Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection.

RNA therapy represents a great way to precisely regulate cellular processes by modulating the gene expression. Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self-regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed. To demonstrate the efficacy of this delivery system, we used it to treat human cytomegalovirus (HCMV) infection in a humanized mouse model. In this study, we use small interfering RNA (siRNA) and small complementary RNA (scRNA) to inhibit the expressions of two HCMV genes, IE1 and IE2. The auto-regulated nanocarrier polywraplex with core-shell structure was designed to condense and package these RNAs for delivering. To allow these particles recognize the HCMV-infected cells, a ligand was coupled on the surface of nanoparticle, which would specifically target the HCMV-encoded CX3 CL1 chemokine receptor presented in the HCMV-infected cells. The results demonstrated that the polywraplex conjugated with the target molecule CX3 CL1 effectively and specifically delivered the siRNA/scRNA to HCMV infected cells and inhibited virus growth in vitro and in vivo.

1,2,4-Triazole hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has developed numerous mechanisms of virulence and strategies to evade the human immune system, and it can be transmitted between humans, animals, and the environment. Thus, MRSA is an important cause of morbidity and mortality in both hospitals and in the community, creating an urgent demand for the development of novel anti-MRSA candidates. The 1,2,4-triazole nucleus is a bioisostere of amide, ester, and carboxylic acid, and the 1,2,4-triazole ring is found in many compounds with diverse biological effects. 1,2,4-Triazole derivatives could exert their antibacterial activity through inhibition of efflux pumps, filamentous temperature-sensitive protein Z, penicillin-binding protein, DNA gyrase, and topoisomerase IV, and they play an important role in the discovery of novel antibacterial agents. Among them, 1,2,4-triazole hybrids, which have the potential to exert dual/multiple mechanisms of action, possess a promising broad-spectrum antibacterial activity against a panel of clinically important drug-resistant pathogens including MRSA. This review outlines the recent developments of 1,2,4-triazole hybrids with a potential anti-MRSA activity, covering articles published between 2010 and 2020. The mechanisms of action, critical aspects of their design, and structure-activity relationships are also discussed.

Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes.

BACKGROUND: Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. RESULTS: In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. CONCLUSIONS: We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.

Food-Grade Pickering Emulsions: Preparation, Stabilization and Applications.

In recent years, Pickering emulsions have emerged as a new method and have attracted much attention in the fields of food sciences. Unlike conventional emulsions, Pickering emulsions are stabilized by solid particles, which can irreversibly adsorb on the oil-water interface to form a dense film to prevent the aggregation of droplets. The research and development of food-grade solid particles are increasingly favored by scientific researchers. Compared with conventional emulsions, Pickering emulsions have many advantages, such as fewer using amounts of emulsifiers, biocompatibility and higher safety, which may offer feasibility to have broad application prospects in a wide range of fields. In this article, we review the preparation methods, stabilization mechanism, degradation of Pickering emulsions. We also summarize its applications in food sciences in recent years and discuss its future prospects and challenges in this work.

Identification, characterization of two NADPH-dependent erythrose reductases in the yeast Yarrowia lipolytica and improvement of erythritol productivity using metabolic engineering.

BACKGROUND: Erythritol is a four-carbon sugar alcohol with sweetening properties that is used by the agro-food industry as a food additive. In the yeast Yarrowia lipolytica, the last step of erythritol synthesis involves the reduction of erythrose by specific erythrose reductase(s). In the earlier report, an erythrose reductase gene (YALI0F18590g) from erythritol-producing yeast Y. lipolytica MK1 was identified (Janek et al. in Microb Cell Fact 16:118, 2017). However, deletion of the gene in Y. lipolytica MK1 only resulted in some lower erythritol production but the erythritol synthesis process was still maintained, indicating that other erythrose reductase gene(s) might exist in the genome of Y. lipolytica. RESULTS: In this study, we have isolated genes g141.t1 (YALI0D07634g) and g3023.t1 (YALI0C13508g) encoding two novel erythrose reductases (ER). The biochemical characterization of the purified enzymes showed that they have a strong affinity for erythrose. Deletion of the two ER genes plus g801.t1 (YALI0F18590g) did not prevent erythritol synthesis, suggesting that other ER or ER-like enzymes remain to be discovered in this yeast. Overexpression of the newly isolated two genes (ER10 or ER25) led to an average 14.7% higher erythritol yield and 31.2% higher productivity compared to the wild-type strain. Finally, engineering NADPH cofactor metabolism by overexpression of genes ZWF1 and GND1 encoding glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, respectively, allowed a 23.5% higher erythritol yield and 50% higher productivity compared to the wild-type strain. The best of our constructed strains produced an erythritol titer of 190 g/L in baffled flasks using glucose as main carbon source. CONCLUSIONS: Our results highlight that in the Y. lipolytica genome several genes encode enzymes able to reduce erythrose into erythritol. The catalytic properties of these enzymes and their cofactor dependency are different from that of already known erythrose reductase of Y. lipolytica. Constitutive expression of the newly isolated genes and engineering of NADPH cofactor metabolism led to an increase in erythritol titer. Development of fermentation strategies will allow further improvement of this productivity in the future.

Effects of 1-butyl-3-methylimidazolium chloride on the photosynthetic system and metabolism of maize (Zea mays L.) seedlings.

Ionic liquids (ILs) are widely used in various chemical processes. However, a growing number of studies have found that ILs are potentially toxic to different types of living organisms, including crops. The present study analysed the effects of 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) on the photosynthetic system and metabolism of maize seedlings. Results showed that [C4mim]Cl could significantly reduce maize leaf chlorophyll level and cause extensive leaf bleaching. The activity of photosystem II (PSII) was significantly inhibited when seedlings exposed to higher concentration of [C4mim]Cl. The maximum quantum yield of PSII and the potential efficiency of PSII were reduced by 63% and 88% under 800 mg/L [C4mim]Cl treatment in comparison with the control treatment. The RNA sequencing analysis performed to examine gene expression profiles of maize leaves under [C4mim]Cl treatment revealed 639 differentially expressed genes (DEGs), 115 of which were categorized into different metabolic pathways. Among these DEGs, the seven genes involved in the photosynthetic Calvin cycle were down-regulated by [C4mim]Cl exposure. For carbohydrates and amino acids metabolism, the genes for starch synthesis were down-regulated, while the genes for amino acids and protein degradation were up-regulated. The changes observed in these major metabolic pathways might be an important reason for [C4mim]Cl toxicity.

Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is one of the major health concerns worldwide. Farnesoid X receptor (FXR) is considered a therapeutic target for treatment of NAFLD. However, the mechanism by which activation of FXR lowers hepatic triglyceride (TG) levels remains unknown. Here we investigated the role of hepatic carboxylesterase 1 (CES1) in regulating both normal and FXR-controlled lipid homeostasis. Overexpression of hepatic CES1 lowered hepatic TG and plasma glucose levels in both wild-type and diabetic mice. In contrast, knockdown of hepatic CES1 increased hepatic TG and plasma cholesterol levels. These effects likely resulted from the TG hydrolase activity of CES1, with subsequent changes in fatty acid oxidation and/or de novo lipogenesis. Activation of FXR induced hepatic CES1, and reduced the levels of hepatic and plasma TG as well as plasma cholesterol in a CES1-dependent manner. CONCLUSION: Hepatic CES1 plays a critical role in regulating both lipid and carbohydrate metabolism and FXR-controlled lipid homeostasis.

RhoC involved in the migration of neural stem/progenitor cells.

Alzheimer's disease (AD) is characterized by deposition of beta-amyloid peptides (Aß) and progressive loss of neurons. Neural stem/progenitor cells (NSPCs) can proliferate and produce immature neurons even in the brain of AD patients. However, Aß42 significantly decreased the expression of RhoC in NSPCs during the co-incubation (P < 0.01). Treating with RhoC siRNA prevented membrane from protrusion and led to a significant reduction in cell migration in responses to SDF-1. Compared with wild-type mice, the numbers of RhoC-immunoreactive cells in hippocampus and cortex were significantly down-regulated in APP/PS1 mice aged 9 months. The results suggest that Aß42 down-regulates the expression of RhoC in NSPCs in vitro and in vivo; down-regulated RhoC expression results in decreased migration of NSPCs.

Biscarbamate cross-linked low molecular weight Polyethylenimine polycation as an efficient intra-cellular delivery cargo for cancer therapy.

BACKGROUND: A challenge in gene therapy is the efficient delivery of DNA/siRNA to the diseased cells. The physicochemical characteristics of siRNA, such as high molecular weight, negative charges and hydrophilic nature-prevent passive diffusion across the plasma membrane for most cells. A therapeutically feasible carrier for intra-cellular delivery of gene materials should accomplish a series of tasks such as: condensing nucleic acid, protecting nucleic acid from leaking in vivo, facilitating endosome escape and releasing DNA/siRNA to the target site. To meet these requirements, an efficient gene vector based on polycation synthesis for siRNA delivery both in vitro and in vivo was developed. RESULTS: The polymer was synthesized by 1, 4-butanediol bis (chloroformate) and PEI 800 Da to form PEI-Bu which could condense siRNA at the N/P ratio of 38.35 or above. The size of the nanoparticles was 100-300 nm and zeta potential was in the range of 10-30 mV at different N/P ratios. The nanoparticles can achieve the ability of cellular uptake and the silencing efficiency was about 46.63% in SMMC-7721 cell line which was generated to stably express GL3 luciferase gene. The cytotoxicity of the polyplex nanoparticles was almost negligible on SMMC-7721 cells by MTT assay, indicating that the reduced luciferase expression was the effect of RNAi, not the influence of cytotoxicity of polyplexes. The polyplex nanoparticle formulated by PEI-Bu and siRNA at N/P ratio of 115.05 was injected into the SMMC-7721 tumor bearing mice locally and the expression of luciferase can reduce to 63.17% compared with control group. CONCLUSIONS: Results in this study suggested that PEI-Bu polycation might provide a promising solution for siRNA delivery and had the potential in anti-tumor gene therapy.

PLA tissue-engineered scaffolds loaded with sustained-release active substance chitosan nanoparticles: Modeling BSA-bFGF as the active substance.

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.

Preparation of gastrodin modified P(VDF-TrFE)-Eudragit L100-AuNPs nanofiber membranes with piezoelectric property.

In recent years, electroactive nerve conduits made from a blend of P(VDF-TrFE) (poly (vinylidene fluoride-trifluoroethylene)) with other materials have shown significant progress. However, research combining P(VDF-TrFE) conduits with drug delivery systems remains sparse. In this study, we developed a novel gastrodin-loaded P(VDF-TrFE)-Eudragit L100-gold nanoparticles (Gas@PT-EL100-AuNPs) nanofiber membrane. Fabricated through electrospinning technique, this composite membrane aimed to investigate the impacts of gastrodin and AuNPs on its properties. Experimental results indicated that the incorporation of gold nanoparticles significantly reduced the fiber diameter of the membrane and enhanced the overall performance by improving hydrophilicity and piezoelectric properties. Specifically, the addition of AuNPs substantially enhanced the piezoelectric performance of the nanofiber membrane. Furthermore, the inclusion of gastrodin not only improved the membrane's hydrophilicity but also enabled effective release of the neuroprotective drug. These findings suggest that the Gas@PT-EL100-AuNPs nanofiber membrane is a novel biomaterial with potential applications in the repair and treatment of nerve injuries.

Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21.

Previous studies have shown that starvation or consumption of a high fat, low carbohydrate (HF-LC) ketogenic diet induces hepatic fibroblast growth factor 21 (FGF21) gene expression in part by activating the peroxisome proliferator-activated receptor-α (PPARα). Using primary hepatocyte cultures to screen for endogenous signals that mediate the nutritional regulation of FGF21 expression, we identified two sources of PPARα activators (i.e. nonesterified unsaturated fatty acids and chylomicron remnants) that induced FGF21 gene expression. In addition, we discovered that natural (i.e. bile acids) and synthetic (i.e. GW4064) activators of the farnesoid X receptor (FXR) increased FGF21 gene expression and secretion. The effects of bile acids were additive with the effects of nonesterified unsaturated fatty acids in regulating FGF21 expression. FXR activation of FGF21 gene transcription was mediated by an FXR/retinoid X receptor binding site in the 5'-flanking region of the FGF21 gene. FGF19, a gut hormone whose expression and secretion is induced by intestinal bile acids, also increased hepatic FGF21 secretion. Deletion of FXR in mice suppressed the ability of an HF-LC ketogenic diet to induce hepatic FGF21 gene expression. The results of this study identify FXR as a new signaling pathway activating FGF21 expression and provide evidence that FXR activators work in combination with PPARα activators to mediate the stimulatory effect of an HF-LC ketogenic diet on FGF21 expression. We propose that the enhanced enterohepatic flux of bile acids during HF-LC consumption leads to activation of hepatic FXR and FGF19 signaling activity and an increase in FGF21 gene expression and secretion.

Human cytomegalovirus in cancer: the mechanism of HCMV-induced carcinogenesis and its therapeutic potential.

Cancer is one of the leading causes of death worldwide. Human cytomegalovirus (HCMV), a well-studied herpesvirus, has been implicated in malignancies derived from breast, colorectal muscle, brain, and other cancers. Intricate host-virus interactions are responsible for the cascade of events that have the potential to result in the transformed phenotype of normal cells. The HCMV genome contains oncogenes that may initiate these types of cancers, and although the primary HCMV infection is usually asymptomatic, the virus remains in the body in a latent or persistent form. Viral reactivation causes severe health issues in immune-compromised individuals, including cancer patients, organ transplants, and AIDS patients. This review focuses on the immunologic mechanisms and molecular mechanisms of HCMV-induced carcinogenesis, methods of HCMV treatment, and other studies. Studies show that HCMV DNA and virus-specific antibodies are present in many types of cancers, implicating HCMV as an important player in cancer progression. Importantly, many clinical trials have been initiated to exploit HCMV as a therapeutic target for the treatment of cancer, particularly in immunotherapy strategies in the treatment of breast cancer and glioblastoma patients. Taken together, these findings support a link between HCMV infections and cellular growth that develops into cancer. More importantly, HCMV is the leading cause of birth defects in newborns, and infection with HCMV is responsible for abortions in pregnant women.

Multifunctional electrospun membranes with hydrophilic and hydrophobic gradients property for wound dressing.

Achieving sustained and stable release of macromolecular antibacterial agents and unidirectional transport of liquids in targeted environment is still a challenge to be addressed in the management of wounds with large amounts of tissue exudates. In this work, a multilayer electrospun membrane (ethylcellulose-ethylcellulose/gelatin-quercetin/Eudragit L-100/polyethylene glycol, EC-EC/Gel-Q/EL/PEG) was designed with hydrophobic-hydrophilic gradients and drug sustained-release properties controlled by self-pumping effect and prepared using sequential electrospinning technology. The capillary force of different layers in the multilayer membrane could be controlled by precisely tuning the polymer concentrations of the inner and middle layers to extract water directly from hydrophobic inner ethylcellulose (EC) layer to hydrophilic middle ethylcellulose/gelatin (EC/Gel) layer. The droplets could not penetrate the hydrophobic side, but the drug molecules in the outer layer quercetin-loaded Eudragit L-100 (Q/EL/PEG) membrane moved after absorbing a large amount of water. The drug release behavior of multilayer wound dressing mainly followed the Korsmeyer-Peppas model. This multifunctional electrospun membrane could rapidly drive the biofluid outflow, effectively block the invasion of external contaminants and continuously release anti-inflammatory drugs, without any obvious cytotoxicity to mouse fibroblast cells. Hence, the above results indicate the excellent therapeutic potential of the proposed biomaterial as a wound dressing for diabetic patients.

Advances in Large Gap Peripheral Nerve Injury Repair and Regeneration with Bridging Nerve Guidance Conduits.

Peripheral nerve injury is a common complication of accidents and diseases. The traditional autologous nerve graft approach remains the gold standard for the treatment of nerve injuries. While sources of autologous nerve grafts are very limited and difficult to obtain. Nerve guidance conduits are widely used in the treatment of peripheral nerve injuries as an alternative to nerve autografts and allografts. However, the development of nerve conduits does not meet the needs of large gap peripheral nerve injury. Functional nerve conduits can provide a good microenvironment for axon elongation and myelin regeneration. Herein, the manufacturing methods and different design types of functional bridging nerve conduits for nerve conduits combined with electrical or magnetic stimulation and loaded with Schwann cells, etc., are summarized. It summarizes the literature and finds that the technical solutions of functional nerve conduits with electrical stimulation, magnetic stimulation and nerve conduits combined with Schwann cells can be used as effective strategies for bridging large gap nerve injury and provide an effective way for the study of large gap nerve injury repair. In addition, functional nerve conduits provide a new way to construct delivery systems for drugs and growth factors in vivo.

Hepatic hepatocyte nuclear factor 4α is essential for maintaining triglyceride and cholesterol homeostasis.

OBJECTIVE: Loss-of-function mutations in human hepatocyte nuclear factor 4α (HNF4α) are associated with maturity-onset diabetes of the young and lipid disorders. However, the mechanisms underlying the lipid disorders are poorly understood. In this study, we determined the effect of acute loss or augmentation of hepatic HNF4α function on lipid homeostasis. METHODS AND RESULTS: We generated an adenovirus expressing LacZ (Ad-shLacZ) or short hairpin RNA of Hnf4α (Ad-shHnf4α). Tail vain injection of C57BL/6J mice with Ad-shHnf4α reduced hepatic Hnf4α expression and resulted in striking phenotypes, including the development of fatty liver and a >80% decrease in plasma levels of triglycerides, total cholesterol, and high-density lipoprotein cholesterol. These latter changes were associated with reduced hepatic lipogenesis and impaired very-low-density lipoprotein secretion. Deficiency in hepatic Hnf4α did not affect intestinal cholesterol absorption despite decreased expression of genes involved in bile acid synthesis. Consistent with the loss-of-function data, overexpression of Hnf4α induced numerous genes involved in lipid metabolism in isolated primary hepatocytes. Interestingly, many of these HNF4α-regulated genes were not induced in wild-type mice that overexpressed hepatic Hnf4α. Because of selective gene regulation, mice overexpressing hepatic Hnf4α had unchanged plasma triglyceride levels and decreased plasma cholesterol levels. CONCLUSIONS: Loss of hepatic HNF4α results in severe lipid disorder as a result of dysregulation of multiple genes involved in lipid metabolism. In contrast, augmentation of hepatic HNF4α activity lowers plasma cholesterol levels but has no effect on plasma triglyceride levels because of selective gene regulation. Our data indicate that hepatic HNF4α is essential for controlling the basal expression of numerous genes involved in lipid metabolism and is indispensable for maintaining normal lipid homeostasis.

The Antioxidant Effect of the Metal and Metal-Oxide Nanoparticles.

Inorganic nanoparticles, such as CeO3, TiO2 and Fe3O4 could be served as a platform for their excellent performance in antioxidant effect. They may offer the feasibility to be further developed for their smaller and controllable sizes, flexibility to be modified, relative low toxicity as well as ease of preparation. In this work, the recent progress of these nanoparticles were illustrated, and the antioxidant mechanism of the inorganic nanoparticles were introduced, which mainly included antioxidant enzyme-mimetic activity and antioxidant ROS/RNS scavenging activity. The antioxidant effects and the applications of several nanoparticles, such as CeO3, Fe3O4, TiO2 and Se, are summarized in this paper. The potential toxicity of these nanoparticles both in vitro and in vivo was well studied for the further applications. Future directions of how to utilize these inorganic nanoparticles to be further applied in some fields, such as medicine, cosmetic and functional food additives were also investigated in this paper.

The role of essential oils in maintaining the postharvest quality and preservation of peach and other fruits.

Fruits are highly susceptible to postharvest losses induced majorly by postharvest diseases. Peach are favored by consumers because of their high nutritional value and delicious taste. However, it was easy to be affected by fungal infection. The current effective method to control postharvest diseases of fruits is to use chemical fungicides, but these chemicals may cause adverse effects on human health and the residual was potentially harmful to nature and the environment. So, it is especially important to develop safe, non-toxic, and highly effective strategies for the preservation of the fruits. Essential oil, as a class of the natural bacterial inhibitor, has been proven to exhibit strong antibacterial activity, low toxicity, environmental friendliness, and induce fruit resistance to microorganism, which could be recognized as one of the alternatives to chemical fungicides. This paper reviews the research progress of essential oils (Eos) in the storage and preservation of fruits, especially the application in peach, as well as the application in active packaging such as edible coatings, microcapsules, and electrospinning loading. Electrospinning can prepare a variety of nanofibers from different viscoelastic polymer solutions, and has broad application prospects. The paper especially summarizes the application of the new Eos technology on peach. The essential oil with thymol, eugenol, and carvacrol as the main components has a better inhibitory effect on the postharvest disease of peaches, and can be further applied. PRACTICAL APPLICATIONS: As an environmentally friendly natural antibacterial agent, essential oil can be used as a substitute for chemical preservatives to keep fruits fresh. This paper summarizes the different preservation methods of essential oils for fruits, and especially summarizes the different preservation methods of essential oils for peaches after harvesting, as well as their inhibitory effects on pathogenic fungi. It could provide ideas for preservation of fruits and vegetables by essential oils.

Study on the Preparation, Characterization, and Stability of Freeze-Dried Curcumin-Loaded Cochleates.

Curcumin (CUR), a polyphenolic substance extracted from plants, has extensive pharmacological activities. However, CUR is difficult to be absorbed in the body due to its poor stability and low solubility. Studies have found that cochleates can be used as a new delivery system to encapsulate bioactive agents for the purpose of improving its stability and bioavailability. In this study, thin-film dispersion and trapping methods were used to prepare curcumin-loaded cochleates (CUR-Cochs). Then CUR-Cochs were characterized and the encapsulation efficiency was determined by HPLC. In addition, the freeze-drying process of CUR-Cochs was studied and related characterization was performed. CCK-8 assay was used to detect the cytotoxicity of cochleates carrier. Additionally, H2O2-induced cellular oxidative damage model were used to evaluate its antioxidant capacity. The results showed that the structure of CUR-Cochs was a spiral cylinder with an average particle size of 463.8 nm and zeta potential of -15.47 mV. The encapsulation efficiency was the highest (83.66 ± 0.8)% with 1:50 CUR-to-lipid mass ratio. In vitro results showed that cochleates had negligible cytotoxicity and owned antioxidant capacity, which provided the possibility for their applications in food and medicine. In general, the method herein might be a promising method to encapsulate CUR for further use as a bioactive agent in functional foods.

Preparation of curcumin-loaded cochleates: characterisation, stability and antioxidant properties.

Curcumin (CUR) has a wide range of applications in functional foods. However, it has some disadvantages such as poor water solubility and stability. To solve these problems, CUR was encapsulated into cochleates with an encapsulation efficiency of 83.66% and a diameter of about 403.9 nm. The study found that the stability of CUR-loaded cochleates (CUR-Cochs) was improved when compared with that of the curcumin-loaded liposomes (CUR-Lipos). Additionally, it showed that the DPPH scavenging ability of CUR-Cochs was equivalent to free CUR. In addition, 3 µM CUR-Cochs could significantly reduce the MDA content and the LDH release, and increased SOD activity in the H2O2 induced NIH3T3 cell oxidative damage model. The expression of Nrf2 and NQO1 proteins were obviously increased in the CUR-Cochs group, indicating that CUR-Cochs could effectively reduce NIH3T3 cell damage caused by H2O2. The CUR-Cochs could improve the stability of CUR with a desired anti-oxidation ability, which may mean that it is feasible for it to be applied further in functional foods.