Polysaccharides-Based Complex Particles’ Protective Role on the Stability and Bioactivity of Immobilized Curcumin
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ABSTRACT:
SUBMITTER: Iurciuc (Tincu) C
PROVIDER: S-EPMC8002829 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Curcumin has been used as a traditional medicine and/or functional food in several cultures because of its health benefits including anticancer properties. However, poor oral bioavailability of curcumin has limited its oral usage as a food supplement and medical food. Here we formulated curcumin pellets using a solid dispersion technique. The pellets had the advantages of reduced particle size, improved water solubility, and particle porosity. This pellet form led to an improvement in curcumin's oral bioavailability. Additionally, we used the C-Map and Library of Integrated Network-Based Cellular Signatures (LINCS) Unified Environment (CLUE) gene expression database to determine the potential biological functions of formulated curcumin. The results indicated that, similar to conventional curcumin, the formulated curcumin acted as an NF-?B pathway inhibitor. Moreover, ConsensusPathDB database analysis was used to predict possible targets and it revealed that both forms of curcumin exhibit similar biological functions, including apoptosis. Biochemical characterization revealed that both the forms indeed induced apoptosis of hepatocellular carcinoma (HCC) cell lines. We concluded that the formulated curcumin increases the oral bioavailability in animals, and, as expected, retains characteristics similar to conventional curcumin at the cellular level. Our screening platform using big data not only confirms that both the forms of curcumin have similar mechanisms but also predicts the novel mechanism of the formulated curcumin.
| S-EPMC6950821 | biostudies-literature
Project description:BACKGROUND: Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. METHODS: In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. RESULTS: Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5±9.8 nm and the drug loading was determined to be 10.32±1.4%. The in vitro release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-?) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. CONCLUSIONS: A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch.
| S-EPMC3497871 | biostudies-other
Project description:Hollow nanoparticles are preferred over solid ones for their high loading capabilities, sustained release and low density. Hollow zein particles are susceptible to aggregation with a slight variation in the ionic strength, pH and temperature of the medium. This study was aimed to fabricate quercetin-loaded hollow zein particles with chitosan and pectin coating to improve their physicochemical stability. Quercetin as a model flavonoid had a loading efficiency and capacity of about 86-94% and 2.22-5.89%, respectively. Infrared and X-ray diffraction investigations revealed the interaction of quercetin with zein and the change in its physical state from crystalline to amorphous upon incorporation in the composite particles. The chitosan/pectin coating improved the stability of quercetin-loaded hollow zein particles against heat treatment, sodium chloride and in a wide range of pH. The complex coating protected quercetin that was encapsulated in hollow zein particles from free radicals in the aqueous medium and enhanced its DPPH radical scavenging ability. The entrapment of quercetin in the particles improved its storage and photochemical stability. The storage stability of entrapped quercetin was enhanced both at 25 and 45 °C in hollow zein particles coated with chitosan and pectin. Therefore, composite hollow zein particles fabricated with a combination of polysaccharides can expand their role in the encapsulation, protection and delivery of bioactive components.
| S-EPMC8470427 | biostudies-literature
Project description:Lassa virus (LASV) is the most prevalent rodent-borne arenavirus circulated in West Africa. With population at risk from Senegal to Nigeria, LASV causes Lassa fever and is responsible for thousands of deaths annually. High genetic diversity of LASV is one of the challenges for vaccine R&D. We developed multivalent virus-like particle vectors (VLPVs) derived from the human Venezuelan equine encephalitis TC-83 IND vaccine (VEEV) as the next generation of alphavirus-based bicistronic RNA replicon particles. The genes encoding VEEV structural proteins were replaced with LASV glycoproteins (GPC) from distantly related clades I and IV with individual 26S promoters. Bicistronic RNA replicons encoding wild-type LASV GPC (GPCwt) and C-terminally deleted, non-cleavable modified glycoprotein (ΔGPfib), were encapsidated into VLPV particles using VEEV capsid and glycoproteins provided in trans. In transduced cells, VLPVs induced simultaneous expression of LASV GPCwt and ΔGPfib from 26S alphavirus promoters. LASV ΔGPfib was predominantly expressed as trimers, accumulated in the endoplasmic reticulum, induced ER stress and apoptosis promoting antigen cross-priming. VLPV vaccines were immunogenic and protective in mice and upregulated CD11c+/CD8+ dendritic cells playing the major role in cross-presentation. Notably, VLPV vaccination resulted in induction of cross-reactive multifunctional T cell responses after stimulation of immune splenocytes with peptide cocktails derived from LASV from clades I-IV. Multivalent RNA replicon-based LASV vaccines can be applicable for first responders, international travelers visiting endemic areas, military and lab personnel.
| S-EPMC5806529 | biostudies-literature
Project description:BackgroundThis study aims to evaluate the inhibitory effect of curcumin (Cur) on the progression of septic acute kidney injury (SAKI), in order to improve the survival rate in this patient population.MethodsAcute kidney injury (AKI) was induced by cecal ligation perforation (CLP) in Sprague-Dawley (SD) rats. Using this AKI animal model, the survival rate of the rats was evaluated at different time points after Cur treatment to explore whether Cur can improve survival in an animal model of AKI. The expression levels of inflammatory factors (NF-κB, TNF-α, and IL-10), organ injury markers [urea nitrogen (UN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, creatine kinase (CK), and lactate dehydrogenase (LDH)], and disease progression markers [neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C (CysC)] were determined using an enzyme-linked immunosorbent assay (ELISA).ResultsThe serum levels of UN, Cr, NF-κB, ALT, AST, amylase, CK, LDH, inflammatory factors TNF-α and IL-10, and markers of early diagnosis of SAKI (NGAL, CysC, KIM-1) were significantly lower in the curcumin group than those in the placebo group (P<0.05). In addition, serum levels of TLR9 and its downstream molecules MyD88, IRF5, and IRF7 in the curcumin group were significantly lower than those in the placebo group (P<0.05). The application of TLR9-specific inhibitors to experimental rats led to similar results as those obtained in the curcumin group, whose detection indexes were significantly lower than those in the placebo treatment group (P<0.05).ConclusionsGiven the excellent performance of Cur in anti-tumor, anti-oxidation, anti-inflammatory, and other clinical trials, it is very likely to be further developed as a potential drug for the clinical treatment of AKI.
| S-EPMC8185681 | biostudies-literature
Project description:Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/ml of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock onto the active sites of CYP17A1, CYP19A1, as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies suggest that curcuminoids may cause inhibition of steroid metabolism, especially at higher dosages. Also, the recent popularity of turmeric powder as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. The molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer.
| S-EPMC6770025 | biostudies-literature
Project description:Contamination of food products by spoilage and pathogenic microorganisms during post process handling is one of the major causes for food spoilage and food borne illnesses. The present green sustainable approach describes the covalent immobilization of papain to LDPE (low density polyethylene), HDPE (high density polyethylene), LLDPE (linear low density polyethylene) and PCL (polycaprolactam) with curcumin as the photocrosslinker. About 50% of curcumin and 82-92% of papain were successfully immobilized on these polymers. After 30 days, the free enzyme retained 87% of its original activity, while the immobilized enzyme retained more than 90% of its activity on these polymers. Papain crosslinked to LLDPE exhibited the best antibiofilm properties against Acinetobacter sp. KC119137.1 and Staphylococcus aureus NCIM 5021 when compared to the other three polymers, because of the highest amount of enzyme immobilized on this surface. Papain acts by damaging the cell membrane. The enzyme is able to reduce the amount of carbohydrate and protein contents in the biofilms formed by these organisms. Meat wrapped with the modified LDPE and stored at 4°C showed 9 log reduction of these organisms at the end of the seventh day when compared to samples wrapped with the bare polymer. This method of crosslinking can be used on polymers with or without functional groups and can be adopted to bind any type of antimicrobial agent.
| S-EPMC4408049 | biostudies-literature
Project description:Isolated anthocyanins have limited colonic bioavailability due to their instability as free forms. Thus, many methods have been fabricated to increase the stability of anthocyanins. Complexation, encapsulation, and co-pigmentation with other pigments, proteins, metal ions, and carbohydrates have been reported to improve the stability and bioavailability of anthocyanins. In this study, anthocyanins extracted from purple potatoes were complexed with four different polysaccharides and their mixture. The anthocyanin-polysaccharide complexes were characterized using a zeta potential analyzer, particle size analyzer, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Complexes were subjected to simulated digestion for assessing the stability of anthocyanins. Furthermore, complexes were subjected to different pH conditions and incubated at high temperatures to monitor color changes. A Caco-2 cell monolayer was used to evaluate the colonic concentrations of anthocyanins. In addition, the bioactivity of complexes was assessed using LPS-treated Caco-2 cell monolayer. Results show that pectin had the best complexation capacity with anthocyanins. The surface morphology of the anthocyanin-pectin complex (APC) was changed after complexation. APC was more resistant to the simulated upper gastrointestinal digestion, and high pH and temperature conditions for a longer duration. Furthermore, APC restored the lipopolysaccharide (LPS)-induced high cell permeability compared to isolated anthocyanins. In conclusion, complexation with pectin increased the stability and colonic bioavailability and the activity of anthocyanins.
| S-EPMC10178255 | biostudies-literature
Project description:Electrostatic interactions play important roles in the formation and stability of viruses and virus-like particles (VLPs) through processes that often involve added, or naturally occurring, multivalent ions. Here, we investigate the electrostatic or osmotic pressure acting on the proteinaceous shell of a generic model of VLPs, comprising a charged outer shell and a metallic nanoparticle core, coated by a charged layer and bathed in an aqueous electrolyte solution. Motivated by the recent studies accentuating the role of multivalent ions for the stability of VLPs, we focus on the effects of multivalent cations and anions in an otherwise monovalent ionic solution. We perform extensive Monte-Carlo simulations based on appropriate Coulombic interactions that consistently take into account the effects of salt screening, the dielectric polarization of the metallic core, and the strong-coupling electrostatics due to multivalent ions. We specifically study the intricate roles these factors play in the electrostatic stability of the model VLPs. It is shown that while the insertion of a metallic nanoparticle by itself can produce negative, inward-directed, pressure on the outer shell, addition of only a small amount of multivalent counterions can robustly engender negative pressures, enhancing the VLP stability across a wide range of values for the system parameters.
| S-EPMC6405863 | biostudies-literature
Project description:The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice.
| S-EPMC5060975 | biostudies-other