Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.

This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.

Zein nanoparticles containing ceftazidime and tobramycin: antibacterial activity against Gram-negative bacteria.

Aims: This work describes the encapsulation of ceftazidime and tobramycin in zein nanoparticles (ZNPs) and the characterization of their antibacterial and antibiofilm activities against Gram-negative bacteria. Materials & methods: ZNPs were synthesized by nanoprecipitation. Cytotoxicity was assessed by MTT assay and antibacterial and antibiofilm assays were performed by broth microdilution and violet crystal techniques. Results: ZNPs containing ceftazidime (CAZ-ZNPs) and tobramycin (TOB-ZNPs) showed drug encapsulation and thermal stability. Encapsulation of the drugs reduced their cytotoxicity 9-25-fold. Antibacterial activity, inhibition and eradication of biofilm by CAZ-ZNPs and TOB-ZNPs were observed. There was potentiation when CAZ-ZNPs and TOB-ZNPs were combined. Conclusion: CAZ-ZNPs and TOB-ZNPs present ideal physical characteristics for in vivo studies of antibacterial and antibiofilm activities.

A nanotechnology product was developed to treat diseases caused by bacteria. This prototype showed the ideal characteristics and could be administered by ingestion through the mouth, aspiration through the nose or injection into the veins. The prototype did not harm or kill human cells. It killed the bacteria and prevented the formation of a type of protection against antibiotics that bacteria can produce, called a biofilm. Nanotechnology products are a promising alternative for the treatment of bacterial infections.

[Preparation and Performance Study of a Novel Antibacterial Hemostatic Chitosan Sponge]. / ä¸€ç§è½½è¯å£³èšç³–æŠ—èŒæ­¢è¡€æµ·ç»µçš„åˆ¶å¤‡åŠå ¶æ€§èƒ½ç ”ç©¶.

Objective: To create a novel chitosan antibacterial hemostatic sponge (NCAHS) and to evaluate its material and biological properties. Methods: Chitosan, a polysaccharide, was used as the sponge substrate and different proportions of sodium tripolyphosphate (STPP), glycerol, and phenol sulfonyl ethylamine were added to prepare the sponges through the freeze-drying method. The whole-blood coagulation index (BCI) was used as the screening criterion to determine the optimal concentrations of chitosan and the other additives and the hemostatic sponges were prepared accordingly. Zein/calcium carbonate (Zein/CaCO3) composite microspheres loaded with ciprofloxacin hydrochloride were prepared and added to the hemostatic sponges to obtain NCAHS. Scanning electron microscope was used to observe the microscopic morphology and porosity of the NCAHS. The water absorption rate, in vitro antibacterial susceptibility rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), in vitro coagulation performance, and hemocompatibility of NCAHS were examined. The coagulation performance of NCAHS was evaluated by using rabbit liver injury and rabbit auricular artery hemorrhageear models and commercial hemostatic sponge (CHS) was used as a control. The in vivo biocompatibility, including such aspects as cytotoxicity, skin irritation in animals, and acute in vivo toxicity, of the NCAHS extracts was examined by using as a reference the national standards for biological evaluation of medical devices. Results: The NCAHS prepared with 1.5% chitosan (W/V), 0.01% STPP (W/V), 0% glycerol (V/V), 0.15% phenol-sulfonyl-ethylamine (V/V), Zein and CaCO3 at the mixing ratio of 5∶1 (W/W), Zein at the final mass concentration of 2.5 g/L, and ethanol at the final concentration of 17.5% (V/V) were fine and homogeneous, possessing a honeycomb-like porous structure with a pore size of about 200 µm. The NCAHS thus prepared had the lowest BCI value. The water absorption ([2362.16±201.15] % vs. [1102.56±91.79]%) and in vitro coagulation performance (31.338% vs. 1.591%) of NCAHS were significantly better than those of CHS (P<0.01). Tests with the in vivo auricular artery hemorrhage model ([36.00±13.42] s vs. [80.00±17.32] s) and rabbit liver bleeding model ([30.00±0] s vs. [70.00±17.32] s) showed that the hemostasis time of NCAHS was significantly shorter than that of CHS (P<0.01). NCAHS had significant inhibitory ability against S. aureus and E. coli. In addition, NCAHS showed good in vitro and in vivo biocompatibility. Conclusion: NCAHS is a composite sponge that shows excellent antimicrobial properties, hemostatic effect, and biocompatibility. Therefore, its extensive application in clinical settings is warranted.

A Janus Gelatin Sponge with a Procoagulant Nanoparticle-Embedded Surface for Coagulopathic Hemostasis.

Apart from the wide and safe application of natural polymer-based hemostatic materials/devices, it is still desirable to develop new types of hemostatic materials that can achieve both potent coagulopathic hemostasis and a facile preparation process. In this work, one Janus gelatin sponge (J-ZGS) is readily constructed for both coagulation-dependent and coagulopathic hemostasis by embedding zein nanoparticles on the surface of a self-prepared gelatin sponge (S-GS): zein nanoparticles were facilely prepared by an antisolvent method to achieve procoagulant blood-material interactions, while S-GS was prepared by freeze-drying a foaming gelatin solution. Due to the distinct secondary structure, the optimal zein nanoparticles possessed a higher in vitro hemostatic property than the pristine zein powder and other nanoparticles, the underlying mechanism of which was revealed as the superior RBC/platelet adhesion property in the presence/absence of plasma proteins. Compared with S-GS and a commercial gelatin sponge, J-ZGS achieved a significantly higher in vitro hemostatic property and similarly good blood compatibility/cytocompatibility. Moreover, in vivo artery-injury models confirmed the outstanding hemostatic performance of J-ZGS under both coagulation-dependent and coagulopathic conditions. Our work offers an appealing approach for developing potent hemostatic sponges from natural polymer-based nanoparticles that could be further extended to versatile hemostatic materials for coagulopathic hemostasis.

Zein-Based Nanoparticles Improve the Therapeutic Efficacy of a TrkB Agonist toward Alzheimer's Disease.

The brain-derived neurotrophic factor (BDNF)/TrkB pathway plays a crucial role in neural plasticity and neuronal survival but is often deficient in neurodegenerative diseases like Alzheimer's disease (AD). CF3CN acts as a specific TrkB agonist that displays therapeutic effects in the AD mouse model, but its brain/plasma ratio (B/P ratio) distribution is not satisfactory. To increase its brain exposure, we synthesized several derivatives and employed nanoparticle (NP) formulation to optimize the most potent #2 derivative's in vivo PK profiles. We generated stable #2-loaded zein/lactoferrin composite NPs (#2/zein/LF) using the antisolvent co-precipitation method. In vivo PK studies revealed that nanoencapsulation improved #2's oral bioavailability by approximately 2-fold and significantly enhanced its plasma Cmax and t1/2, but the brain profiles were comparable. Pharmacodynamics showed that #2/zein/LF activates TrkB signaling that phosphorylates asparagine endopeptidase (AEP) T322 and decreases its enzymatic activity, resulting in reduced AEP-cleaved amyloid precursor protein and Tau fragments in the brains of AD mice, correlating with its PK profiles. After 3 months of treatment in 3xTg mice, #2/zein/LF decreased AD pathologies and alleviated cognitive dysfunction. Hence, zein/LF composite nanoencapsulation is a promising drug delivery method for improving the PK profiles of a potential preclinical candidate for treating neurodegenerative diseases.

Kaempferol-loaded bioactive glass-based scaffold for bone tissue engineering: in vitro and in vivo evaluation.

Due to the increasing prevalence of bone disorders among people especially in average age, the future of treatments for osseous abnormalities has been illuminated by scaffold-based bone tissue engineering. In this study, in vitro and in vivo properties of 58S bioactive glass-based scaffolds for bone tissue engineering (bare (B.SC), Zein-coated (C.SC), and Zein-coated containing Kaempferol (KC.SC)) were evaluated. This is a follow-up study on our previously published paper, where we synthesized 58S bioactive glass-based scaffolds coated with Kaempferol-loaded Zein biopolymer, and characterized from mostly engineering points of view to find the optimum composition. For this aim, in vitro assessments were done to evaluate the osteogenic capacity and biological features of the scaffolds. In the in vivo section, all types of scaffolds with/without bone marrow-derived stem cells (BMSC) were implanted into rat calvaria bone defects, and potential of bone healing was assessed using imaging, staining, and histomorphometric analyses. It was shown that, Zein-coating covered surface cracks leading to better mechanical properties without negative effect on bioactivity and cell attachment. Also, BMSC differentiation proved that the presence of Kaempferol caused higher calcium deposition, increased alkaline phosphatase activity, bone-specific gene upregulation in vitro. Further, in vivo study confirmed positive effect of BMSC-loaded KC.SC on significant new bone formation resulting in complete bone regeneration. Combining physical properties of coated scaffolds with the osteogenic effect of Kaempferol and BMSCs could represent a new strategy for bone regeneration and provide a more effective approach to repairing critical-sized bone defects.

Zein-maltodextrin nanocomplex based dissolving microneedle: A promising approach for Paliperidone palmitate delivery.

Researchers are looking at microneedle devices as a possible solution to the problems with poor patient compliance and severe gastrointestinal side effects associated with conventional oral or injectable techniques for treating schizophrenia. Microneedles (MNs) may be an effective approach for transdermal drug delivery of antipsychotic drugs. We fabricated polyvinyl alcohol (PVA) microneedles loaded with paliperidone palmitate (PLDN) nanocomplex and studied their therapeutic potency for schizophrenia. We demonstrated that PLDN nanocomplex-loaded MNs had a pyramidal shape with high mechanical strength, which allowed us to successfully deliver PLDN into the skin and improve permeation behavior ex-vivo. Microneedling enhanced the concentration of PLDN in plasma and brain tissue as compared with the plain drug as observed. In addition, the therapeutic effectiveness was significantly improved by MNs with the capability of extended release. According to the findings of our study, the nanocomplex-loaded microneedle-mediated transdermal delivery of PLDN has the potential to be a novel treatment for schizophrenia.

Natural and biocompatible dressing unit based on tea carbon dots modified core-shell electrospun fiber for diabetic wound disinfection and healing.

Wound infection and healing in patients with diabetes is one of the complex problems in trauma treatment. Therefore, designing and preparing an advanced dressing membrane for treating the wounds of such patients is essential. In this study, a zein film with biological tea carbon dots (TCDs) and calcium peroxide (CaO2) as the main components for promoting diabetic wound healing was prepared by an electrospinning technique, which combines the advantages of natural degradability and biosafety. CaO2 is a biocompatible material with a microsphere structure that reacts with water to release hydrogen peroxide and calcium ions. TCDs with a small diameter were doped in the membrane to mitigate its properties while improving the antibacterial and healing effects of the membrane. TCDs/CaO2 was mixed with ethyl cellulose-modified zein (ZE) to prepare the dressing membrane. The antibacterial properties, biocompatibility and wound-healing properties of the composite membrane were investigated by antibacterial experiment, cell experiment and a full-thickness skin defect. TCDs/CaO2 @ZE exhibited significant anti-inflammatory and wound healing-promoting properties in diabetic rats, without any cytotoxicity. This study is meaningful in developing a natural and biocompatible dressing membrane for diabetic wound healing, which shows a promising application in wound disinfection and recovery in patients with chronic diseases.

Systemic effects of oral tolerance in bone healing.

Bone fractures cause acute inflammation that, despite being important for initial repair, may delay the healing of the damaged bone. Parenteral injection of dietary protein has been shown to decrease inflammation and accelerate the repair of skin wounds and other inflammatory pathologies. Thus, our aim was to evaluate whether the intraperitoneal (i.p.) immunization with zein, an abundant protein in rodent chow, would favor bone healing. Wistar rats received i.p. immunization: saline (SG), adjuvant (AG) and zein associated with adjuvant (ZG). Then, a 2 mm of defect bone was performed on the right tibia, and on days 7, 14, 28 and 45 thereafter, analyses were performed. The results showed that the injection of zein reduced inflammation without impairing bone mineralization. Moreover, biomechanical tests demonstrated higher levels of maximum force (N) in ZG, indicating better mechanical resistance in relation to the others. The computerized tomography also indicated lower levels of medullary content in the ZG than in the SG, suggesting the absence of trabeculae in the medullary region in the ZG. These findings suggest that the injection of zein in previously tolerated animals may improve bone repair, leading to mechanically functional bone formation.

Electrospun Mucoadhesive Zein/PVP Fibroporous Membrane for Transepithelial Delivery of Propranolol Hydrochloride.

Mucoadhesive drug delivery systems have been extensively studied to effectively reduce the limitations of conventional drug delivery systems. Zein and polyvinyl pyrrolidone (PVP) are appraised for mucoadhesive properties. This study focuses on developing a mechanically stable zein/PVP electrospun membrane for propranolol hydrochloride (PL) transport. Fourier transform infrared, Raman spectra, and swelling studies gave evidence for PVP crosslinking, whereas circular dichroism spectroscopy revealed crosslinking of zein owing to the conformational change from α-helix to ß-sheet. A 10 h thermal treatment of zein/PVP imparted 3.92 ± 0.13 MPa tensile strength to the matrix. Thermally crosslinked electrospun zein/PVP matrix showed 22.1 ± 0.1 g mm work of adhesion in porcine buccal mucosa tissue. Qualitative and quantitative evaluation of cytotoxicity in RPMI 2650 has been carried out. The in vitro drug release profile of PL from thermally crosslinked zein/PVP best fitted with the Korsmeyer-Peppas model. Immunostaining of ß-catenin adherens junctional protein confirmed the absence of paracellular transport through the junctional opening. Still, drug permeation was observed through the porcine buccal mucosa, attributed to the transcellular transport of PL owing to its lipophilicity. The ex vivo permeation of PL through porcine buccal mucosa was also evaluated.

Intensification of resveratrol cytotoxicity, pro-apoptosis, oxidant potentials in human colorectal carcinoma HCT-116 cells using zein nanoparticles.

Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells. ZN-RSV NPs were developed and assayed for particle size analysis and RSV diffusion. The selected formula obtained 137.6 ± 8.3 nm as mean particle size, 29.4 ± 1.8 mV zeta potential, 92.3 ± 3.6% encapsulation efficiency. IC50 of the selected formula was significantly lower against HCT-116 cells versus Caco-2 cells. Also, significantly enhanced cellular uptake was generated from RSV-ZN NPs versus free RSV. Enhanced apoptosis was concluded due to increased percentage cells in G2-M and pre-G1 phases. The pro-apoptotic potential was explained by caspase-3 and cleaved caspase-3 increased mRNA expression in addition to NF-κB and miRNA125b decreased expression. Biochemically, ZN-RSV NPs induced oxidative stress as demonstrated by enhanced reactive oxygen species (ROS) generation and endothelial nitric oxide synthase (eNOS) isoenzyme increased levels. Conclusively, ZN-RSV NPs obtained cell cycle inhibition supported with augmented cytotoxicity, uptake and oxidative stress markers levels in HCT-116 tumor cells in comparison with free RSV. These results indicated intensified chemopreventive profile of RSV due to effective delivery utilizing ZN nano-dispersion against colorectal carcinoma HCT-116 cells.

Effect of zein and zein-Peganum harmala extract coatings of eggshell on the internal quality of eggs and control of Salmonella enteritidis.

The high nutritional value of egg makes it vital to the human diet. Salmonella enteritidis is one of the major global causes of foodborne enteritis in humans. The chicken intestine is the main source of S. enteritidis. Therefore, eggs play an important role in the transmission of salmonellosis. In this study, we evaluated the effectiveness of coatings made of zein either alone or in combination of hydro-alcoholic extract of Peganum harmala on the quality of eggs and control of S. enteritidis at 7°C during a period of 28 days. Results demonstrated that both types of the coating significantly improved the physicochemical properties of eggs including weight loss, Haugh unit, and yolk index compared to controls during storage. However, neither of coatings resulted in significant changes in yolk color and pH (p < 0.05). Both types of coating caused two log CFU/ml reductions in S. enteritidis population from the first day and eliminated the contamination at the end of the experiment (for 28 days). Salmonella elimination occurred at day 21 for zein-plant extract coating. Our findings demonstrate zein coating can be an appropriate approach for maintaining the quality of eggs during shelf life and an effective and economic strategy for control of S. enteritidis in eggs. PRACTICAL APPLICATION: This study shows that the application of zein coating can preserve the internal quality and freshness of eggs during storage. Moreover, zein coating is a highly effective strategy in the control of Salmonella. This method can be used on a commercial scale for enhancing the safety and quality of eggs.

Nitric Oxide-Releasing Nanofibrous Scaffolds Based on Silk Fibroin and Zein with Enhanced Biodegradability and Antibacterial Properties.

Clinical applications of scaffolds and implants have been associated with bacterial infection resulting in impaired tissue regeneration. Nanofibers provide a versatile structure for both antimicrobial molecule delivery and tissue engineering. In this study, the nitric oxide (NO) donor molecule S-nitrosoglutathione (GSNO) and the natural biodegradable polymer zein (ZN) were combined with silk fibroin (SF) to develop antibacterial and biodegradable nanofibrous scaffolds for tissue engineering applications. The compatibility and intermolecular interactions of SF and ZN were studied using differential scanning calorimetry and Fourier transform infrared spectroscopy. The incorporation of ZN increased the hydrophobicity of the fibers and resulted in a more controlled and prolonged NO release profile lasting for 48 h. Moreover, the degradation kinetics of the fibers was significantly improved after blending with ZN. The results of tensile testing indicated that the addition of ZN and GSNO had a positive effect on the strength and stretchability of SF fibers and did not adversely affect their mechanical properties. Finally, due to the antibacterial properties of both NO and ZN, the SF-ZN-GSNO fibers showed a synergistically high antibacterial efficacy with 91.6 ± 2.5% and 77.5 ± 3.1% reduction in viability of adhered Staphylococcus aureus and Escherichia coli after 24 h exposure, respectively. The developed NO-releasing fibers were not only antibacterial but also non-cytotoxic and successfully enhanced the proliferation and growth of fibroblast cells, which was quantitatively studied by a CCK-8 assay and visually observed through fluorescent staining. Overall, SF-ZN-GSNO fibers developed in this study were biodegradable and highly antibacterial and showed great cytocompatibility with fibroblasts, indicating their promising potential for a range of tissue engineering and medical device applications.

Antimicrobial effects of thymol-loaded phytoglycogen/zein nanocomplexes against foodborne pathogens on fresh produce.

In this study, thymol-loaded hydrophobically modified phytoglycogen/zein nanocomplexes with a particle size around 100 nm were developed for improving microbial safety of fresh produce. The antimicrobial activities, including the determination of minimum inhibitory and bactericidal concentration, growth kinetic curves, and inhibition zone of the nanocomplexes against foodborne pathogens (Listeria monocytogenes, Salmonella enteritidis, and Escherichia coli) were evaluated. The results showed that the antimicrobial activities of the nanocomplexes were significantly stronger than that of free thymol control (without encapsulation), and the antimicrobial efficacy remained unchanged after storage at 4 °C for 60 days. The morphological results from atomic force microscope revealed that small micellar blebs were formed at the surface of bacteria after treatment with nanocomplexes and the gradual disappearance of the cell boundary indicated the occurrence of cytolysis. The potential applications of this nanocomplex as disinfectant agent in wash water were evaluated on different types of fresh produce (lettuce, cantaloupe, and strawberries). Notably, the nanocomplexes also demonstrated efficacy in biofilm removal. Findings from this study clearly demonstrated that the thymol-loaded nanocomplexes hold promising potential for the disinfection of fresh produce to improve their microbial safety and quality.

Preparation and evaluation of chitosan/polyvinylpyrrolidone/zein composite hemostatic sponges.

Trauma-related excessive bleeding is one of the leading causes of death. Chitosan (CS) sponges have unique advantages in the treatment of massive bleeding, but their application is limited by poor stability and toxic crosslinking agent. In this work, chitosan/polyvinylpyrrolidone/zein (CS/PVP/Zein) sponges with macroporous structure were prepared, which exhibited rapid water absorption capacity and water-triggered expanding property with low cytotoxicity and low hemolysis ratio. In vitro blood coagulation experiments showed that CS/PVP/Zein sponges could clot blood significantly faster than commercial surgical gauze. Further investigation of the hemostatic mechanism suggested that the CS/PVP/Zein sponges could accelerate coagulation by promoting attachment of erythrocytes, activation of platelets, and rapid plasma protein absorption. Prepared sponges were also found effective in the rat femoral artery transection model to control bleeding. Overall, the CS/PVP/Zein sponges exhibited the potential to control trauma-related hemorrhage.

Eugenol embedded zein and poly(lactic acid) film as active food packaging: Formation, characterization, and antimicrobial effects.

Biodegradable packaging is more eco-friendly compared with the synthetic plastics. To improve the physical properties of the zein films, poly(lactic acid) (PLA) was mixed with zein to make a biodegradable blend film. The composition of the film with the best properties was the one with zein and PLA in the mass ratio of 1:1 with the addition of 20% poly(ethylene glycol) as the plasticizer. The incorporation of PLA significantly increased the elongation, reduced the tensile strength, and decreased the water vapor and gas permeabilities of zein films. The antimicrobial agent eugenol added in the film significantly inhibited the growth of both S. aureus and E. coli. The migration tests were conducted to confirm the safety of the blend films. This is the first-time report of zein-PLA blend film. The antimicrobial zein-PLA-eugenol film with enhanced mechanical and barrier properties has a high potential as active biodegradable food packaging.

Zein-induced immune response and modulation by size, pore structure and drug-loading: Application for sciatic nerve regeneration.

Zein is a biodegradable material with great potential in biomedical applications. However, as a plant-derived protein material, body's immune response is the key factor to determine its clinical performance. Herein, for the first time, the zein-induced immune response is evaluated systemically and locally, comparing with typical materials including alginate (ALG), poly(lactic-co-glycolic) acid (PLGA) and polystyrene (PS). Zein triggers an early inflammatory response consistent with the non-degradable PS, but this response decreases to the same level of the biosafe ALG and PLGA with zein degradation. Changing sphere sizes, pore structure and encapsulating dexamethasone can effectively modulate the zein-induced immune response, especially the pore structure which also inhibits neutrophil recruitment and promotes macrophages polarizing towards M2 phenotype. Thus, porous zein conduits with high and low porosity are further fabricated for the 15 mm sciatic nerve defect repair in rats. The conduits with high porosity induce more M2 macrophages to accelerate nerve regeneration with shorter degradation period and better nerve repair efficacy. These findings suggest that the pore structure in zein materials can alleviate the zein-induced early inflammation and promote M2 macrophage polarization to accelerate nerve regeneration. STATEMENT OF SIGNIFICANCE: Zein is a biodegradable material with great potential in biomedical applications. However, as a plant protein, its possible immune response in vivo is always the key issue. Until now, the systemic study on the immune responses of zein in vivo is still very limited, especially as an implant. Herein, for the first time, the zein-induced immune response was evaluated systemically and locally, comparing with typical biomaterials including alginate, poly(lactic-co-glycolic) acid and polystyrene. Changing sphere sizes, pore structure and encapsulating dexamethasone could effectively modulate the zein-induced immune response, especially the pore structure which also inhibited neutrophil recruitment and promoted macrophages polarizing towards M2 phenotype. Furthermore, the pore structure in zein nerve conduits was proved to alleviate the early inflammation and promote M2 macrophage polarization to accelerate nerve regeneration.

SCLAREIN (SCLAREol contained in zeIN) nanoparticles: Development and characterization of an innovative natural nanoformulation.

Sclareol is a labdane diterpene which carries on a broad range of biological activities. However, its poor water solubility and bioavailability are the foremost drawbacks that limit its application in therapeutics. The purpose of this investigation was to develop a natural nanoformulation made up of a biopolymer i.e. zein and sclareol in order to address this issue and to enhance the pharmacological efficacy of the drug. The sclarein nanoparticles (sclareol-loaded zein nanosystems) showed a typical monomodal pattern, characterized by a mean diameter of ~120 nm, a narrow size distribution and a surface charge of ~-30 mV. The evaluation of the entrapment efficiency and the drug-loading capacity of the nanosystems demonstrated the noteworthy ability of the protein matrix to hold sclareol while allowing a gradual release of the compound over time. The nanosystems increased the cytotoxicity of sclareol at a drug concentration of ≥5 µM with respect to the free compound after just 24 h incubation against various cancer cell lines. Indeed, the interaction of tritiated sclarein formulations with cells showed a time-dependent cell uptake of the nanosystems commencing as early as 1 h from the onset of incubation, favouring a significant decrease of the efficacious concentration of the drug.

Improvement of mechanical properties of zein porous scaffold by quenching/electrospun fiber reinforcement.

As a novel bone substitute material, zein-based scaffolds (ZS) should have suitable mechanical properties and porosity. ZS has shown good compressive properties matching cancellous bone, but there is still a demand to improve its mechanical properties, especially tensile and bending properties without adding plasticizers. The present study explored two simple and environment-friendly factors for this purpose: fiber reinforcement and quenching. Addition of electrospun zein fibers enhanced all mechanical properties significantly including compressive, tensile, and bending moduli; compressive and bending strengths of ZS with both higher (70-80%) and lower (50-60%) porosities, no matter whether heating treated or not treated. Especially, all these parameters were further enhanced significantly by addition of heating treated fibers. AFM provided evidence that high temperature modification could significantly alter the micro-elastic properties of zein electrospun fibers, i.e., increased stiffness of fibers. Quenching treatment also enhanced compressive, tensile, and bending strengths significantly. Finally, quenching treated ZS were implanted into critical-sized bone defects (15 mm) of the rabbit model to compare the repair efficacy with a commercial ß-tricalcium phosphate product. The results demonstrated that there were no remarkable differences in bone reconstructions between these two materials.

Insulin- and cholic acid-loaded zein/casein-dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin.

Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surfaces were fabricated to enhance the oral absorptions of insulin in the intestine and in the liver which is the primary action organ of endogenous insulin. In the nanoparticles, zein acted as cement to embed insulin, cholic acid and casein by hydrophobic interactions. The hydrophilic dextran conjugated to casein by the Maillard reaction was located on the nanoparticle surface. The nanoparticles had an insulin loading efficiency of 74.6%, a cholic acid loading efficiency of 55.1% and a hydrodynamic diameter of 267 nm. The dextran significantly increased the disperse stability of the nanoparticles, protected the loaded insulin from hydrolysis in digestive juices, and increased the trans-mucus permeability of the insulin. The embedded cholic acid molecules were consecutively exposed to the surface when the nanoparticles were gradually eroded by proteases. The exposed cholic acid promoted the absorptions of the nanoparticles in the ileum and liver via bile acid transporters. The effect of pretreated lymphatic transport inhibitor cycloheximide revealed that about half of the nanoparticles were transported via the intestinal lymphatic transport pathway and the other half of the nanoparticles were transported via portal blood absorption. The oral pharmacological bioavailability of the nanoparticles in type I diabetic mice was 12.5-20.5%. This study demonstrates that nanoparticles are a promising oral delivery system for insulin.