer shell of hydrophilic segments. The typical poor water‐soluble drug silymarin was solubilized in the HBP‐CMCHS micellar by physical entrapped method. Results showed that the solubilizing capacity was enhanced by increasing the concentration of HBP‐CMCHS with the same dosage of silymarin. Silymarin‐loaded micellar system of HBP‐CMCHS was characterized by TEM and DLS. TEM photograph revealed that the micelles were spherical and silymarin was solubilized in the cores of the spherical polymeric micelles. DLS showed that after solubilization the size of the micelles became bigger. In vitro tests showed that silymarin was slowly released from micellar solution and the release lasted up to 40 h by means of the dialysis method.