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  1. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

    PubMed Central

    Dantas, Simone Alves; Ficker, Elisabeth Salvatori; Vinagre, Carmen G. C.; Ianni, Barbara Maria; Maranhão, Raul Cavalcante; Mady, Charles

    2010-01-01

    INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [3H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m2] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h−1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. PMID:20126342

  2. Novel formulation of a methotrexate derivative with a lipid nanoemulsion

    PubMed Central

    Moura, Juliana A; Valduga, Claudete J; Tavares, Elaine R; Kretzer, Iara F; Maria, Durvanei A; Maranhão, Raul C

    2011-01-01

    Background Lipid nanoemulsions that bind to low-density lipoprotein receptors can concentrate chemotherapeutic agents in tissues with low-density lipoprotein receptor overexpression and decrease the toxicity of the treatment. The aim of this study was to develop a new formulation using a lipophilic derivative of methotrexate, ie, didodecyl methotrexate (ddMTX), associated with a lipid nanoemulsion (ddMTX-LDE). Methods ddMTX was synthesized by an esterification reaction between methotrexate and dodecyl bromide. The lipid nanoemulsion was prepared by four hours of ultrasonication of a mixture of phosphatidylcholine, triolein, and cholesteryloleate. Association of ddMTX with the lipid nanoemulsion was performed by additional cosonication of ddMTX with the previously prepared lipid nanoemulsion. Formulation stability was evaluated, and cell uptake, cytotoxicity, and acute animal toxicity studies were performed. Results The yield of ddMTX incorporation was 98% and the particle size of LDE-ddMTX was 60 nm. After 48 hours of incubation with plasma, approximately 28% ddMTX was released from the lipid nanoemulsion. The formulation remained stable for at least 45 days at 4°C. Cytotoxicity of LDE-ddMTX against K562 and HL60 neoplastic cells was higher than for methotrexate (50% inhibitory concentration [IC50] 1.6 versus 18.2 mM and 0.2 versus 26 mM, respectively), and cellular uptake of LDE-ddMTX was 90-fold higher than that of methotrexate in K562 cells and 75-fold in HL60 cells. Toxicity of LDE-ddMTX, administered at escalating doses, was higher than for methotrexate (LD50 115 mg/kg versus 470 mg/kg; maximum tolerated dose 47 mg/kg versus 94 mg/kg) in mice. However, the hematological toxicity of LDE-ddMTX was lower than for methotrexate. Conclusion LDE-ddMTX was stable, and uptake of the formulation by neoplastic cells was remarkably greater than of methotrexate, which resulted in markedly greater cytotoxicity. LDE-ddMTX is thus a promising formulation to be tested in

  3. Protein-stabilized nanoemulsions and emulsions: comparison of physicochemical stability, lipid oxidation, and lipase digestibility.

    PubMed

    Lee, Sung Je; Choi, Seung Jun; Li, Yan; Decker, Eric Andrew; McClements, David Julian

    2011-01-12

    The properties of whey protein isolate (WPI) stabilized oil-in-water (O/W) nanoemulsions (d(43) ≈ 66 nm; 0.5% oil, 0.9% WPI) and emulsions (d(43) ≈ 325 nm; 0.5% oil, 0.045% WPI) were compared. Emulsions were prepared by high-pressure homogenization, while nanoemulsions were prepared by high-pressure homogenization and solvent (ethyl acetate) evaporation. The effects of pH, ionic strength (0-500 mM NaCl), thermal treatment (30-90 °C), and freezing/thawing on the stability and properties of the nanoemulsions and emulsions were compared. In general, nanoemulsions had better stability to droplet aggregation and creaming than emulsions. The nanoemulsions were unstable to droplet flocculation near the isoelectric point of WPI but remained stable at higher or lower pH values. In addition, the nanoemulsions were stable to salt addition, thermal treatment, and freezing/thawing (pH 7). Lipid oxidation was faster in nanoemulsions than emulsions, which was attributed to the increased surface area. Lipase digestibility of lipids was slower in nanoemulsions than emulsions, which was attributed to changes in interfacial structure and protein content. These results have important consequences for the design and utilization of food-grade nanoemulsions.

  4. Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis

    PubMed Central

    Mello, Suzana B V; Tavares, Elaine R; Guido, Maria Carolina; Bonfá, Eloisa; Maranhão, Raul C

    2016-01-01

    OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate. METHODS: Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with 3H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 µmol/kg methotrexate, n=7), or commercial methotrexate (0.5 µmol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis. RESULTS: The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment. CONCLUSIONS: The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were

  5. Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin

    PubMed Central

    Jiang, Sai-Ping; He, Sai-Nan; Li, Yun-Long; Feng, Da-Lin; Lu, Xiao-Yang; Du, Yong-Zhong; Yu, He-Yong; Hu, Fu-Qiang; Yuan, Hong

    2013-01-01

    Purpose Safe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed. Methods LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma) cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor. Results The LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG)2000] (DSPE-PEG 2000) does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting. Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced. Conclusion The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin. PMID:23990722

  6. A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel.

    PubMed

    Jing, Xiaolong; Deng, Li; Gao, Baoan; Xiao, Lin; Zhang, Yingying; Ke, Xingfa; Lian, Jianhao; Zhao, Qiang; Ma, Lulu; Yao, Jianzhong; Chen, Jianming

    2014-02-01

    A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug-delivery carrier for paclitaxel (PTX) was successfully developed. The formulation comprised a PEG400 solution of the drug (25mg/mL) that would be mixed with commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1mg/mL) prior to use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could significantly reduce extraction of reticuloendothelial system (RES) organs and increase tumor uptake, and exhibited more potent antitumor efficacy on bearing A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation response yet, and showed the same cytotoxicity against HeLa cells as Taxol®, and its LD50 was 2.7-fold higher than that of Taxol®, suggesting its good safety and druggability. In addition, TPLE displayed distinctly faster release of PTX, a greater proportion of PTX in phospholipids layer and a smaller share in oil phase than CPLE. From the Clinical Editor: This study demonstrates the feasibility and potential advantage of a novel PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in clinical application for the cancer therapy. This team of investigators convincingly demonstrates the feasibility and potential advantage of a PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in cancer therapy, documenting superior safety and faster release of PTX compared to commercially available formulations. © 2014.

  7. In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions: potential role of antioxidants.

    PubMed

    Courraud, J; Charnay, C; Cristol, J P; Berger, J; Avallone, S

    2013-12-01

    Over the last decades, oxidative stress has been described as a deleterious phenomenon contributing to numerous noncommunicable diseases such as cardiovascular disease, diabetes, and cancers. As many authors ascribed the healthy effect of fruit and vegetable consumption mainly to their antioxidant contents, it has been hypothesized that their protection could occur from the gut. Therefore, the aim of this study was to develop an original and physiological model of nanoemulsions to study lipid peroxidation within the intestine and to assess the properties of potential antioxidants in this setting. Several nanoemulsions were compared in terms of physical characteristics and reactivity to 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced oxidation. Formulations included different types of lipids, a detergent (a conjugated bile salt or sodium dodecyl sulfate) and, finally, lipophilic antioxidants. Hemin and myoglobin were also tested as relevant potential oxidants. Fatty acid (FA) peroxidation was monitored by gas chromatography while malondialdehyde and antioxidant contents were measured by HPLC. Investigated nanoemulsions were composed of spherical or cylindrical mixed micelles, the latter being the least resistant to oxidation. In the experimental conditions, AAPH was the only efficient oxidant. Alpha-tocopherol and lutein significantly slowed FA degradation from 4 to 1 μM, respectively. On the contrary, beta-carotene did not show any protective capacity at 4 μM. In conclusion, the tested nanoemulsions were appropriate to assess antioxidant capacity during the intestinal phase of digestion.

  8. Delivery of dietary triglycerides to Caenorhabditis elegans using lipid nanoparticles: Nanoemulsion-based delivery systems.

    PubMed

    Colmenares, Daniel; Sun, Quancai; Shen, Peiyi; Yue, Yiren; McClements, D Julian; Park, Yeonhwa

    2016-07-01

    The nematode Caenorhabditis elegans is a powerful tool for studying food bioactives on specific biochemical pathways. However, many food bioactives are highly hydrophobic with extremely low water-solubilities, thereby making them difficult to study using C. elegans. The purpose of this study was to develop nanoemulsion-based systems to deliver hydrophobic molecules in a form that could be ingested by C. elegans. Optical microscopy showed that oil-in-water nanoemulsions with a range of particle diameters (40-500nm) could be ingested by C. elegans. The amount of lipid ingested depended on the size and concentration of the nanoparticles. Fatty acid analysis showed incorporation of conjugated linoleic acid and there was a significant reduction in the fat levels of C. elegans when they were incubated with nanoemulsions containing conjugated linoleic acid, which suggested that this hydrophobic lipid was successfully delivered to the nematodes. The incorporation of hydrophobic molecules into nanoemulsion based-delivery systems may therefore enable their activities to be studied using C. elegans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery.

    PubMed

    Gönüllü, Ümit; Üner, Melike; Yener, Gülgün; Karaman, Ecem Fatma; Aydoğmuş, Zeynep

    2015-03-01

    Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p<0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin.

  10. Microencapsulation of nanoemulsions: novel Trojan particles for bioactive lipid molecule delivery

    PubMed Central

    Li, Xiang; Anton, Nicolas; Ta, Thi Minh Chau; Zhao, Minjie; Messaddeq, Nadia; Vandamme, Thierry F

    2011-01-01

    Background Nanoemulsions consist of very stable nanodroplets of oil dispersed in an aqueous phase, typically below 300 nm in size. They can be used to obtain a very fine, homogeneous dispersion of lipophilic compounds in water, thus facilitating their handling and use in nanomedicine. However, the drawback is that they are suspended in an aqueous media. This study proposes a novel technique for drying lipid nanoemulsion suspensions to create so-called Trojan particles, ie, polymer microparticles (around 2 μm) which very homogeneously “entrap” the nano-oil droplets (around 150 nm) in their core. Methods Microencapsulation of the nanoemulsions was performed using a spray-drying process and resulted in a dried powder of microparticles. By using a low-energy nanoemulsification method and relatively gentle spray-drying, the process was well suited to sensitive molecules. The model lipophilic molecule tested was vitamin E acetate, encapsulated at around 20% in dried powder. Results We showed that the presence of nanoemulsions in solution before spray-drying had a significant impact on microparticle size, distribution, and morphology. However, the process itself did not destroy the oil nanodroplets, which could easily be redispersed when the powder was put back in contact with water. High-performance liquid chromatography follow-up of the integrity of the vitamin E acetate showed that the molecules were intact throughout the process, as well as when conserved in their dried form. Conclusion This study proposes a novel technique using a spray-drying process to microencapsulate nanoemulsions. The multiscale object formed, so-called Trojan microparticles, were shown to successfully encapsulate, protect, and release the lipid nanodroplets. PMID:21760727

  11. Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

    PubMed Central

    Bertato, Marina P; Oliveira, Carolina P; Wajchenberg, Bernardo L; Lerario, Antonio C; Maranhão, Raul C

    2012-01-01

    OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and 3H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the 3H-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic

  12. P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation

    PubMed Central

    Simion, Viorel; Constantinescu, Cristina Ana; Stan, Daniela; Deleanu, Mariana; Tucureanu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Simionescu, Maya

    2016-01-01

    Inflammation is a common process associated with numerous vascular pathologies. We hypothesized that targeting the inflamed endothelium by coupling a peptide with high affinity for P-selectin to the surface of dexamethasone-loaded lipid nanoemulsions will highly increase their specific binding to activated endothelial cells (EC) and reduce the cell activation. We developed and characterized dexamethasone-loaded lipid nanoemulsions directed towards P-selectin (PLN-Dex) and monitored their anti-inflammatory effects in vitro using cultured EC (EA.hy926 cells) and in vivo using a mouse model of acute inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6 mice]. We found that PLN-Dex bound specifically to the surface of activated EC are efficiently internalized by EC and reduced the expression of proinflammatory genes, thus preventing the monocyte adhesion and transmigration to/through activated EC. Given intravenously in mice with acute inflammation, PLN-Dex accumulated at a significant high level in the lungs (compared to nontargeted nanoemulsions) and significantly reduced mRNA expression level of key proinflammatory cytokines such as IL-1β, IL-6, and MCP-1. In conclusion, the newly developed nanoformulation, PLN-Dex, is functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs' inflammation, in a mouse model of acute inflammation. PMID:27703301

  13. The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

    PubMed

    Hagigit, Tal; Nassar, Taher; Behar-Cohen, Francine; Lambert, Gregory; Benita, Simon

    2008-09-01

    Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.

  14. Enhancement of Nutraceutical Bioavailability using Excipient Nanoemulsions: Role of Lipid Digestion Products on Bioaccessibility of Carotenoids and Phenolics from Mangoes.

    PubMed

    Liu, Xuan; Bi, Jinfeng; Xiao, Hang; McClements, David Julian

    2016-03-01

    The ability of excipient nanoemulsions to increase the bioaccessibility of different kinds of nutraceuticals (phenolics and carotenoids) in mangoes was studied. Oil-in-water excipient nanoemulsions containing small digestible lipid nanoparticles (d < 200 nm) were prepared using different oil phases: medium chain triglycerides (MCT) and long-chain triglycerides (LCT). These nanoemulsions were then mixed with pureed mango and passed through a simulated gastrointestinal tract (GIT): mouth, stomach, and small intestine. Carotenoid bioaccessibility decreased in the following order: LCT nanoemulsions > MCT nanoemulsions > buffer solution, which was attributed to differences in the solubilization capacity of the mixed micelles generated in the intestinal fluids. The digestion products of LCT formed mixed micelles with hydrophobic domains large enough to accommodate the carotenoids, whereas those of MCT did not. Excipient emulsions had much less effect on phenolic bioaccessibility, which may be because phenolics are smaller more polar molecules and are therefore more easily solubilized in aqueous intestinal fluids. These results highlight the potential of excipient nanoemulsions in boosting the bioavailability of lipophilic bioactive agents in fruits and vegetables. © 2016 Institute of Food Technologists®

  15. Consequences of lipidic nanoemulsions on membrane integrity and ultrastructural morphology of Staphylococcus aureus

    NASA Astrophysics Data System (ADS)

    Singh, Neeru; Manaswita Verma, Saurabh; Singh, Sandeep Kumar; Ranjan Prasad Verma, Priya

    2014-04-01

    The present study divulges the consequences of lipidic nanoemulsions (cationized and non-cationized) on morphology and membrane integrity of Staphylococcus aureus using transmission electron microscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Transmission electron microscopic (TEM) images reveal that the cationized lipidic emulsions (CLEs) remained adhered even after the hostile treatment to remove nanoemulsions by centrifugation owing to electrostatic attraction between CLE and negatively charged bacterial surface. TEM images portray the extensive cell lyses owing to the release of cytoplasmic content when treated with both CLE and Non-CLE (NCLE). The AFM analysis of the NCLE and CLE treated S. aureus cells showed the root mean square roughness of 11.3 ± 2.8 nm and 17.7 ± 3.2 nm, respectively. The complete losses of bacterial colonies after 45 min of contact with NCLE were observed. No viable bacterial colonies were noticeable after 10 min of contact when treated with CLE, indicating better rate of killing with respect to NCLE. Similar results were obtained in the zone of inhibition studies. Significant (p < 0.05) increase of cytoplasmic material was observed both in NCLE (0.192 ± 0.003) and CLE (0.308 ± 0.012) as compared to control (0.019 ± 0.002). The present finding illustrates that the NCLE and CLE had caused significant membrane disorganization leading to release of cytoplasmic content causing irreversible cell damage, which is in accordance with the TEM, SEM and AFM studies.

  16. Influence of particle size on the in vitro and in vivo anti-inflammatory and anti-allergic activities of a curcumin lipid nanoemulsion.

    PubMed

    Onodera, Takefumi; Kuriyama, Isoko; Andoh, Tooru; Ichikawa, Hideki; Sakamoto, Yuka; Lee-Hiraiwa, Eibai; Mizushina, Yoshiyuki

    2015-06-01

    The polyphenolic compound, curcumin, is a natural yellow pigment component of turmeric. It exerts various biological effects, such as anti-inflammatory effects, and we have previously demonstrated that curcumin is a specific inhibitor of DNA polymerase λ. Curcumin is characterized by poor bioavailability as it is water-insoluble, is poorly absorbed and is systemically eliminated. In order to increase the bioavailability of curcumin, in this study, we produced a curcumin-loaded lipid nanoemulsion of various particle sizes (50, 100 and 200 nm). The curcumin lipid nanoemulsion was prepared by a modified thin-film hydration method followed by sonication. To identify the optimal particle size which exhibits the strongest physiological activity, we investigated the inhibitory effects of the obtained nanoemulsions against inflammatory and allergic activities. In in vitro cell culture experiments, the 100-nm curcumin lipid nanoemulsion showed the most prominent inhibitory effect on the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW264.7 murine macrophages, and on the release of β-hexosaminidase induced by the calcium ionophore, A23187, in rat basophilic leukemia RBL-2H3 cells. In an in vivo experiment, in which mice were administered the curcumin-loaded lipid nanoemulsion of various particle sizes, the 100-nm curcumin lipid nanoemulsion showed the most prominent anti-inflammatory and anti-allergic effects, inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema and immunoglobulin E (IgE)-induced passive cutaneous anaphylactic (PCA) reaction. The effects of particle size on serum curcumin absorption were also assessed in mice, and the 100-nm lipid nanoemulsion showed the greatest absorption. The results from our study suggest that the physiological activities of curcumin lipid nanoemulsions differ depending on particle size. Our data indicate that the curcumin lipid nanoemulsion with a particle size of 100

  17. Behavior of vitamin E acetate delivery systems under simulated gastrointestinal conditions: lipid digestion and bioaccessibility of low-energy nanoemulsions.

    PubMed

    Mayer, Sinja; Weiss, Jochen; McClements, David Julian

    2013-08-15

    Colloidal delivery systems are needed to incorporate oil-soluble vitamins into aqueous-based foods and beverage products. In this study, we encapsulated vitamin E acetate into oil-in-water nanoemulsions produced using either a low-energy method (Emulsion Phase Inversion, EPI) or a high energy method (microfluidization). Oil-in-water nanoemulsions (d<200 nm) could be produced using both low- and high-energy methods from a non-ionic surfactant (Tween 80) and medium chain triglycerides (MCTs). The influence of surfactant-to-oil ratio (SOR) on lipid digestion and vitamin bioaccessibility of EPI nanoemulsions was determined using a gastrointestinal tract (GIT) model that simulated the mouth, stomach, and small intestine. There were increases in the size and negative charge of the oil droplets after passage through the GIT, which was attributed to droplet coalescence and changes in interfacial composition. The rate and extent of lipid digestion decreased with increasing surfactant concentration, but the bioaccessibility of vitamin E acetate was high in all of the samples (>95%). No appreciable influence of the preparation method (low-energy versus high-energy) on lipid digestion and vitamin bioaccessibility was observed. The major advantage of the EPI method for forming nanoemulsions is that no expensive equipment is required, but relatively high surfactant concentrations are needed compared to microfluidization. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery.

    PubMed

    Nasr, Maha

    2016-05-01

    The development of mucoadhesive lipidic nanoemulsion based on hyaluronic acid, co-encapsulating two polyphenols (resveratrol and curcumin) for the transnasal treatment of neurodegenerative diseases was attempted in the current manuscript. Nanoemulsions were prepared by the spontaneous emulsification method, and were characterized for their particle size, zeta potential, mucoadhesive strength and morphology. The selected formula was tested for its antioxidant potential, in vitro and ex vivo release of the two polyphenols, safety on nasal mucosa and in vivo quantification of the two drugs in rat brains. Its stability was tested by monitoring the change in particle size, zeta potential, drugs' content and antioxidant potential upon storage for 3 months. The optimized hyaluronic acid based nanoemulsion formula displayed a particle size of 115.2 ± 0.15 and a zeta potential of -23.9 ± 1.7. The formula displayed a spherical morphology and significantly higher mucoadhesive strength compared to its non mucoadhesive counterpart. In addition, the nanoemulsion was able to preserve the antioxidant ability of the two polyphenols and protect them from degradation. Diffusion controlled release of the two drugs was achievable till 6 hours, with an ex vivo flux across sheep nasal mucosa of 2.86 and 2.09 µg/cm(2)hr for resveratrol and curcumin, respectively. Moreover, the mucoadhesive nanoemulsion was safe on nasal mucosa and managed to increase the amounts of the two polypehnols in the brain (about 7 and 9 folds increase in AUC0-7 h for resveratrol and curcumin, respectively). Hyaluronic acid based lipidic nanoemulsion proved itself as a successful carrier enhancing the solubility, stability and brain targetability of polyphenols.

  19. The preparation of magnetically guided lipid based nanoemulsions using self-emulsifying technology

    NASA Astrophysics Data System (ADS)

    Bakandritsos, Aristides; Zboril, Radek; Bouropoulos, Nikolaos; Kallinteri, Paraskevi; Favretto, Marco E.; Parker, Terry L.; Mullertz, Anette; Fatouros, Dimitrios G.

    2010-02-01

    This paper reports an easy and highly reproducible preparation route, using self-emulsifying technology, for an orally administered high quality magnetically responsive drug delivery system. Hydrophobic iron oxide nanoparticles of about 5 nm in diameter were prepared and incorporated into the lipid core of the produced oil droplets of a self-nanoemulsifying drug delivery system (MagC18/SNEDDS). The produced nanoemulsion exhibits colloidal stability at high ionic strengths and temperatures. The observed value of the saturation magnetization at 2 K is ≈4.1 emu g-1. The nanoemulsion displayed the magnetic properties of a non-interacting assembly of superparamagnetic particles and a low blocking temperature. Moreover the effect of MagC18/SNEDDS on biological systems in vitro was investigated in rodent fibroblasts (3T3 cells). The cytotoxicity studies show that none of the formulations tested affected cell activity significantly over the 24 h incubation. Such systems might have a potential use for oral delivery of poorly soluble compounds by extending the residence time of the formulation in the small intestine resulting in increased drug absorption values.

  20. Reverse micelle-loaded lipid nano-emulsions: new technology for nano-encapsulation of hydrophilic materials.

    PubMed

    Anton, Nicolas; Mojzisova, Halina; Porcher, Emilien; Benoit, Jean-Pierre; Saulnier, Patrick

    2010-10-15

    This study presents novel, recently patented technology for encapsulating hydrophilic species in lipid nano-emulsions. The method is based on the phase-inversion temperature method (the so-called PIT method), which follows a low-energy and solvent-free process. The nano-emulsions formed are stable for months, and exhibit droplet sizes ranging from 10 to 200 nm. Hydrophilic model molecules of fluorescein sodium salt are encapsulated in the oily core of these nano-emulsion droplets through their solubilisation in the reverse micellar system. As a result, original, multi-scaled nano-objects are generated with a 'hydrophilic molecule in a reverse-micelles-in-oil-in-water' structure. Once fluorescein has been encapsulated it remains stable, for thermodynamic reasons, and the encapsulation yields can reach 90%. The reason why such complex objects can be formed is due to the soft method used (PIT method) which allows the conservation of the structure of the reverse micelles throughout the formulation process, up to their entrapment in the nano-emulsion droplets. In this study, we focus the investigation on the process itself, revealing its potential and limits. Since the formulation of nanocarriers for the encapsulation of hydrophilic substances still remains a challenge, this study may constitute a significant advance in this field. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Mannosylated Lipid Nano-emulsions Loaded with Lycorine-oleic Acid Ionic Complex for Tumor Cell-specific Delivery

    PubMed Central

    Guo, Yangming; Liu, Xing; Sun, Xun; Zhang, Qiang; Gong, Tao; Zhang, Zhirong

    2012-01-01

    This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) . The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs). In order to increase its lipophilicity, lycorine-oleic acid ionic complex (LYC-OA) was made. M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis. The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines. The entrapment efficiency of M-LYC-OA-LNEs was 82.7 ± 1.6 %. The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs. The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs. These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer. PMID:23227126

  2. Carrier characteristics influence the kinetics of passive drug loading into lipid nanoemulsions.

    PubMed

    Göke, Katrin; Bunjes, Heike

    2017-08-11

    passive loading in nanoemulsions. Whilst the drug's characteristics - apart from drug surface area - are basically fixed, the lipid nanocarriers can be customized to improve passive loading speed, e.g. by using small nanocarrier particles. The knowledge of the loading mechanism now allows the use of passive loading for the straightforward, material-saving selection of suitable lipid drug nanocarriers. Copyright © 2017. Published by Elsevier B.V.

  3. Functional nanoemulsion-hybrid lipid nanocarriers enhance the bioavailability and anti-cancer activity of lipophilic diferuloylmethane

    NASA Astrophysics Data System (ADS)

    Sun, Lili; Wan, Kun; Hu, Xueyuan; Zhang, Yonghong; Yan, Zijun; Feng, Jiao; Zhang, Jingqing

    2016-02-01

    The purpose of this study was to assess the enhanced physicochemical characteristics, in vitro release behavior, anti-lung cancer activity, gastrointestinal absorption, in vivo bioavailability and bioequivalence of functional nanoemulsion-hybrid lipid nanocarriers containing diferuloylmethane (DNHLNs). The DNHLNs were first fabricated by loading water-in-oil nanoemulsions into hybrid lipid nanosystems using nanoemulsion-thin film-sonication dispersion technologies. The in situ absorption and in vitro and in vivo kinetic features of DNHLNs were measured using an in situ unidirectional perfusion method, a dynamic dialysis method and a plasma concentration-time profile-based method, respectively. The cytotoxic effects of DNHLNs in lung adenocarcinoma A549 cells were examined using MTT colorimetric analysis. The absorptive constants and permeabilities of DNHLNs in four gastrointestinal sections increased by 1.43-3.23 times and by 3.10-7.76 times that of diferuloylmethane (DIF), respectively. The relative bioavailability of DNHLNs to free DIF was 855.02%. DNHLNs inhibited cancer cell growth in a time- and dose-dependent manner. DNHLNs markedly improved the absorption and bioavailability of DIF after oral administration. DNHLNs had stronger inhibitory effects on the viability of A549 cells than that of free DIF. DNHLNs might be potentially promising nanocarriers for DIF delivery via the oral route to address unmet clinical needs.

  4. Plasma kinetics of an LDL-like non-protein nanoemulsion and transfer of lipids to high-density lipoprotein (HDL) in patients with rheumatoid arthritis.

    PubMed

    Pozzi, Fernanda S; Maranhão, Raul C; Guedes, Lissiane K; Borba, Eduardo F; Laurindo, Ieda M M; Bonfa, Eloisa; Vinagre, Carmen G

    2015-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with cardiovascular risk, but with normal plasma lipids. The aim was to investigate low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism in RA patients using radioactive nanoemulsions resembling an LDL lipid structure (LDE) as metabolic probes. Thirty patients with RA, 16 in remission and 14 in high activity, and 30 healthy controls were studied. LDE labeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-unesterified cholesterol ((3)H-UC) was intravenously injected followed by 24-hour plasma sampling. Fractional clearance rates (FCR, h(-1)) were calculated by compartmental analysis. Lipid transfers to HDL were assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified after chemical precipitation. LDL cholesterol, triglycerides, unesterified cholesterol, and oxidized LDL were equal in RA and controls, and HDL cholesterol was even higher in RA. Compared with controls, apolipoprotein B was lower, apolipoprotein A1 was equal, and apolipoprotein E was higher in RA. Decay curves of LDE labels were faster in RA patients than in controls ((14)C-CE: 0.072 ± 0.066 and 0.038 ± 0.027, P = .0115; (3)H-UC: 0.066 ± 0.042 and 0.035 ± 0.039; P < .0044). FCRs were equal in 2 RA subgroups. Transfer of UC, triglycerides, and phospholipids to HDL was equal between RA and controls, but CE transfer was lower in RA. HDL size was smaller in RA patients than in controls (8.5 ± 0.5 nm; 9.2 ± 0.8 nm, P < .0001). RA patients were more efficient in removing atherogenic LDL from plasma, as indicated by higher CE and UC FCR, with in lower apolipoprotein B. This was unexpected because of the higher cardiovascular risk in RA. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. Nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: effect on skin permeation.

    PubMed

    Clares, Beatriz; Calpena, Ana C; Parra, Alexander; Abrego, Guadalupe; Alvarado, Helen; Fangueiro, Joana F; Souto, Eliana B

    2014-10-01

    The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40|mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 ± 1.58 μg, 4.36 ± 0.21 μg and 3.64 ± 0.28 μg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 ± 0.12 μg/h) > LPs (0.15 ± 0.09 μg/h) > SLNs (0.10 ± 0.05 μg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.

  6. Drug delivery and drug targeting with parenteral lipid nanoemulsions - A review.

    PubMed

    Hörmann, Karl; Zimmer, Andreas

    2016-02-10

    Lipid nanosized emulsions or nanoemulsions (NE) are oil in water dispersions with an oil droplet size of about 200nm. This size of oil droplets dispersed in a continuous water phase is a prerequisite for the parenteral, namely intravenous administration. Many parenteral nutrition and drug emulsions on the market confirm the safe use of NE over years. Parenteral emulsions loaded with APIs (active pharmaceutical ingredients) are considered as drug delivery systems (DDS). DDS focuses on the regulation of the in vivo dynamics, such as absorption, distribution, metabolism, and extended bioavailability, thereby improving the effectiveness and the safety of the drugs. Using an emulsion as a DDS, or through the use of surface diversification of the dispersed oil droplets of emulsions, a targeted increase of the API concentration in some parts of the human body can be achieved. This review focuses on NE similar to the marketed once with no or only low amount of additional surfactants beside the emulsifier from a manufacturing point of view (technique, used raw materials).

  7. Rationalizing lipid nanoemulsion formation for utilization in the food and beverage industry

    NASA Astrophysics Data System (ADS)

    Rao, Jiajia

    There is growing interest in the use of nanoemulsions as delivery systems for lipophilic functional agents in food and beverage products due to their high optical clarity, physical stability and bioavailability. The goal of this research is to establish quantitative structure-function relationships to allow rational formulation of food-grade nanoemulsions for food and beverage applications. Initially, formation of oil-in-water nanoemulsions using a low energy method was examined. Nanoemulsions were formed using the phase inversion temperature (PIT) method, which involves heating a surfactant, oil, water (SOW) systems near the PIT, and then cooling rapidly with stirring. Preliminary experiments were carried out using a model system consisting of a non-ionic surfactant (C12E4), hydrocarbon oil (tetradecane), and water. Nanoemulsions were formed by holding SOW mixtures near their PIT (38.5 °C) and then cooling them rapidly to 10 °C. The PIT was measured using electrical, conductivity and turbidity methods. The optimum storage temperature for PIT-nanoemulsions was about 27 °C lower than the PIT. The stability of PIT-nanoemulsions at ambient temperatures can be improved by adding either Tween 80 (0.2 wt%) or SDS (0.1 wt%) to displace the C12E4 (Brij 30) from the nano-droplet surfaces. Experiments were then carried out to establish if stable nanoemulsions could be formed using the PIT method from food-grade ingredients. Nanoemulsions were fabricated from a non-ionic surfactant (Tween 80) and flavor oil (lemon oil) by heat treatment. Different types of colloidal dispersion could be formed by simple heat treatment (90 °C, 30 minutes) depending on the surfactant-to-oil ratio (SOR): emulsions at SOR < 1; nanoemulsions at 1 < SOR < 2; microemulsions at SOR > 2. The results suggested that there was a kinetic energy barrier in the SOW system at ambient temperature that prevented it from moving from a highly unstable system into a nanoemulsion system. The conditions where

  8. Curcumin and linseed oil co-delivered in phospholipid nanoemulsions enhances the levels of docosahexaenoic acid in serum and tissue lipids of rats.

    PubMed

    Sugasini, D; Lokesh, B R

    2017-04-01

    Docosahexaenoic acid (DHA) is an important long chain omega-3 polyunsaturated fatty acid (PUFA) primarily found in marine fishes. The diets of vegetarian population do not contain preformed DHA, but they can derive it from shorter chain α-linolenic acid (ALA) found in plant oils. However, the conversion efficiency of ALA to DHA is minimal in human adults. This may cause insufficiency of DHA in the vegetarian population. Curcumin, diferuloyl methane found in the spice turmeric, has the potential to increase the formation of DHA from ALA by activating the enzymes FADS2 and elongase 2. The present study was designed to prepare curcumin nanoemulsion using phospholipid core material (Lipoid™) and exploring the possibility of enhancing its bioavailability and its impact on DHA levels in rats. Curcumin was dissolved in coconut oil (CNO, MCFA rich), Sunflower oil (SNO, n-6 PUFA rich) or Linseed oil (LSO, n-3 PUFA rich) and nanoemulsions were prepared after mixing with Lipoid™ using high pressure homogenizer. The nanoemulsions were fed to weaning rats for 60 days along with AIN-93 diets. Rats fed nanoemulsion containing curcumin in LSO showed high levels of curcumin in serum liver, heart and brain. Significant increase in DHA levels of serum and tissue lipids were observed in rats given LSO with curcumin in nanoemulsions. Therefore, supplementation of diets with ALA rich LSO and curcumin could increase DHA concentrations in serum, liver, heart and brain lipids which have implications for meeting the DHA requirements of vegetarian populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Acid-sensitive lipidated doxorubicin prodrug entrapped in nanoemulsion impairs lung tumor metastasis in a breast cancer model.

    PubMed

    Dos Santos Câmara, Ana Lygia; Nagel, Gregor; Tschiche, Harald R; Cardador, Camila Magalhães; Muehlmann, Luis Alexandre; de Oliveira, Daniela Mara; Alvim, Paula Queiroz; Azevedo, Ricardo Bentes; Calderón, Marcelo; Figueiró Longo, João Paulo

    2017-08-01

    To develop an acid-sensitive lipidated, doxorubicin (Dox) prodrug (C16-Dox) to be entrapped in lipid nanoemulsion (NE-C16-Dox) as a nanocarrier to treat breast cancer models (in vitro and in vivo). We report the efficacy of NE-C16-Dox in in vitro experiments, as well as the improved chemotherapeutic index and tumor-control efficacy compared with treatment with free Dox in an in vivo murine 4T1 breast cancer model. In addition, NE-C16-Dox allowed the use of a higher dose of Dox, acceptable biocompatibility and a significant reduction in lung metastasis. Taken together, these results indicate that NE-C16-Dox is promising for breast cancer treatment, thus creating possibilities to translate these nanotechnology concepts to clinical applications.

  10. Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein

    PubMed Central

    Argenta, Débora Fretes; de Mattos, Cristiane Bastos; Misturini, Fabíola Dallarosa; Koester, Leticia Scherer; Bassani, Valquiria Linck; Simões, Cláudia Maria Oliveira; Teixeira, Helder Ferreira

    2014-01-01

    The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil), phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC]), and ionic cosurfactant type (oleic acid or oleylamine) as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV) and genistein content close to 100% (at 1 mg/mL). The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS) and herpes simplex virus 22 (strain 333). Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising options in herpes treatment. PMID:25336951

  11. A New Application of Lipid Nanoemulsions as Coating Agent, Providing Zero-Order Hydrophilic Drug Release from Tablets

    PubMed Central

    Anton, Nicolas; de Crevoisier, Astrid; Schmitt, Sabrina; Vandamme, Thierry

    2012-01-01

    The objective of the present investigation was to evaluate potential of nanoemulsions as a coating material for the tablets. The nanoemulsion of size less than 100 nm was prepared using a simple and low-energy spontaneous emulsification method. Conventional tablets containing theophylline as a model hydrophilic drug were prepared. The theophylline tablets were coated with the nanoemulsion using a fluid bed coater. The effect of different levels of the nanoemulsion coating on the theophylline release was evaluated. The theophylline tablets containing different levels of the nanoemulsion coating could be successfully prepared. Interestingly, the coating of tablet with the nanoemulsion resulted in zero-order release of theophylline from the tablets. The noncoated theophylline tablets release the entire drug in less than 2 minutes, whereas nanoemulsion coating delayed the release of theophylline from tablets. This investigation establishes the proof of concept for the potential of nanoemulsions as a coating material for tablets. PMID:22272376

  12. Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

    PubMed Central

    Kretzer, Iara F; Maria, Durvanei A; Guido, Maria C; Contente, Thaís C; Maranhão, Raul C

    2016-01-01

    Purpose Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 μmol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX. PMID:27022257

  13. Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

    PubMed

    Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

    2015-11-15

    The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ≈ fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ≈ fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility.

  14. Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma.

    PubMed

    Liu, Ying; Yu, Xue-Min; Sun, Rui-Jie; Pan, Xin-Liang

    2017-05-01

    Aim of the investigation was to develop folate-functionalized lipid nanoemulsion (LNE) comprising chemo-radiotherapeutics for targeted delivery to nasopharyngeal carcinoma (NPC). Soy lecithin nanoemulsion of doxorubicin (Dox) and yittrium-90 (90Y) was prepared by nanoprecipitation using ultrasonic homogenization technique followed by folic acid conjugation. Nanoemulsion (Dox-LNE) was characterized as positively charged (zeta potential), spherical shape (transmission electron microscopy) nano-droplets of uniform size distribution (polydispersity index). No significant variation in parameters such as particle size, zeta potential, and polydispersity index was observed when the stability of Dox-LNE was assessed during long-term storage at room temperature and at 8000 rpm, 121°C temperature, and 5000 time dilution in water. In vitro release of Dox from Dox-LNE was observed to be controlled for at least 48 h. Folate decoration over Dox-LNE surface (FD-Dox-LNE) and incorporation of 90Y in FD-Dox-LNE (FD-Dox + 90Y-LNE) changed droplet size up to 50 nm; however, surface charge of Dox-LNE did not change significantly. FD-Dox + 90Y-LNE inhibited growth of cancerous cell line like CNE1 (folate receptor rich) in vitro and alleviated tumor volume in NPC-induced nude mice significantly as compared to Dox + 90Y-LNE. Massive necrosis and hemorrhage of CNE1 cells were observed by FD-Dox + 90Y-LNE (89.9%); however, inhibition of growth of nasal epithelial cells (RPMI 2650; folate deficient) by FD-Dox + 90Y-LNE and Dox + 90Y-LNE was observed to be 21.5 and 43.65%, respectively. The investigation highlights the vast utility of folate-decorated lipid emulsion in delivering chemo-radiotherapeutics to the specific NPC site. FD-Dox + 90Y-LNE might offer a cost-effective, safe, efficacious, and clinically pertinent option to the available therapeutics.

  15. Formulation, Characterisation, and in Vitro Skin Diffusion of Nanostructured Lipid Carriers for Deoxyarbutin Compared to a Nanoemulsion and Conventional Cream

    PubMed Central

    Tofani, Rendra P.; Sumirtapura, Yeyet C.; Darijanto, Sasanti T.

    2016-01-01

    The long-term use of topical hydroquinone as an anti-hyperpigmentation treatment has well-known, unwanted effects. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl)oxy]phenol) is a relatively new tyrosinase inhibitor, with stronger inhibitory potency than hydroquinone, that exhibited decreased cytotoxicity against melanocytes and other cells. This study developed novel nanostructured lipid carriers (NLCs) for improved topical delivery of deoxyarbutin (dArb), leading to improved depigmenting efficacy. dArb is a hydrophobic substance, but it easily degrades in aqueous medium and is thermolabile. Screening and optimisation of the solid lipid, liquid lipid, surfactant, co-surfactant and production methods were performed to choose the optimum particle size and stability for NLCs. One percent dArb NLCs were obtained from a combination of cetyl palmitate (CP) and caprylic/capric tryglicerides (Myr) in 12% total lipids using poloxamer 188 (P-188) and polyethylene glycol (PEG) 400 as a surfactant and co-surfactant, respectively, with a particle diameter of approximately 500 nm and a polydispersity index (PI) <0.4. These NLCs were produced using the simple method of high-shear homogenisation (10,000 rpm, 5 minutes) and ultrasonication (3.5 min). The compatibility between the substances in the formula was evaluated using Fourier Transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The morphology of the NLCs was observed using transmission electron microscopy (TEM). In vitro penetration of dArb NLCs was evaluated and compared to the nanoemulsion (NE) and conventional emulsion (CR) delivery methods across Spangler’s membrane (SS). Delivery improvement was clearly observed, and after 8 h of application, dArb gel-NLCs showed the highest dArb penetration, followed by liquid NLCs, NE, and CR.

  16. Retinyl Ester Storage Particles (Retinosomes) from the Retinal Pigmented Epithelium Resemble Lipid Droplets in Other Tissues*

    PubMed Central

    Orban, Tivadar; Palczewska, Grazyna; Palczewski, Krzysztof

    2011-01-01

    Levels of many hydrophobic cellular substances are tightly regulated because of their potential cytotoxicity. These compounds tend to self-aggregate in cytoplasmic storage depots termed lipid droplets/bodies that have well defined structures that contain additional components, including cholesterol and various proteins. Hydrophobic substances in these structures become mobilized in a specific and regulated manner as dictated by cellular requirements. Retinal pigmented epithelial cells in the eye produce retinyl ester-containing lipid droplets named retinosomes. These esters are mobilized to replenish the visual chromophore, 11-cis-retinal, and their storage ensures proper visual function despite fluctuations in dietary vitamin A intake. But it remains unclear whether retinosomes are structures specific to the eye or similar to lipid droplets in other organs/tissues that contain substances other than retinyl esters. Thus, we initially investigated the production of these lipid droplets in experimental cell lines expressing lecithin:retinol acyltransferase, a key enzyme involved in formation of retinyl ester-containing retinosomes from all-trans-retinol. We found that retinosomes and oleate-derived lipid droplets form and co-localize concomitantly, indicating their intrinsic structural similarities. Next, we isolated native retinosomes from bovine retinal pigmented epithelium and found that their protein and hydrophobic small molecular constituents were similar to those of lipid droplets reported for other experimental cell lines and tissues. These unexpected findings suggest a common mechanism for lipid droplet formation that exhibits broad chemical specificity for the hydrophobic substances being stored. PMID:21454509

  17. Lipid dependence of diadinoxanthin solubilization and de-epoxidation in artificial membrane systems resembling the lipid composition of the natural thylakoid membrane.

    PubMed

    Goss, Reimund; Latowski, Dariusz; Grzyb, Joanna; Vieler, Astrid; Lohr, Martin; Wilhelm, Christian; Strzalka, Kazimierz

    2007-01-01

    In the present study, the solubility and enzymatic de-epoxidation of diadinoxanthin (Ddx) was investigated in three different artificial membrane systems: (1) Unilamellar liposomes composed of different concentrations of the bilayer forming lipid phosphatidylcholine (PC) and the inverted hexagonal phase (H(II) phase) forming lipid monogalactosyldiacylglycerol (MGDG), (2) liposomes composed of PC and the H(II) phase forming lipid phosphatidylethanolamine (PE), and (3) an artificial membrane system composed of digalactosyldiacylglycerol (DGDG) and MGDG, which resembles the lipid composition of the natural thylakoid membrane. Our results show that Ddx de-epoxidation strongly depends on the concentration of the inverted hexagonal phase forming lipids MGDG or PE in the liposomes composed of PC or DGDG, thus indicating that the presence of inverted hexagonal structures is essential for Ddx de-epoxidation. The difference observed for the solubilization of Ddx in H(II) phase forming lipids compared with bilayer forming lipids indicates that Ddx is not equally distributed in the liposomes composed of different concentrations of bilayer versus non-bilayer lipids. In artificial membranes with a high percentage of bilayer lipids, a large part of Ddx is located in the membrane bilayer. In membranes composed of equal proportions of bilayer and H(II) phase forming lipids, the majority of the Ddx molecules is located in the inverted hexagonal structures. The significance of the pigment distribution and the three-dimensional structure of the H(II) phase for the de-epoxidation reaction is discussed, and a possible scenario for the lipid dependence of Ddx (and violaxanthin) de-epoxidation in the native thylakoid membrane is proposed.

  18. Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids.

    PubMed

    Hinger, Doris; Navarro, Fabrice; Käch, Andres; Thomann, Jean-Sébastien; Mittler, Frédérique; Couffin, Anne-Claude; Maake, Caroline

    2016-09-07

    Photosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, however, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. However, many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics. Recently, we have designed a novel lipid nanostructured carrier, namely Lipidots, consisting of nontoxic and FDA approved ingredients as promising vehicle for the approved photosensitizer m-tetrahydroxyphenylchlorin (mTHPC). In this study we tested Lipidots of two different sizes (50 and 120 nm) and assessed their photodynamic potential in 3-dimensional multicellular cancer spheroids. Microscopically, the intracellular accumulation kinetics of mTHPC were retarded after encapsulation. However, after activation mTHPC entrapped into 50 nm particles destroyed cancer spheroids as efficiently as the free drug. Cell death and gene expression studies provide evidence that encapsulation may lead to different cell killing modes in PDT. Since ATP viability assays showed that the carriers were nontoxic and that encapsulation reduced dark toxicity of mTHPC we conclude that our 50 nm photosensitizer carriers may be beneficial for clinical PDT applications.

  19. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    PubMed Central

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  20. Influence of emulsifier structure on lipid bioaccessibility in oil-water nanoemulsions.

    PubMed

    Speranza, A; Corradini, M G; Hartman, T G; Ribnicky, D; Oren, A; Rogers, M A

    2013-07-03

    The influence of several nonionic surfactants (Tween-20, Tween-40, Tween-60, Span-20, Span-60, or Span-80) and anionic surfactants (sodium lauryl sulfate, sodium stearoyl lactylate, and sodium stearyl fumarate) showed drastic differences in the rank order of lipase activity/lipid bioaccessibility. The biophysical composition of the oil and water interface has a clear impact on the bioaccessibility of fatty acids (FA) by altering the interactions of lipase at the oil-water interface. It was found that the bioaccessibility was positively correlated with the hydrophilic/lipophilic balance (HLB) of the surfactant and inversely correlated to the surfactant aliphatic chain length. Furthermore, the induction time in the jejunum increased as the HLB value increased and decreased with increasing aliphatic chain length. The rate of lipolysis slowed in the jejunum with increasing HLB and with increasing aliphatic chain length.

  1. Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

    PubMed

    Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

    2016-09-01

    The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

  2. Conjugation of curcumin-loaded lipid nanoemulsions with cell-penetrating peptides increases their cellular uptake and enhances the anti-inflammatory effects in endothelial cells.

    PubMed

    Simion, Viorel; Stan, Daniela; Constantinescu, Cristina Ana; Deleanu, Mariana; Dragan, Emanuel; Tucureanu, Monica Madalina; Gan, Ana-Maria; Butoi, Elena; Constantin, Alina; Manduteanu, Ileana; Simionescu, Maya; Calin, Manuela

    2016-02-01

    To prepare and characterize in vitro and in vivo lipid nanoemulsions (LN) loaded with curcumin (Cm) and functionalized with a cell-penetrating peptide. Curcumin-loaded lipid nanoemulsions (CmLN) functionalized with a nona-arginine peptide (R9-CmLN) have been obtained, characterized and optimized for size, entrapment efficiency and in vitro Cm release. The interaction of R9-CmLN with human endothelial cells (HEC) was investigated using cultured EA.hy926 cells, and in vivo biodistribution studies were performed using C57BL6 mice. When used in therapeutically relevant concentration, R9-CmLN have low haemolytic activity, low cytotoxicity on HEC, and show anti-inflammatory effects by reducing the monocytes adhesion to TNF-α activated HEC. Moreover, HEC uptake and internalization of R9-CmLN was significantly higher compared to the non-functionalized CmLN. In vivo biodistribution studies in mice revealed a higher accumulation of R9-CmLN in the liver and the lungs compared to CmLN and the body clearance of the both nanoformulations after 72 h. Cell-penetrating peptides-functionalized CmLN have superior characteristics compared to their non-functionalized counterparts: are more efficiently internalized by the cells, produces anti-inflammatory effects in HEC and when administrated intravenously in mice exhibit increased accumulation in the liver and the lungs, suggesting their potential therapeutic applications in different inflammatory pathologies localized in the liver or the lungs. © 2016 Royal Pharmaceutical Society.

  3. Stability of parenteral nanoemulsions loaded with paclitaxel: the influence of lipid phase composition, drug concentration and storage temperature.

    PubMed

    Kadam, Alisha N; Najlah, Mohammad; Wan, Ka-Wai; Ahmed, Waqar; Crean, St John; Phoenix, David A; Taylor, Kevin M G; Elhissi, Abdelbary M A

    2014-12-01

    Paclitaxel was loaded into licensed parenteral nutrition nanoemulsions (Clinoleic® and Intralipid®) using bath sonication, and the stability of the formulations was investigated following storage for two weeks at room temperature or at 4 °C. In general, Clinoleic droplets were smaller than Intralipid droplets, being around 255 and 285 nm, respectively, for blank and freshly loaded emulsions. Regardless of storage temperature, the Clinoleic exhibited a very slight or no increase in droplet size upon storage, whilst the droplet size of the Intralipid emulsion increased significantly. The droplet size of both emulsions was minimally affected by paclitaxel concentration within the range of 0, 1, 3 and 6 mg/ml. The pH of both emulsions markedly decreased upon storage at room temperature, which was possibly attributed to the production of fatty acids resulting from phospholipid hydrolysis. However, at 4 °C, the pH of Clinoleic emulsion was unaffected by storage or paclitaxel concentration while the Intralipid emulsion demonstrated a trend for pH reduction. Both nanoemulsions had a negative zeta potential, with the Clinoleic formulations having the highest charge, possibly explaining the better size stability of this emulsion. Overall, this study has shown that paclitaxel was successfully loaded into clinically licensed parenteral emulsions and that Clinoleic showed greater stability than the Intralipid.

  4. Preparation and characterization of a new lipid nano-emulsion containing two cosurfactants, sodium palmitate for droplet size reduction and sucrose palmitate for stability enhancement.

    PubMed

    Takegami, Shigehiko; Kitamura, Keisuke; Kawada, Hiroto; Matsumoto, Yu; Kitade, Tatsuya; Ishida, Hiroharu; Nagata, Chieyo

    2008-08-01

    A new lipid nano-emulsion (LNE) was prepared from soybean oil and phosphatidylcholine (PC) employing two cosurfactants, sodium palmitate (PA) for reduced droplet size and sucrose palmitate (SP) for stability enhancement. The mean droplet size of LNEs prepared at a PA/PC (w/w) ratio of larger than 1/10 was found to be ca. 50 nm by dynamic light scattering and atomic force microscopy. However, during the 12-month storage, the PA/PC (1/10)-LNE showed an increase in mean droplet size and broadening of the droplet size distribution due to coalescence of the LNE particles. In a saline solution, the coalescence proceeded very rapidly, i.e., the mean droplet size increased to more than 150 nm within 0.5 h. To suppress the coalescence of LNE particles, four sucrose fatty acid esters of different chain lengths were examined as candidate cosurfactants. The results showed that PA/SP/PC (1/4/10)-LNE could maintain a mean droplet size around 50 nm for 12 months. In a saline solution, the mean droplet size could be maintained within 100 nm even after 24 h. Slight formation of flocculation in the LNEs depending on the storage period was suggested by measurement of the 31P nuclear magnetic resonance line width of the LNEs.

  5. Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies.

    PubMed

    Puglia, Carmelo; Damiani, Elisabetta; Offerta, Alessia; Rizza, Luisa; Tirendi, Giorgia Giusy; Tarico, Maria Stella; Curreri, Sergio; Bonina, Francesco; Perrotta, Rosario Emanuele

    2014-01-23

    The increased awareness of protection against UV radiation damages has led to a rise in the use of topically applied chemical sunscreen agents and to an increased need of innovative carriers designed to achieve the highest protective effect and reduce the toxicological risk resulting from the percutaneous absorption of these substances. In this paper, nanostructured lipid carriers (NLC) and nanoemulsions (NE) were formulated to optimize the topical application of different and widespread UVA or UVB sun filters (ethyl hexyltriazone (EHT), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bemotrizinol (Tinosorb S), octylmethoxycinnamate (OMC) and avobenzone (AVO)). The preparation and stability parameters of these nanocarriers have been investigated concerning particle size and zeta potential. The release pattern of the sunscreens from NLC and NE was evaluated in vitro, determining their percutaneous absorption through excised human skin. Additional in vitro studies were performed in order to evaluate, after UVA radiation treatment, the spectral stability of the sunfilters once formulated in NLC or NE. From the results obtained, when incorporated in NLC, the skin permeation abilities of the sun filter were drastically reduced, remaining mainly on the surface of the skin. The photostability studies showed that EHT, DHHB and Tinosorb S still retain their photostability when incorporated in these carriers, while OMC and AVO were not photostable as expected. However, no significant differences in terms of photoprotective efficacy between the two carriers were observed. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Nanoemulsion: for improved oral delivery of repaglinide.

    PubMed

    Akhtar, Juber; Siddiqui, Hefazat Hussain; Fareed, Sheeba; Badruddeen; Khalid, Mohammad; Aqil, Mohammed

    2016-07-01

    Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic β-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months.

  7. Size fractionation and size characterization of nanoemulsions of lipid droplets and large unilamellar lipid vesicles by asymmetric-flow field-flow fractionation/multi-angle light scattering and dynamic light scattering.

    PubMed

    Vezočnik, Valerija; Rebolj, Katja; Sitar, Simona; Ota, Katja; Tušek-Žnidarič, Magda; Štrus, Jasna; Sepčić, Kristina; Pahovnik, David; Maček, Peter; Žagar, Ema

    2015-10-30

    Asymmetric-flow field-flow fractionation technique coupled to a multi-angle light-scattering detector (AF4-MALS) was used together with dynamic light-scattering (DLS) in batch mode and transmission electron microscopy (TEM) to study the size characteristics of the trioleoylglycerol lipid droplets covered by a monolayer of sphingomyelin and cholesterol, in water phase. These lipid droplet nanoemulsions (LD) were formed by ultrasonication. In parallel, the size characteristics of large unilamellar lipid vesicles (LUV) prepared by extrusion and composed of sphingomyelin and cholesterol were determined. LD and LUV were prepared at two different molar ratios (1/1, 4/1) of sphingomyelin and cholesterol. In AF4-MALS, various cross-flow conditions and mobile phase compositions were tested to optimize the separation of LD or LUV particles. The particle radii, R, as well as the root-mean-square radii, Rrms, of LD and LUV were determined by AF4-MALS, whereas the hydrodynamic radii, Rh, were obtained by DLS. TEM visualization revealed round shape particles of LD and LUV.

  8. Use of combined chemotherapy with etoposide and methotrexate, both associated to lipid nanoemulsions for atherosclerosis treatment in cholesterol-fed rabbits.

    PubMed

    Leite, Antonio C A; Solano, Tatiana V; Tavares, Elaine R; Maranhão, Raul C

    2015-02-01

    Treatment of atherosclerotic rabbits with intravenous methotrexate or etoposide carried in lipid nanoemulsions (LDE) markedly reduced the lesions in the aorta. Here, the combined treatment with LDE-methotrexate and LDE-etoposide was investigated aiming to increase the anti-atherosclerosis effect. Thirty-six male rabbits received a diet with 1 % cholesterol for 2 months. After the first month, the animals received 4 weekly intravenous injections of LDE-methotrexate (4 mg/kg dose), LDE-etoposide (6 mg/kg), or a combination of those two drugs, while the control animals were injected with LDE (n = 9 for each group). LDE-methotrexate+LDE-etoposide reduced aortic lesion areas by 95 % compared with controls and the intima-media ratio was reduced five-fold, whereas LDE-methotrexate reduced the lesions by 81 % and LDE-etoposide by 83 %. Compared to controls, the positive area of macrophages and MMP-9 in the arterial intima was significantly reduced in all treated groups (p < 0.001), but the MMP9 reduction was greater with the combined chemotherapy than the reduction achieved by the isolated treatments. Presence of CD3 positive cells was equal in controls and LDE-methotrexate+LDE-etoposide treated animals. However, FOXP3 positive T lymphocytes in the intima were increased in the LDE-methotrexate+LDE-etoposide rabbits. Weight, food intake evolution and the hematologic parameters suggested that the treatment had very low toxicity. Compared to the single treatments with LDE-methotrexate and LDE-etoposide, the combined treatment was more effective in reducing the atherosclerotic lesions. Because the toxicity of the novel drug-target combined scheme was low, those results favor the possibility of future clinical studies in patients with cardiovascular disease.

  9. Physical properties and antimicrobial efficacy of thyme oil nanoemulsions: influence of ripening inhibitors.

    PubMed

    Chang, Yuhua; McLandsborough, Lynne; McClements, David Julian

    2012-12-05

    Thyme oil-in-water nanoemulsions (pH 3.5) were prepared as potential antimicrobial delivery systems. The nanoemulsions were highly unstable to droplet growth and phase separation, which was attributed to Ostwald ripening due to the relatively high water solubility of thyme oil. Ostwald ripening could be inhibited by mixing thyme oil with a water-insoluble ripening inhibitor (≥60 wt % corn oil or ≥50 wt % MCT in the lipid phase) before homogenization, yielding nanoemulsions with good physical stability. Physically stable thyme oil nanoemulsions were examined for their antimicrobial activities against an acid-resistant spoilage yeast, Zygosaccharomyces bailii (ZB). Oil phase composition (ripening inhibitor type and concentration) had an appreciable influence on the antimicrobial activity of the thyme oil nanoemulsions. In general, increasing the ripening inhibitor levels in the lipid phase reduced the antimicrobial efficacy of nanoemulsions. For example, for nanoemulsions containing 60 wt % corn oil in the lipid phase, the minimum inhibitory concentration (MIC) of thyme oil to inhibit ZB growth was 375 μg/mL, while for nanoemulsions containing 90 wt % corn oil in the lipid phase, even 6000 μg/mL thyme oil could not inhibit ZB growth. This effect is also dependent on ripening inhibitor types: at the same concentration in the lipid phase, MCT decreased the antimicrobial efficacy of thyme oil more than corn oil. For instance, when the level of ripening inhibitor in the lipid phase was 70 wt %, the MICs of thyme oil for nanoemulsions containing corn oil and MCT were 750 and 3000 μg/mL, respectively. The results of this study have important implications for the design and utilization of nanoemulsions as antimicrobial delivery systems in the food and other industries.

  10. Biosynthetic mechanism for L-Gulose in main polar lipids of Thermoplasma acidophilum and possible resemblance to plant ascorbic acid biosynthesis.

    PubMed

    Yamauchi, Noriaki; Nakayama, Yusuke

    2013-01-01

    L-Gulose is a very rare sugar, but appears as a sugar component of the main polar lipids characteristic in such a thermophilic archaeon as Thermoplasma acidophilum that lives without cell walls in a highly acidic environment. The biosynthesis of L-gulose in this thermophilic organism was investigated with deuterium-labeling experiments. L-Gulose was found to be biosynthesized from D-glucose via stepwise stereochemical inversion at C-2 and C-5. The involvement of an epimerase related to GDP-mannose 3,5-epimerase, the key enzyme of plant ascorbate biosynthesis, was also suggested in this C-5 inversion. The resemblance of L-gulose biosynthesis in archaea and plants might be suggested from these results.

  11. Modification of composition of a nanoemulsion with different cholesteryl ester molecular species: Effects on stability, peroxidation, and cell uptake

    PubMed Central

    Almeida, Cristina P; Vital, Carolina G; Contente, Thais C; Maria, Durvanei A; Maranhão, Raul C

    2010-01-01

    Purpose: Use of lipid nanoemulsions as carriers of drugs for therapeutic or diagnostic purposes has been increasingly studied. Here, it was tested whether modifications of core particle constitution could affect the characteristics and biologic properties of lipid nanoemulsions. Methods: Three nanoemulsions were prepared using cholesteryl oleate, cholesteryl stearate, or cholesteryl linoleate as main core constituents. Particle size, stability, pH, peroxidation of the nanoemulsions, and cell survival and uptake by different cell lines were evaluated. Results: It was shown that cholesteryl stearate nanoemulsions had the greatest particle size and all three nanoemulsions were stable during the 237-day observation period. The pH of the three nanoemulsion preparations tended to decrease over time, but the decrease in pH of cholesteryl stearate was smaller than that of cholesteryl oleate and cholesteryl linoleate. Lipoperoxidation was greater in cholesteryl linoleate than in cholesteryl oleate and cholesteryl stearate. After four hours’ incubation of human umbilical vein endothelial cells (HUVEC) with nanoemulsions, peroxidation was minimal in the presence of cholesteryl oleate and more pronounced with cholesteryl linoleate and cholesteryl stearate. In contrast, macrophage incubates showed the highest peroxidation rates with cholesteryl oleate. Cholesteryl linoleate induced the highest cell peroxidation rates, except in macrophages. Uptake of cholesteryl oleate nanoemulsion by HUVEC and fibroblasts was greater than that of cholesteryl linoleate and cholesteryl stearate. Uptake of the three nanoemulsions by monocytes was equal. Uptake of cholesteryl oleate and cholesteryl linoleate by macrophages was negligible, but macrophage uptake of cholesteryl stearate was higher. In H292 tumor cells, cholesteryl oleate showed the highest uptakes. HUVEC showed higher survival rates when incubated with cholesteryl stearate and smaller survival with cholesteryl linoleate. H292

  12. Albumin-Conjugated Lipid-Based Multilayered Nanoemulsion Improves Drug Specificity and Anti-Inflammatory Potential at the Spinal Cord Injury gSite after Intravenous Administration.

    PubMed

    Chen, Xiao-Gang; Hua, Fu; Wang, Shou-Guo; Tang, Hong-Hui

    2017-09-05

    Albumin-conjugated multilayered nanoemulsion (albumin-MNE) of methyl prednisolone (MP) was developed to ensure the specificity of the drug at the spinal cord injury (SCI) site. MNE was prepared by emulsification followed by ionic deposition of oppositely charged polymer followed by albumin conjugation using N-hydroxysuccinimide. Prepared nanoemulsion was characterized for particle size, polydispersity index (PDI), zeta potential (Zp), pH, viscosity, and entrapment efficiency. It was further evaluated for shape and morphological analysis, in vitro release, cell viability, and in vivo efficacy against post SCI-like conditions in terms of behavioral assessment, histopathological evaluation, and immunoflorescence assay of the histological sections showing Bax-driven apoptosis. Entrapment efficiency, particle size, PDI, and Zp of spherical-shaped, smooth-surfaced MNE droplets were found to be 68.9%, 83.2 ± 14.4 nm, 0.231, and + 62.7 mV, respectively. In vitro release of MP from MNE and albumin-MNE was observed to be 68.5 and 72.2% after 96th hour of the study. MNE showed higher viability of astrocytes than MP solution. Albumin-MNE improved behavior of SCI rat and histopathological conditions in a very effective manner when compared with MNE. Immunoflorescence assay reveals explicit decline in mitochondrial-mediated apoptosis by sub-cellular upregulation of Bax at spinal cord injury site. In conclusion, albumin-MNE delivered MP specifically at SCI site and avoided its instant availability inside astrocytes culture. On account of which the chitosan stabilized, lecithin-emulsified, multilayered nanoemulsion of MP depicts higher efficacy and safety than MNE and may offer safe and effective mean for the treatment of post SCI-like conditions in human.

  13. (19)F Nuclear Magnetic Resonance Spectrometric Determination of the Partition Coefficients of Flutamide and Nilutamide (Antiprostate Cancer Drugs) in a Lipid Nano-Emulsion and Prediction of Its Encapsulation Efficiency for the Drugs.

    PubMed

    Takegami, Shigehiko; Kitamura, Keisuke; Ohsugi, Mayuko; Konishi, Atsuko; Kitade, Tatsuya

    2016-12-01

    To design a useful lipid drug carrier having a high encapsulation efficiency (EE%) for the antiprostate cancer drugs flutamide (FT) and nilutamide (NT), a lipid nano-emulsion (LNE) was prepared with soybean oil (SO), phosphatidylcholine (PC), and sodium palmitate, and the partition coefficients (K ps) of the drugs for the LNE were determined by (19)F nuclear magnetic resonance (NMR) spectrometry. The (19)F NMR signal of the trifluoromethyl group of both drugs showed a downfield shift from an internal standard (trifluoroethanol) and broadening according to the increase in the lipid concentration due to their interaction with LNE particles. The difference in the chemical shift (Δδ) of each drug caused by the addition of LNE was measured under different amounts of LNE, and the K p values were calculated from the Δδ values. The results showed that FT has higher lipophilicity than NT. The total lipid concentration (SO + PC) required to encapsulate each drug into LNE with an EE% of more than 95% was calculated from the K p values as 93.3 and 189.9 mmol/L for FT and NT, respectively. For an LNE prepared with the total lipid concentration of 215 mmol/L, the predicted EE% values were 98 and 96% for FT and NT, respectively, while the experimental EE% values determined by a centrifugation method were approximately 99% for both drugs. Thus, the (19)F NMR spectrometric method is a useful technique to obtain the K p values of fluorinated drugs and thereby predict the theoretical lipid concentrations and prepare LNEs with high EE% values.

  14. Formation of transparent solid lipid nanoparticles by microfluidization: influence of lipid physical state on appearance.

    PubMed

    Helgason, Thrandur; Salminen, Hanna; Kristbergsson, Kristberg; McClements, David Julian; Weiss, Jochen

    2015-06-15

    This study investigated the influence of liquid-solid transition and particle size on the optical properties of nanoemulsions. The hypothesis was that the crystallization of lipid droplets influences the nanoemulsion appearance. Liquid and solid nanoemulsions (10 wt% octadecane, 1-5 wt% sodium dodecylsulfate) were formed by high-pressure microfluidization (5000-28,500 psi) at 45 °C. Solid lipid nanoparticles were formed by cooling the nanoemulsions to 5 °C and then heating to ambient temperature, whereas liquid nanoemulsions were formed by maintaining them at 25 °C. Results indicated that lipid nanoparticles ranging from 136 nm down to 36 nm were generated, and were stable to particle aggregation. The melting and onset temperatures of the nanoparticles decreased with decreasing particle diameter. Upon crystallization of the lipid, the absorbance increased by about 140% for nanoemulsions with 136 nm particle diameter, but only 5% for nanoemulsions with 36 nm particle diameter. These results were explained in terms of changes in refractive index upon droplet solidification that alter their scattering behavior. These results show that solidification of nanoemulsions results in a shift of the transparent-to-turbid transition regime. The practical consequences for emulsion manufacturers are that solid nanoemulsions must be smaller than liquid nanoemulsions to remain transparent. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Challenges and Future Prospects of Nanoemulsion as a Drug Delivery System.

    PubMed

    Yukuyama, Megumi Nishitani; Kato, Edna Tomiko Myiake; Lobenberg, Raimar; Bou-Chacra, Nadia Araci

    2017-01-01

    Nanoemulsion has the potential to overcome several disadvantages in drug formulation. Loading poor water-soluble drugs in the appropriate nanoemulsions enhances their wettability and/or solubility. Consequently, this improves their pharmacokinetics and pharmacodynamics by different routes of administration. Associated with the optimum nanodroplets size or even combined with key components, the droplets act as a reservoir of drugs, enabling nanoemulsion to be multifunctional platform to treat diverse diseases. A number of important advantages, which comprise nanoemulsion attributes, such as efficient drug release with appropriate rate, prolonged efficacy, drug uptake control, low side effects and drug protection properties from enzymatic or oxidative processes, have been reported in last decade. The high flexibility of nanoemulsion includes also a variety of manufacturing process options and a combination of widely assorted components such as surfactants, liquid lipids or even drug-conjugates. These features provide alternatives for designing innovative nanoemulsions aiming at high-value applications. This review presents the challenges and prospects of different nanoemulsion types and its application. The drug interaction with the components of the formulation, as well as the drug mechanistic interaction with the biological environment of different routes of administration are also presented. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Temperature and pH sensitivity of a stabilized self-nanoemulsion formed using an ionizable lipid-like material via an oil-to-surfactant transition.

    PubMed

    Tanaka, Hiroki; Oasa, Sho; Kinjo, Masataka; Tange, Kota; Nakai, Yuta; Harashima, Hideyoshi; Akita, Hidetaka

    2017-03-01

    Lipids functionalized with tertiary amines (ionizable lipids) for a pH-dependent positive charge have been developed extensively as a carrier material for delivering nucleic acids. We previously developed an SS-cleavable proton-activated lipid-like material (ssPalm) as a component of a functionalized lipid envelope structure of a nanoparticle that encapsulated plasmid DNA and short interfering RNA. In this study, we report on the unique characteristics of such an ionizable lipid: the formation of a nano-sized emulsion (ave. 40nm) via pH-triggered self-emulsification in the absence of a cargo (nucleic acids). The particle has a neutral charge at physiological pH and is stabilized by helper lipids and polyethyleneglycol (PEG)-conjugated lipids. The generalized polarization of 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan), which indicates the surface polarity caused by the invasion of water onto the surface, changes dynamically in response to pH and temperature, while the fluidity of the intra-particle compartment, as measured by the fluorescence anisotropy of 1,6-Diphenyl-1,3,5-hexatriene (DPH), is not affected. Even when the particle contains a high density of PEG on the surface, it shows a high fusogenecity to negatively charged liposomes in response to an acidic pH to a higher degree than a conventional cationic lipid. These characteristics suggest that the ssPalm particle possesses unique properties for delivering lipophilic drugs across the biomembrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. A nanoemulsion formulation of tamoxifen increases its efficacy in a breast cancer cell line.

    PubMed

    Tagne, Jean-Bosco; Kakumanu, Srikanth; Ortiz, Daniela; Shea, Thomas; Nicolosi, Robert J

    2008-01-01

    This paper reports on the preparation of a water-soluble nanoemulsion of the highly lipid-soluble drug tamoxifen (TAM). In addition, relative to a suspension of TAM, the nanoemulsion preparation demonstrated a greater zeta potential (increased negative charge) which has previously been associated with increasing drug/membrane permeability. This study also reports that relative to suspensions of TAM with particle sizes greater than 6000 nm, nanoemulsions of TAM, having mean particle sizes of 47 nm, inhibited cell proliferation 20-fold greater and increased cell apoptosis 4-fold greater in the HTB-20 breast cancer cell line. Thus, this work suggests that a nanoemulsion compared to a suspension preparation of TAM increases its anticancer properties relative to breast cancer.

  18. Comparative evaluation of propofol in nanoemulsion with solutol and soy lecithin for general anesthesia.

    PubMed

    Rittes, José Carlos; Cagno, Guilherme; Perez, Marcelo Vaz; Mathias, Ligia Andrade da Silva Telles

    2016-01-01

    The vehicle for propofol in 1 and 2% solutions is soybean oil emulsion 10%, which may cause pain on injection, instability of the solution and bacterial contamination. Formulations have been proposed aiming to change the vehicle and reduce these adverse reactions. To compare the incidence of pain caused by the injection of propofol, with a hypothesis of reduction associated with nanoemulsion and the occurrence of local and systemic adverse effects with both formulations. After approval by the CEP, patients undergoing gynecological procedures were included in this prospective study: control (n=25) and nanoemulsion (n=25) groups. Heart rate, noninvasive blood pressure and peripheral oxygen saturation were monitored. Demographics and physical condition were analyzed; surgical time and total volume used of propofol; local or systemic adverse effects; changes in variables monitored. A value of p<0.05 was considered significant. There was no difference between groups regarding demographic data, surgical times, total volume of propofol used, arm withdrawal, pain during injection and variables monitored. There was a statistically significant difference in pain intensity at the time of induction of anesthesia, with less pain intensity in the nanoemulsion group. Both lipid and nanoemulsion formulations of propofol elicited pain on intravenous injection; however, the nanoemulsion solution elicited a less intense pain. Lipid and nanoemulsion propofol formulations showed neither hemodynamic changes nor adverse effects of clinical relevance. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Reversible lipid accumulation and associated division arrest of Mycobacterium avium in lipoprotein-induced foamy macrophages may resemble key events during latency and reactivation of tuberculosis.

    PubMed

    Caire-Brändli, Irène; Papadopoulos, Alexia; Malaga, Wladimir; Marais, David; Canaan, Stéphane; Thilo, Lutz; de Chastellier, Chantal

    2014-02-01

    During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intracytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very-low-density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results. (i) Macrophages became foamy, and mycobacteria formed ILI, for which host triacylglycerides, rather than cholesterol, was essential. (ii) Lipid transfer occurred via mycobacterium-induced fusion between LB and phagosomes. (iii) Mycobacteria showed a thinned cell wall and became elongated but did not divide. (iv) Upon removal of VLDL, LB and ILI declined within hours, and simultaneous resumption of mycobacterial division restored the number of mycobacteria to the same level as that found in untreated control macrophages. This showed that the presence of ILI resulted in a reversible block of division without causing a change in the mycobacterial replication rate. Fluctuation between ILI either partially or fully extending throughout the mycobacterial cytoplasm was suggestive of bacterial cell cycle events. We propose that VLDL-driven FM constitute a well-defined cellular system in which to study changed metabolic states of intracellular mycobacteria that may relate to persistence and reactivation of tuberculosis.

  20. Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

    PubMed Central

    Caire-Brändli, Irène; Papadopoulos, Alexia; Malaga, Wladimir; Marais, David; Canaan, Stéphane; Thilo, Lutz

    2014-01-01

    During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intracytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very-low-density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results. (i) Macrophages became foamy, and mycobacteria formed ILI, for which host triacylglycerides, rather than cholesterol, was essential. (ii) Lipid transfer occurred via mycobacterium-induced fusion between LB and phagosomes. (iii) Mycobacteria showed a thinned cell wall and became elongated but did not divide. (iv) Upon removal of VLDL, LB and ILI declined within hours, and simultaneous resumption of mycobacterial division restored the number of mycobacteria to the same level as that found in untreated control macrophages. This showed that the presence of ILI resulted in a reversible block of division without causing a change in the mycobacterial replication rate. Fluctuation between ILI either partially or fully extending throughout the mycobacterial cytoplasm was suggestive of bacterial cell cycle events. We propose that VLDL-driven FM constitute a well-defined cellular system in which to study changed metabolic states of intracellular mycobacteria that may relate to persistence and reactivation of tuberculosis. PMID:24478064

  1. Study on antimicrobial potential of neem oil nanoemulsion against Pseudomonas aeruginosa infection in Labeo rohita.

    PubMed

    Mishra, Prabhakar; R S, Suresh Kumar; Jerobin, Jayakumar; Thomas, John; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-01-01

    Presence of several biochemical constituents in neem makes it an efficient antimicrobial agent for pathogenic diseases. The current investigation was aimed to assess the therapeutic potential of neem nanoemulsion as a control measure for Pseudomonas aeruginosa infection in freshwater fish Labeo rohita. The median lethal concentration (LC50) for the neem oil and neem nanoemulsion was 73.9 and 160.3 mg/L, respectively. The biomarker enzymes of treated fish tissues showed a significant difference in the level of glutathione reductase, catalase, and lipid peroxidation in neem oil-treated samples than in neem nanoemulsion-treated samples at P<0.05. The results were corroborative with histopathology and ultrastructural analysis. The bacterial infection of P. aeruginosa treated using neem nanoemulsion was more effective in both in vitro and in vivo methods. Present findings suggest that neem-based nanoemulsion has negligible toxicity to Rohu fishes. This makes neem-based nanoemulsion as an efficient therapeutic agent against P. aeruginosa infection, leading to its possible usage in the aquaculture industry.

  2. Nanoemulsion-Based Delivery Systems to Improve Functionality of Lipophilic Components

    PubMed Central

    Odriozola-Serrano, Isabel; Oms-Oliu, Gemma; Martín-Belloso, Olga

    2014-01-01

    The use of active lipophilic substances such as antimicrobials and health-related compounds in the food industry is still a challenge due to their poor water solubility and instability in food formulations. Nano-sized structures such as nanoemulsions of oil-in-water are regarded as useful tools with a great potential in the food sector to incorporate food ingredients. Reducing the size of the active compounds incorporated within a solution would increase the surface area per mass unit of nanoemulsions, thus enhancing solubility and stability in foods. In addition, the ability of the active lipids to penetrate across biological membranes is also enhanced, thus boosting their biological functionality. An overview of the most significant studies reporting data about the potential benefits of active lipid nanoemulsions over conventional emulsions is presented. PMID:25988126

  3. Tuneable stability of nanoemulsions fabricated using spontaneous emulsification by biopolymer electrostatic deposition.

    PubMed

    Saberi, Amir Hossein; Zeeb, Benjamin; Weiss, Jochen; McClements, David Julian

    2015-10-01

    Nanoemulsions can be formed spontaneously from surfactant-oil-water systems using low energy methods. In this work, we showed that the droplets in oil-in-water nanoemulsions fabricated by spontaneous emulsification could be coated with an anionic biopolymer (beet pectin) using electrostatic deposition. Nanoemulsions were formed by titrating oil (medium chain triglycerides) and surfactant (polyoxyethylene sorbitan monostearate+lauric arginate) mixtures into an aqueous solution (10 mM citrate buffer, pH 4). Lauric arginate was used to generate a positive charge on the droplet surfaces, thereby enabling subsequent electrostatic deposition of anionic pectin. Extensive droplet aggregation occurred when intermediate pectin concentrations were used due to bridging flocculation. However, stable anionic pectin-coated lipid droplets could be formed at high pectin concentrations. These results demonstrate the possibility of tailoring the functionality of lipid nanodroplets produced by spontaneous emulsification. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Facial resemblance enhances trust.

    PubMed

    DeBruine, Lisa M

    2002-07-07

    Organisms are expected to be sensitive to cues of genetic relatedness when making decisions about social behaviour. Relatedness can be assessed in several ways, one of which is phenotype matching: the assessment of similarity between others' traits and either one's own traits or those of known relatives. One candidate cue of relatedness in humans is facial resemblance. Here, I report the effects of an experimental manipulation of facial resemblance in a two-person sequential trust game. Subjects were shown faces of ostensible playing partners manipulated to resemble either themselves or an unknown person. Resemblance to the subject's own face raised the incidence of trusting a partner, but had no effect on the incidence of selfish betrayals of the partner's trust. Control subjects playing with identical pictures failed to show such an effect. In a second experiment, resemblance of the playing partner to a familiar (famous) person had no effect on either trusting or betrayals of trust.

  5. Preparation, characterization and in vivo evaluation of nanoemulsions for the controlled delivery of the antiobesity agent N-oleoylethanolamine.

    PubMed

    Wulff-Pérez, Miguel; Pavón, Francisco J; Martín-Rodríguez, Antonio; de Vicente, Juan; Alen, Francisco; de Fonseca, Fernando Rodríguez; Gálvez-Ruiz, María J; Serrano, Antonia

    2014-12-01

    > N-oleoylethanolamine (OEA) is a lipid mediator that acts as a satiety factor. The main limiting factor for its administration is its poor water solubility. We designed and characterized new nanoemulsions as delivery system for hydrophobic compounds such as OEA. The nanoemulsion components and preparation methods were selected in order to achieve the desired final properties. Then, we evaluated the in vivo properties of the nanoemulsions as drug-delivery systems testing the anorectic effects of OEA in rats after both intragastric and intraperitoneal administration. The in vivo toxicity of the nanoemulsions was evaluated after a 3-week treatment. Nanoemulsions proved to be stable, nontoxic and had no effect on feeding behavior when administered without OEA. The effects of OEA were observable after its oral and parenteral administration with the nanoemulsions to 24-h fasted rats, finding a better efficacy compared with a vehicle containing Tween(®) 20 (Sigma-Aldrich, MO, USA) after oral administration. These results support the efficacy of these nanoemulsions to deliver highly hydrophobic bioactive drugs.

  6. Physical Factors Affecting Plasmid DNA Compaction in Stearylamine-Containing Nanoemulsions Intended for Gene Delivery

    PubMed Central

    Silva, André Leandro; Júnior, Francisco Alexandrino; Verissimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Socrates Tabosa

    2012-01-01

    Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery. PMID:24281666

  7. Nanoemulsions prepared by a low-energy emulsification method applied to edible films

    USDA-ARS?s Scientific Manuscript database

    Catastrophic phase inversion (CPI) was used as a low-energy emulsification method to prepare oil-in-water (O/W) nanoemulsions in a lipid (Acetem)/water/nonionic surfactant (Tween 60) system. CPIs in which water-in-oil emulsions (W/O) are transformed into oil-in-water emulsions (O/W) were induced by ...

  8. Physical factors affecting plasmid DNA compaction in stearylamine-containing nanoemulsions intended for gene delivery.

    PubMed

    Silva, André Leandro; Alexandrino, Francisco; Verissimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Socrates Tabosa

    2012-06-18

    Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery.

  9. Fabrication, stability and efficacy of dual-component antimicrobial nanoemulsions: essential oil (thyme oil) and cationic surfactant (lauric arginate).

    PubMed

    Chang, Yuhua; McLandsborough, Lynne; McClements, David Julian

    2015-04-01

    The influence of a cationic surfactant (lauric arginate, LAE) on the physical properties and antimicrobial efficacy of thyme oil nanoemulsions was investigated. Nanoemulsions prepared from pure thyme oil were highly unstable due to Ostwald ripening, but they could be stabilized by adding a ripening inhibitor (corn oil) to the oil phase prior to homogenisation. The loading capacity and antimicrobial efficacy of thyme oil nanoemulsions were significantly increased by adding LAE. In the absence of LAE, at least 60 wt% corn oil had to be added to the lipid phase to inhibit Ostwald ripening; but in the presence of 0.1 wt% LAE, only 30 wt% corn oil was needed. LAE addition substantially increased the antimicrobial efficacy of the thyme oil nanoemulsions: 200 μg/ml thyme oil was needed to inhibit growth of a spoilage yeast (Zygosaccharomyces bailii) if LAE was added, whereas ⩾ 400 μg/ml was needed in the absence of LAE.

  10. Quantitative analysis of ligand effects on bioefficacy of nanoemulsion encapsulating depigmenting active.

    PubMed

    Atrux-Tallau, Nicolas; Lasselin, Juliette; Han, Sang-Hoon; Delmas, Thomas; Bibette, Jérôme

    2014-10-01

    Efficient skin delivery of active molecules is the main challenge to overcome in order to achieve significant therapeutic efficiency of cosmetics or dermo-pharmaceutical products. Nanocarriers such as nanoemulsions have been envisaged to overcome main challenges of active solubilization, protection and transport to their site of biological action. Nonetheless, their skin permeation is still limited and a new approach is required to significantly improve bioavailability. We here explored the possibility of increasing the whitening activity of a model active, licorice, by implementing a targeting approach of nanoemulsions to melanocyte cells. Targeting requires particle surface modification with specific molecules favoring nanoemulsion/cells contact through ligand-receptor interactions. The uniqueness of our strategy is that unlike classical covalent chemical grafting, we propose a self-assembled strategy based on a selection of amphiphilic ligands able to localize at nanoemulsion droplets interface. Four ligand candidates were thus assayed in terms of formulation and in vitro biological evaluation: a palmitoyl-peptide (palmitoyl-GQPR), a lipidized hyaluronic acid (caproyl-HA) and two amphiphilic actives (polydatin and isopilosine). A functional analysis based on a cellular assay of melanin inhibition was realized. The intrinsic properties of ligand candidates were first evaluated. Then, nanoemulsions encapsulating a drug model, licorice, and targeted with the different ligand candidates were assayed. The use of caproyl-HA significantly improved bioefficacy of the encapsulated licorice, suggesting a better interaction with the cells. The improved value observed was not attributed to a synergetic action as caproyl-HA did not evidence intrinsic melanogenesis modulation activity. In this study, we demonstrated the feasibility of targeting nanoemulsion droplets without chemical covalent modification of nanoemulsion droplets to increase bioefficacy of encapsulated drugs

  11. Investigation of the structural organization of cationic nanoemulsion/antisense oligonucleotide complexes.

    PubMed

    Bruxel, Fernanda; Vilela, José Mario Carneiro; Andrade, Margareth Spangler; Malachias, Ângelo; Perez, Carlos A; Magalhães-Paniago, Rogério; Oliveira, Mônica Cristina; Teixeira, Helder F

    2013-12-01

    Atomic force microscopy image analysis and energy dispersive X-ray diffraction experiments were used to investigate the structural organization of cationic nanoemulsion/oligonucleotide complexes. Oligonucleotides targeting topoisomerase II gene were adsorbed on cationic nanoemulsions obtained by means of spontaneous emulsification procedure. Topographical analysis by atomic force microscopy allowed the observation of the nanoemulsion/oligonucleotide complexes through three-dimensional high-resolution images. Flattening of the oil droplets was observed, which was reduced in the complexes obtained at high amount of adsorbed oligonucleotides. In such conditions, complexes exhibit droplet size in the 600nm range. The oligonucleotides molecules were detected on the surface of the droplets, preventing their fusion during aggregation. A lamellar structure organization was identified by energy dispersive X-ray diffraction experiments. The presence of the nucleic acid molecules led to a disorganization of the lipid arrangement and an expansion in the lattice spacing, which was proportional to the amount of oligonucleotides added.

  12. TOPICAL REVIEW: Nanoemulsions: formation, structure, and physical properties

    NASA Astrophysics Data System (ADS)

    Mason, T. G.; Wilking, J. N.; Meleson, K.; Chang, C. B.; Graves, S. M.

    2006-10-01

    We summarize procedures for producing 'nanoemulsions' comprised of nanoscale droplets, or 'nanoemulsions', methods for controlling the droplet size distribution and composition, and interesting physical properties of nanoemulsions. In contrast to more common microscale emulsions, nanoemulsions exhibit optical transparency at high droplet volume fractions, phi, surprisingly strong elasticity at low phi, and enhanced diffusive transport and shelf stability. For these reasons, nanoemulsions have great potential in a wide range of industries including pharmaceuticals, foods, and personal care products.

  13. Crystal structures and morphologies of fractionated milk fat in nanoemulsions.

    PubMed

    Truong, Tuyen; Morgan, Garry P; Bansal, Nidhi; Palmer, Martin; Bhandari, Bhesh

    2015-03-15

    The triacylglycerol (TAG) crystal structures and morphologies of fractionated milk lipids in nanoemulsions were investigated at 4°C. Droplet size (0.17 versus 1.20 μm), lipid composition (stearin versus olein) and cooling rate (1 versus 10°C min(-1)) had an influence on the structural properties. Five crystal polymorphs (α, β'1, β'2, β1, and β2) were formed with either triple and/or double chain length structures in the solid phases of the emulsified systems. X-ray scattering peak intensities were reduced with the nanoemulsion particles. The internal structure of TAG exhibited stacking of individual lamellar layers (3.8-4.2 nm). Various anisometric shapes of fat nanoparticles were formed due to a highly sharp curvature of the nano-size droplets. The shape of olein nanoparticles was more polyhedral compared to the stearin. TAG crystals arranged in a planar-layered organisation at the slower cooling rate. These differences imply that the nanometric confinement of oil droplets modifies the fat crystal habit.

  14. Understanding Nanoemulsion Formation and Developing a Procedure for Porous Material Growth using Assembled Nanoemulsions

    NASA Astrophysics Data System (ADS)

    Yeranossian, Vahagn Frounzig

    Nanoemulsions as an emerging technology have found many applications in consumer products, drug delivery, and even particle formation. However, knowledge gaps exist in how some of these emulsions are formed, specifically what pathways are traversed to reach the final state. Moreover, how these pathways affect the final properties of the nanoemulsions would affect the applications that these droplets possess. Some nanoemulsions possess unique properties, including the assembly of droplets. While the assembly of droplets is being studied in the Helgeson lab, work must be done to understand how the assembly itself could be used to control the growth of porous materials, such a hydrogels. Thus, this thesis aims to address two factors of nanoemulsions: the formation of water-in-oil nanoemulsions and the use of assemblying droplets in oil-in-water nanoemulsions to form macroporous hydrogels. To elucidate the formation mechanism of water-in-oil nanoemulsions, a combination of dynamic light scattering and small angle neutron scattering were used to study the intermediate and final states of the nanoemulsion during its formation. These nanoemulsions were prepared by slowly adding water to an oil and surfactant mixture and were diluted to effectively measure using scattering techniques without multiple scattering events. To develop a procedure to use assembled nanoemulsions for the growth of porous materials, a combination of optical microscopy and diffusional studies were employed. Optical microscopy images taken at various stages of the procedure help elucidate how the pore sizes of the final porous material is related to the droplet-rich domains of the assembled nanoemulsion. Meanwhile, diffusional measurements help confirm the size and interconnectedness of the macropores. From the work done in the completion of my thesis, the formation mechanism of the water-in-oil nanoemulsion studied has been elucidated. The neutron scattering measurements show that during the

  15. Recent Survey on Patents of Nanoemulsions.

    PubMed

    Patel, Rashmin B; Thakore, Shivam D; Patel, Mrunali R

    2016-01-01

    Colloidal systems are most prominent delivery systems mainly used as vehicles for the transportation, targeting the various types of biomolecules, proteins, peptides, synthetic medicinal agents. To provide concise information on patents that are directly or indirectly related to the nanoemulsions. The ample of research work going on with such system, in which small insoluble particle/droplets are dispersed within the immiscible secondary liquid referred to as continuous phase, is enormous. A highly praised colloidal system is nanoemulsion which possesses 'nano' sized droplets of one phase dispersed within second continuous phase. The characteristic features of nanoemulsion are their optical clarity, clear or bluish tint appearance and small globule size (20-200 nm) which makes them insensitive to gravitational instability, dilution and temperature. Above of all, achieving said properties using lower surfactant concentration and by supplying external energy differentiate them from microemulsion, which uses higher amount of surfactant thereby making them toxic for human body. Due to such variable advantages, researchers are engaged in going for the protecting their ideas in nanoemulsions by filling various patents. Patents in this review, covers various areas (types of drug delivery and applications) where nanoemulsion are used. Literature revealed that filing of patents on nanoemulsion increased tremendously during last 5 years and will increase in upcoming time as 21st century will be called as the century of nanomedicine.

  16. On the growth mechanisms of nanoemulsions.

    PubMed

    Nazarzadeh, Elijah; Anthonypillai, Tania; Sajjadi, Shahriar

    2013-05-01

    The shelf stability of nanoemulsions made by ultrasound, phase inversion composition, and the Ouzo effect was studied using a range of hydrocarbons, as the model oils, and surfactants. The cube of the average drop radius of the nanoemulsions displayed a linear increase with time. Both Ostwald ripening and coalescence can exhibit such behaviour. A new approach, based on the time evolution of drop size distribution, is proposed for unravelling the aging mechanism of nanoemulsions. Sequences of fall and rise in the average drop size of nanoemulsions were clearly observed. The decrease in the drop size could unambiguously be attributed to Ostwald ripening, but the increase could be due to either Ostwald ripening or coalescence/flocculation. Coalescence was identified as the dominant growth mechanism at low surfactant concentrations evidenced by drop size distribution broadening with time associated with the rise in the average drop size. Ostwald ripening was the dominant mechanism at higher surfactant concentrations where the drop size distributions broadened with time during the falls and narrowed with time during the rises of the average drop size. The nanoemulsions produced via the Ouzo process, displayed a coalescence-dependent transient stage and an Ostwald ripening dominated asymptotic regime in the absence of surfactant. The nanoemulsion produced via phase inversion was found to be the most stable one, however, still showed vulnerability to Ostwald ripening and flocculation in the long term.

  17. Food-grade nanoemulsions: formulation, fabrication, properties, performance, biological fate, and potential toxicity.

    PubMed

    McClements, David Julian; Rao, Jiajia

    2011-04-01

    Nanoemulsions fabricated from food-grade ingredients are being increasingly utilized in the food industry to encapsulate, protect, and deliver lipophilic functional components, such as biologically-active lipids (e.g., ω-3 fatty acids, conjugated linoleic acid) and oil-soluble flavors, vitamins, preservatives, and nutraceuticals. The small size of the particles in nanoemulsions (r<100 nm) means that they have a number of potential advantages over conventional emulsions-higher stability to droplet aggregation and gravitational separation, high optical clarity, ability to modulate product texture, and, increased bioavailability of lipophilic components. On the other hand, there may also be some risks associated with the oral ingestion of nanoemulsions, such as their ability to change the biological fate of bioactive components within the gastrointestinal tract and the potential toxicity of some of the components used in their fabrication. This review article provides an overview of the current status of nanoemulsion formulation, fabrication, properties, applications, biological fate, and potential toxicity with emphasis on systems suitable for utilization within the food and beverage industry. © Taylor and Francis Group, LLC

  18. Phytosterol structured algae oil nanoemulsions and powders: improving antioxidant and flavor properties.

    PubMed

    Chen, Xiao-Wei; Chen, Ya-Jun; Wang, Jin-Mei; Guo, Jian; Yin, Shou-Wei; Yang, Xiao-Quan

    2016-09-14

    Algae oil, enriched with omega-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFA), is known for its health benefits. However, protection against lipid oxidation as well as masking of unpleasant fishy malodors in algae oil enriched foods is a big challenge to achieve. In this study, we firstly achieved a one-pot ultrasound emulsification strategy (alternative heating-homogenization) to prepare phytosterol structured thermosensitive algae oil-in-water nanoemulsion stabilized by quillaja saponin. After spray drying, the resulting algae oil powders from the structured nanoemulsion templates exhibit an excellent reconstructed behavior, even after 30 d of storage. Furthermore, an enhanced oxidative stability was obtained by reducing both the primary and secondary oxidation products through formulation with β-sitosterol and γ-oryzanol, which are natural antioxidants. Following the results of headspace volatiles using dynamic headspace-gas chromatography-mass spectrometry (DHS-GC-MS), it was clear that the structured algae oil-loaded nanoemulsion and powder had lower levels of fishy off-flavour (e.g., (Z)-heptenal, decanal, ethanone, and hexadecenoic acid), whereas the control emulsion and oil powder without structure performed worse. This study demonstrated that the structure from phytosterols is an effective strategy to minimize the fishy off-flavour and maximize oxidative stability of both algae oil nanoemulsions and spray-dried powders, and opens up the possibility of formulation design in polyunsaturated oil encapsulates as novel delivery systems to apply in functional foods and beverages.

  19. Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage.

    PubMed

    Parveen, Rabea; Baboota, Sanjula; Ali, Javed; Ahuja, Alka; Vasudev, Suruchi S; Ahmad, Sayeed

    2011-05-01

    Silymarin is a complex mixture of four flavonolignan isomers (silybin, isosilybin, silydianin and silychristin) obtained from 'milk thistle' (Silybum marianum). This plant compound is used almost exclusively for hepatoprotection. Because of its low and poor oral bioavailability, silymarin was formulated as a nanoemulsion to increase its solubility (and so its oral bioavailability) as well as therapeutic activity. The present study assessed the hepatoprotective activity on Wistar rats by determining biochemical parameters and histopathological properties of the nanoemulsion formulation of silymarin against carbon tetrachloride (CCl(4))-induced hepatotoxicity. Hepatoprotective activity was evaluated by the activity of serum alkaline phosphatase, alanine transaminase and aspartate transaminase; antioxidative defence markers (concentration of reduced glutathione); oxidative stress parameter (thiobarbituric acid reactive substances) and liver histopathology. The nanoemulsion-treated group showed significant decreases in glutamate oxaloacetate transaminase, pyruvate transaminase, alkaline phosphotase, total bilirubin and tissue lipid peroxides and increased total protein, albumin, globulin and tissue glutathione as compared to toxicant. The results indicate an excellent potential of the nanoemulsion formulation for the reversal of CCl(4)-induced liver toxicity in rats as compared to standard silymarin.

  20. Development of β-Carotene-Loaded Organogel-Based Nanoemulsion with Improved In Vitro and In Vivo Bioaccessibility.

    PubMed

    Fan, Yuting; Gao, Luyu; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

    2017-08-02

    β-Carotene (BC), a naturally occurring lipophilic carotenoid, is beneficial for human health. However, its water solubility and bioavailability are low. In this study, organogel-based nanoemulsion was successfully prepared to improve the loading amount, solubility, and bioavailability of BC. Corn oil was selected as the oil phase for the organogel as a result of the greatest release amount of BC. Tween 20 was optimized as the emulsifier based on the highest extent of lipolysis and BC bioaccessibility. The nanoemulsion was a better alternative than the organogel according to both the extent of lipolysis and BC bioaccessibility. Cellular uptake of BC was significantly improved through organogel-based nanoemulsion compared to BC suspension. Caveolae-/lipid-raft-mediated route was the main endocytosis pathway. Pharmacokinetic results confirmed that the in vivo bioavailability of BC in nanoemulsion was 11.5-fold higher than that of BC oil. The information obtained suggested that organogel-based nanoemulsion may be an effective encapsulation system for delivery of insoluble and indigestible bioactive compounds.

  1. Does Facial Resemblance Enhance Cooperation?

    PubMed Central

    Giang, Trang; Bell, Raoul; Buchner, Axel

    2012-01-01

    Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces). A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system. PMID:23094095

  2. A review of multifunctional nanoemulsion systems to overcome oral and CNS drug delivery barriers.

    PubMed

    Ganta, Srinivas; Deshpande, Dipti; Korde, Anisha; Amiji, Mansoor

    2010-10-01

    The oral and central nervous systems (CNS) present a unique set of barriers to the delivery of important diagnostic and therapeutic agents. Extensive research over the past few years has enabled a better understanding of these physical and biological barriers based on tight cellular junctions and expression of active transporters and metabolizing enzymes at the luminal surfaces of the gastrointestinal (GI) tract and the blood-brain barrier (BBB). This review focuses on the recent understanding of transport across the GI tract and BBB and the development of nanotechnology-based delivery strategies that can enhance bioavailability of drugs. Multifunctional lipid nanosystems, such as oil-in-water nanoemulsions, that integrate enhancement in permeability, tissue and cell targeting, imaging, and therapeutic functions are especially promising. Based on strategic choice of edible oils, surfactants and additional surface modifiers, and different types of payloads, rationale design of multifunctional nanoemulsions can serve as a safe and effective delivery vehicle across oral and CNS barriers.

  3. Wound healing effects of nanoemulsion containing clove essential oil.

    PubMed

    Alam, Prawez; Ansari, Mohammad J; Anwer, Md Khalid; Raish, Mohammad; Kamal, Yoonus K T; Shakeel, Faiyaz

    2017-05-01

    The aim of this study was to investigate the wound healing effects of clove oil (CO) via its encapsulation into nanoemulsion. Optimized nanoemulsion (droplet size of 29.10 nm) was selected for wound healing investigation, collagen determination, and histopathological examination in rats. Optimized nanoemulsion presented significant would healing effects in rats as compared to pure CO. Nanoemulsion also presented significant enhancement in leucine content (0.61 mg/g) as compared to pure CO (0.50 mg/g) and negative control (0.31 mg/g). Histopathology of nanoemulsion treated rats showed no signs of inflammatory cells. These results suggested that nanoemulsion of CO was safe and nontoxic.

  4. Influence of emulsifier concentration on nanoemulsion gelation.

    PubMed

    Erramreddy, Vivek Vardhan; Ghosh, Supratim

    2014-09-23

    Nanoemulsion gels are a new class of soft materials that manifest stronger elasticity even at lower dispersed phase volume fraction. In this work, gelation in 40 wt % canola oil-in-water nanoemulsions was investigated as a function of emulsifier type (anionic sodium dodecyl sulfate (SDS) or nonionic Tween 20) and concentration. It was observed that the liquid nanoemulsions transformed into viscoelastic gels at a specific concentration range of SDS, whereas no gelation was observed for Tween 20. The apparent viscosity, yield stress, and storage modulus of the nanogels increased with SDS concentration until 15 times critical micelle concentration (CMC), thereafter decreased steadily as the gelation weakened beginning 20 CMC. Three regimes of colloidal interactions in the presence of emulsifier were proposed. (1) Repulsive gelation: at low SDS concentration (0.5-2 times CMC) the repulsive charge cloud around the nanodroplets acted as interfacial shell layer that significantly increased the effective volume fraction of the dispersed phase (ϕ(eff)). When ϕ(eff) became comparable to the volume fraction required for maximal random jamming, nanoemulsions formed elastic gels. (2) Attractive gelation: as the SDS concentration increased to 5-15 times CMC, ϕ(eff) dropped due to charge screening by more counterions from SDS, but depletion attractions generated by micelles in the continuous phase led to extensive droplet aggregation which immobilized the continuous phase leading to stronger gel formation. (3) Decline in gelation due to oscillatory structural forces (OSF): at very high SDS concentration (20-30 time CMC), structural forces were manifested due to the layered-structuring of excess micelles in the interdroplet regions resulting in loss of droplet aggregation. Tween 20 nanoemulsions, on the other hand, did not show repulsive gelation due to lack of charge cloud, while weak depletion attraction and early commencement of OSF regime leading to liquid-like behavior at

  5. Nanoemulsion: process selection and application in cosmetics--a review.

    PubMed

    Yukuyama, M N; Ghisleni, D D M; Pinto, T J A; Bou-Chacra, N A

    2016-02-01

    In recent decades, considerable and continuous growth in consumer demand in the cosmetics field has spurred the development of sophisticated formulations, aiming at high performance, attractive appearance, sensorial benefit and safety. Yet despite increasing demand from consumers, the formulator faces certain restrictions regarding the optimum equilibrium between the active compound concentration and the formulation base taking into account the nature of the skin structure, mainly concerning to the ideal penetration of the active compound, due to the natural skin barrier. Emulsion is a mixture of two immiscible phases, and the interest in nanoscale emulsion has been growing considerably in recent decades due to its specific attributes such as high stability, attractive appearance and drug delivery properties; therefore, performance is expected to improve using a lipid-based nanocarrier. Nanoemulsions are generated by different approaches: the so-called high-energy and low-energy methods. The global overview of these mechanisms and different alternatives for each method are presented in this paper, along with their benefits and drawbacks. As a cosmetics formulation is reflected in product delivery to consumers, nanoemulsion development with prospects for large-scale production is one of the key attributes in the method selection process. Thus, the aim of this review was to highlight the main high- and low-energy methods applicable in cosmetics and dermatological product development, their specificities, recent research on these methods in the cosmetics and consideration for the process selection optimization. The specific process with regard to inorganic nanoparticles, polymer nanoparticles and nanocapsule formulation is not considered in this paper. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  6. Nanoemulsion-based delivery systems for poorly water-soluble bioactive compounds: Influence of formulation parameters on Polymethoxyflavone crystallization.

    PubMed

    Li, Yan; Zheng, Jinkai; Xiao, Hang; McClements, David Julian

    2012-06-01

    Polymethoxyflavones (PMFs) extracted from citrus peel exhibit potent anti-cancer activity, but are highly hydrophobic molecules with poor solubility in both water and oil at ambient and body temperature, which limits their bioavailability. The possibility of encapsulating PMFs within nanoemulsion-based delivery systems to facilitate their application in nutraceutical and pharmaceutical products was investigated. The influence of oil type (corn oil, MCT, orange oil), emulsifier type (β-lactoglobulin, lyso-lecithin, Tween, and DTAB), and neutral cosolvents (glycerol and ethanol) on the formation and stability of PMF-loaded nanoemulsions was examined. Nanoemulsions (r < 100 nm) could be formed using high pressure homogenization for all emulsifier types, except DTAB. Lipid droplet charge could be altered from highly cationic (DTAB), to near neutral (Tween), to highly anionic (β-lactoglobulin, lyso-lecithin) by varying emulsifier type. PMF crystals formed in all nanoemulsions after preparation, which had a tendency to sediment during storage. The size, morphology, and aggregation of PMF crystals depended on preparation method, emulsifier type, oil type, and cosolvent addition. These results have important implications for the development of delivery systems for bioactive components that have poor oil and water solubility at application temperatures.

  7. Nanoemulsion-based delivery systems for poorly water-soluble bioactive compounds: Influence of formulation parameters on Polymethoxyflavone crystallization

    PubMed Central

    Li, Yan; Zheng, Jinkai; Xiao, Hang; McClements, David Julian

    2012-01-01

    Polymethoxyflavones (PMFs) extracted from citrus peel exhibit potent anti-cancer activity, but are highly hydrophobic molecules with poor solubility in both water and oil at ambient and body temperature, which limits their bioavailability. The possibility of encapsulating PMFs within nanoemulsion-based delivery systems to facilitate their application in nutraceutical and pharmaceutical products was investigated. The influence of oil type (corn oil, MCT, orange oil), emulsifier type (β-lactoglobulin, lyso-lecithin, Tween, and DTAB), and neutral cosolvents (glycerol and ethanol) on the formation and stability of PMF-loaded nanoemulsions was examined. Nanoemulsions (r < 100 nm) could be formed using high pressure homogenization for all emulsifier types, except DTAB. Lipid droplet charge could be altered from highly cationic (DTAB), to near neutral (Tween), to highly anionic (β-lactoglobulin, lyso-lecithin) by varying emulsifier type. PMF crystals formed in all nanoemulsions after preparation, which had a tendency to sediment during storage. The size, morphology, and aggregation of PMF crystals depended on preparation method, emulsifier type, oil type, and cosolvent addition. These results have important implications for the development of delivery systems for bioactive components that have poor oil and water solubility at application temperatures. PMID:22685367

  8. Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of curcumin for therapeutic intervention of sepsis.

    PubMed

    Shukla, Prashant; Dwivedi, Pankaj; Gupta, Pramod Kumar; Mishra, Prabhat Ranjan

    2014-11-01

    The objective of this study is to develop a nanostructured parenteral delivery system, laden with curcumin (CUR), for the therapeutic intervention of sepsis and associated pathologies. Nanoemulsions were fabricated using sonication and speed homogenization. Size and zeta potential were evaluated by dynamic light scattering and transmission electron microscopy analysis. Pharmacodynamic and pharmacokinetic studies were performed on a rat model of lipopolysaccharide (LPS)-induced sepsis. The drug content of optimized nanoemulsion (F5) formulation (particle size 246 ± 08 nm, polydispersity index (PDI) of 0.120, zeta potential of -41.1 ± 1.2 mV) was found to be 1.25 mg/ml. In vitro release studies demonstrated that F5 was able to sustain the release of CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its suitability for intravenous administration. Significant reduction of inflammatory mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma concentration (AUCF5/AUC CUR = 8.80) and tissue distribution of CUR in rats leading to a reduction in LPS-induced lung and liver injury due to less neutrophil migration, reduced TNF-α levels and oxidative stress (demonstrated by levels of lipid peroxides as well as carbonylated proteins) as confirmed by histopathological studies. The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.

  9. Exercise training accelerates the removal from plasma of LDL-like nanoemulsion in moderately hypercholesterolemic subjects.

    PubMed

    Ficker, Elisabeth S; Maranhão, Raul C; Chacra, Ana P M; Neves, Vanessa C; Negrão, Carlos E; Martins, Vanessa C N; Vinagre, Carmen G C de M

    2010-09-01

    Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events. Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with (14)C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24 h after injection to determine the fractional clearance rate (FCR, in h(-1)) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period. In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443+/-0.0126; 0.0602+/-0.0187, p=0.0187 and 0.0503+/-0.0203; 0.0686+/-0.0216, p=0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation. In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Children's Explanations of Family Resemblances.

    ERIC Educational Resources Information Center

    Horobin, Karen D.

    Four studies investigated children's explanations for family resemblance and species-typical characteristics, under different conditions of biological parentage and rearing environment. Participating were 226 children between 3 and 11 years. Children Children were presented with a number of different tasks, some involving people and some domestic…

  11. Vitamin E nanoemulsion activity on stored red blood cells.

    PubMed

    Silva, C A L; Azevedo Filho, C A; Pereira, G; Silva, D C N; Castro, M C A B; Almeida, A F; Lucena, S C A; Santos, B S; Barjas-Castro, M L; Fontes, A

    2017-06-01

    Stored red blood cells (RBCs) undergo numerous changes that have been termed RBC storage lesion, which can be related to oxidative damage. Vitamin E is an important antioxidant, acting on cell lipids. Thus, this study aimed to investigate vitamin E activity on stored RBCs. We prepared a vitamin E nanoemulsion that was added to RBC units and stored at 4 °C. Controls, without vitamin E, were kept under the same conditions. Reactive oxygen species (ROS) production was monitored for up to 35 days of storage. RBC elasticity was also evaluated using an optical tweezer system. Vitamin E-treated samples presented a significant decrease in ROS production. Additionally, the elastic constant for vitamin E-treated RBCs did not differ from the control. Vitamin E decreased the amount of ROS in stored RBCs. Because vitamin E acts on lipid oxidation, results suggest that protein oxidation should also be considered a key factor for erythrocyte elastic properties. Thus, further studies combining vitamin E with protein antioxidants deserve attention, aiming to better preserve overall stored RBC properties. © 2017 British Blood Transfusion Society.

  12. Mesoporous organohydrogels from thermogelling photocrosslinkable nanoemulsions

    NASA Astrophysics Data System (ADS)

    Helgeson, Matthew E.; Moran, Shannon E.; An, Harry Z.; Doyle, Patrick S.

    2012-04-01

    We report the formation of mesoporous organohydrogels from oil-in-water nanoemulsions containing an end-functionalized oligomeric gelator in the aqueous phase. The nanoemulsions exhibit an abrupt thermoreversible transition from a low-viscosity liquid to a fractal-like colloidal gel of droplets with mesoscale porosity and solid-like viscoelasticity with moduli approaching 100 kPa, possibly the highest reported for an emulsion-based system. We hypothesize that gelation is brought about by temperature-induced interdroplet bridging of the gelator, as shown by its dependence on the gelator chemistry. The use of photocrosslinkable gelators enables the freezing of the nanoemulsion’s microstructure into a soft hydrogel nanocomposite containing a large fraction of dispersed liquid hydrophobic compartments, and we show its use in the encapsulation and release of lipophilic biomolecules. The tunable structural, mechanical and optical properties of these organohydrogels make them a robust material platform suitable for a wide range of applications.

  13. Neem oil nanoemulsions: characterisation and antioxidant activity.

    PubMed

    Rinaldi, Federica; Hanieh, Patrizia Nadia; Longhi, Catia; Carradori, Simone; Secci, Daniela; Zengin, Gokhan; Ammendolia, Maria Grazia; Mattia, Elena; Del Favero, Elena; Marianecci, Carlotta; Carafa, Maria

    2017-12-01

    The aim of the present work is to develop nanoemulsions (NEs), nanosized emulsions, manufactured for improving the delivery of active pharmaceutical ingredients. In particular, nanoemulsions composed of Neem seed oil, contain rich bioactive components, and Tween 20 as nonionic surfactant were prepared. A mean droplet size ranging from 10 to 100 nm was obtained by modulating the oil/surfactant ratio. Physicochemical characterisation was carried out evaluating size, ζ-potential, microviscosity, polarity and turbidity of the external shell and morphology, along with stability in simulated cerebrospinal fluid (CSF), activity of Neem oil alone and in NEs, HEp-2 cell interaction and cytotoxicity studies. This study confirms the formation of NEs by Tween 20 and Neem oil at different weight ratios with small and homogenous dimensions. The antioxidant activity of Neem oil alone and in NEs was comparable, whereas its cytotoxicity was strongly reduced when loaded in NEs after interaction with HEp-2 cells.

  14. In vitro scleral lutein distribution by cyclodextrin containing nanoemulsions.

    PubMed

    Liu, Chi-Hsien; Lai, Kuan-Yu; Wu, Wei-Chi; Chen, Yu-Jui; Lee, Wei-Shiou; Hsu, Ching-Yun

    2015-01-01

    Lutein is a macular pigment that contributes to maintaining eye health. The development of lutein-laden nanocarriers for ocular delivery would have the advantages of user friendliness and cost-effectiveness. Nano-scaled vehicles such as cyclodextrin (CD) and nanoemulsion could overcome the barriers caused by the scleral structure. This study focused on the development of hybrid nanocarriers containing nanoemulsion and CD for scleral lutein accumulation. In the presence of the nanoemulsion, CD forms such as βCD and hydroxyethyl (HE) βCD increased the partition of lutein into the porcine sclera. A combination of nanoemulsion and 2% HEβCD enhanced lutein accumulation to 119±6 µg g(-1) h(-1), which was 9.2-fold higher than that with lutein suspension alone. We explored the dose effect of CD in nanoemulsion on scleral lutein and found that the scleral accumulation of lutein was enhanced by increasing the CD content. The novel nanoemulsion had 95% drug-loading efficiency and low cytotoxicity in retinal cells. The CD-modified nanoemulsion not only improved the stability and entrapment efficacy of lutein in the aqueous system but also enhanced scleral lutein accumulation. An increase in the partition coefficient of lutein in porcine sclera when using the CD-modified nanoemulsion was also confirmed.

  15. Curcumin nanoemulsion for transdermal application: formulation and evaluation.

    PubMed

    Rachmawati, Heni; Budiputra, Dewa Ken; Mauludin, Rachmat

    2015-04-01

    The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350 mg curcumin/10 g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0 ± 1.5 nm, 0.18 ± 0.0 and -5.9 ± 0.3 mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.

  16. Formulation and characterization of nanoemulsion of olanzapine for intranasal delivery.

    PubMed

    Kumar, Mukesh; Misra, Ambikanandan; Pathak, Kamla

    2009-01-01

    The objective was to formulate an olanzapine nanoemulsion that could potentially deliver the drug directly to the brain following intranasal administration. The nanoemulsions were prepared using the water titration method. The mucoadhesive character was imparted by the addition of 0.5%w/w chitosan and 0.5%w/w polycarbophil and was characterized for drug content, pH, percentage transmittance, globule size, zeta potential, and PDI. The composition (%w/w) of the optimized olanzapine nanoemulsion was capmul MCM, tween 80, and a mixture of 1:1 ratio of polyethylene glycol 400 and ethanol, and aqueous phase in a ratio of 15:35:17.5:32.5. The optimized olanzapine nanoemulsion exhibited a high diffusion coefficient and no nasal cilio-toxicity. The drug release followed the Higuchi model. The optimized nanoemulsions were found to be stable for 3 months.

  17. Challenges associated in stability of food grade nanoemulsions.

    PubMed

    Karthik, P; Ezhilarasi, P N; Anandharamakrishnan, C

    2017-05-03

    Food grade nanoemulsions are being increasingly used in the food sector for their physico-chemical properties towards efficient encapsulation, entrapment of bioactive compounds, solubilization, targeted delivery, and bioavailability. Nanoemulsions are considered as one of the important vehicles for the sustained release of food bioactive compounds due to their smaller size (nm), increased surface area, and unique morphological characteristics. Nanoemulsification is an ideal technique for fabricating the bioactive compounds in a nano form. Formation and stabilization of nanoemulsion depends on the physi-cochemical characteristics of its constituents including oil phase, aqueous phase, and emulsifiers. This review is mainly focused on the instability mechanisms of nanoemulsion such as flocculation, Ostwald ripening, creaming, phase separation, coalescence, and sedimentation. Further, the major factors associated with these instability mechanisms like ionic strength, temperature, solubilization, particle size distribution, particle charge, pH strength, acid stability, and heat treatment are also discussed. Finally, safety issues of food grade nanoemulsions are highlighted.

  18. Nanoemulsion: an advanced mode of drug delivery system.

    PubMed

    Jaiswal, Manjit; Dudhe, Rupesh; Sharma, P K

    2015-04-01

    An advanced mode of drug delivery system has been developed to overcome the major drawbacks associated with conventional drug delivery systems. This review gives a detailed idea about a nanoemulsion system. Nanoemulsions are nano-sized emulsions, which are manufactured for improving the delivery of active pharmaceutical ingredients. These are the thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent, i.e., surfactant and co-surfactant. The droplet size of nanoemulsion falls typically in the range 20-200 nm. The main difference between emulsion and nanoemulsion lies in the size and shape of particles dispersed in the continuous phase. In this review, the attention is focused to give a basic idea about its formulation, method of preparation, characterization techniques, evaluation parameters, and various applications of nanoemulsion.

  19. Development of a nanoemulsion of Phyllanthus emblica L. branch extract.

    PubMed

    Chaiittianan, Rungsiri; Sripanidkulchai, Bungorn

    2014-12-01

    For potential topical administration, we formulated a nanoemulsion containing phenolic constituents of Phyllanthus emblica branch extract. The nanoemulsion has high entrapment efficiency, small particle size, is stable, and can release its main chemical components. Branches of P. emblica were extracted with 50% ethanol (EPE) with 5.4% yield. HPLC analysis indicated several phenolic compounds, including gallic acid, vanillic acid, epigallocatechin (EGC), epigallocatechin gallate (EGCG) and ellagic acid. These were selected as chemical markers of EPE in the nanoemulsion development. The nanoemulsion was prepared by microemulsion techniques with hot high pressure homogenization. A ternary phase diagram was constructed to obtain the optimized nanoemulsion. The obtained transparent EPE nanoemulsion is composed of isopropyl myristate (0.6% w/w), Brij® 78 (0.35% w/w), and 0.15% (w/w) EPE. The optimized EPE nanoemulsion had a median particle size of 191.63 ± 4.07 nm with a narrow particle size distribution, a zeta potential of -10.19 ± 0.54 mV, high entrapment efficiency at 67.99 ± 0.87% and good stability at 4 °C after 90 d of storage. The release of active ingredients from the EPE nanoemulsion was slower than that of the EPE aqueous formulation. The loading ratios of the five phenolic compounds were high, with relative order of EGC > EGCG > vanillic acid > gallic acid > ellagic acid, resulting in slow release profiles of EGC and EGCG in the EPE nanoemulsion. In conclusion, the obtained EPE nanoemulsion has good characteristics for future clinical trials.

  20. Perfluorocarbon nanoemulsions with fluorescent, colloidal and magnetic properties

    PubMed Central

    Janjic, Jelena M.; Shao, Pin; Zhang, Shaojuan; Yang, Xun; Patel, Sravan K.; Bai, Mingfeng

    2014-01-01

    Bimodal imaging agents that combine magnetic resonance imaging (MRI) and nearinfrared (NIR) imaging formulated as nanoemulsions became increasingly popular for imaging inflammation in vivo. Quality of in vivo imaging using nanoemulsions is directly dependent on their integrity and stability. Here we report the design of nanoemulsions for bimodal imaging, where both photostability and colloidal stability are equally addressed. A highly chemically and photo stable quaterrylenediimide dye was introduced into perfluoro-15-crown-5 ether (PCE) nanoemulsions. The nanoemulsions were prepared with PCE and Miglyol 812N mixed at 1:1 v/v ratio as internal phase stabilized by non-ionic surfactants. Data shows exceptional colloidal stability demonstrated as unchanged droplet size (~130 nm) and polydispersity (<0.15) after 182 days follow up at both 4 and 25 °C. Nanoemulsions also sustained the exposure to mechanical and temperature stress, and prolonged exposure to light without changes in droplet size, 19F signal or fluorescence signal. No toxicity was observed in vitro in model inflammatory cells upon 24 h exposure while confocal microscopy showed that nanoemulsions droplets accumulated in the cytoplasm. Overall, our data demonstrates that design of bimodal imaging agents requires consideration of stability of each imaging component and that of the nanosystem as a whole to achieve excellent imaging performance. PMID:24674463

  1. Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination.

    PubMed

    Sharma, Navneet; Ojha, Himanshu; Pathak, Dharam Pal; Goel, Rajeev; Sharma, Rakesh Kumar

    2017-01-01

    p-tertbutylcalix[4]arene loaded nanoemulsion has been designed, characterized and evaluated for skin decontamination of radionuclides of interest in nuclear and radiological emergencies. Further, nanoemulsion was evaluated for Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity. Ex-vivo skin complexation studies were conducted using High-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). Skin studies at dermal and cyto-dermal level have been carried out using techniques such as florescence microscopy, Differential scanning calorimetry (DSC), Flow cytometry, Confocal microscopy, Prestoblue and Comet assay. HR-SF-ICPMS study confirmed >95% complexation of surrogate nuclides of thallium and Iodine applied on excised rat skin mounted over Franz diffusion cell. Temporal analysis of aliquots obtained from Franz diffusion cell using UV-Vis absorption spectroscopy indicated that only 3.37% of formulation permeates through the skin. Skin penetration study of rhodamine 123 nanoemulsion carried out using florescence microscopy confirmed that formulation remains localised in epidermis of rat skin. DSC data confirmed skin compatibility of nanoemulsion, as no lipid extraction was observed from skin. In-vitro cell viability and cellular uptake assays performed on human skin fibroblasts prove no cellular uptake and cytotoxic effects. Comet assay, cell cycle arrest, and apoptosis-inducing mechanistic studies prove that prepared nanoemulsion is safe at cellular level. Taken together, data indicate that p-tertbutylcalix[4]arene nanoemulsion is both effective and safe formulation to use on skin for radio-decontamination. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of PEG surface conformation on anticancer activity and blood circulation of nanoemulsions loaded with tocotrienol-rich fraction of palm oil.

    PubMed

    Alayoubi, Alaadin; Alqahtani, Saeed; Kaddoumi, Amal; Nazzal, Sami

    2013-10-01

    Tocotrienol-rich fraction of palm oil, which contains the isomers of vitamin E, was shown to possess potent anticancer activity against mammary adenocarcinoma cell lines. Its clinical use, however, is limited by poor oral bioavailability and short half-life. Previously, we developed tocotrienol-rich lipid nanoemulsions for intravenous administration. The objective of this study was to investigate the effect of surface grafted polyethylene glycol (PEG) on the properties of the nanoemulsions. PEGylation was achieved by the addition of equimolar PEG groups using poloxamer or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)2000] (PEG2000-DSPE). The effect of PEG surface topography on the antiproliferative activity of nanoemulsions against mammary adenocarcinoma cells, their susceptibility to protein adsorption, and its effect on blood hemolysis and circulation time was investigated. Nanoemulsions PEGylated with poloxamer or PEG2000-DSPE were stable under physical stress. Poloxamer nanoemulsion, however, displayed higher uptake and potency against MCF-7 tumor cells in 2D and 3D culture and increased hemolytic effect and susceptibility to IgG adsorption, which was reflected in its rapid clearance and short circulation half-life (1.7 h). Conversely, PEGylation with PEG2000-DSPE led to a 7-fold increase in mean residence time (12.3 h) after IV injection in rats. Reduced activity in vitro and improved circulation time suggested strong shielding of plasma proteins from the droplets. Differences between the nanoemulsions were attributed to polymer imbibitions and the differences in PEG conformation and density on the surface of the droplets.

  3. Archaic artifacts resembling celestial spheres

    NASA Astrophysics Data System (ADS)

    Dimitrakoudis, S.; Papaspyrou, P.; Petoussis, V.; Moussas, X.

    We present several bronze artifacts from the Archaic Age in Greece (750-480 BC) that resemble celestial spheres or forms of other astronomical significance. They are studied in the context of the Dark Age transition from Mycenaean Age astronomical themes to the philosophical and practical revival of astronomy in the Classical Age with its plethora of astronomical devices. These artifacts, mostly votive in nature are spherical in shape and appear in a variety of forms their most striking characteristic being the depiction of meridians and/or an equator. Most of those artifacts come from Thessaly, and more specifically from the temple of Itonia Athena at Philia, a religious center of pan-Hellenic significance. Celestial spheres, similar in form to the small artifacts presented in this study, could be used to measure latitudes, or estimate the time at a known place, and were thus very useful in navigation.

  4. [Preparation of Kushen-Dilong nanoemulsion gel and transdermal characterization in vitro].

    PubMed

    He, Kui-Bang; Wang, Ying-Zi; Feng, Ai-Ling; Duan, Fei-Peng; Li, Cai-Xia; Sun, Xiu-Yu

    2013-08-01

    To prepare Kushen-Dilong nanoemulsion and nanoemuls-ion gel, and investigate its content, physical and chemical properties. Their transdermal properties in vitro were studied as well. IPM acted as oil phase, EL35 as surfactant, EtOH as cosurfactant, Pheretima aqueous solution was added dropwise to the oil phase to prepare Kushen-Dilong nanoemulsion at room temperature using magnetic stirring. HPLC was used to determine the content of matrine and oxymatrine in the nanoemulsion. Transmission electron microscopy and laser particle size analyzer was used to determine the shape and size of the nanoemulsion. NP700 was used as substrate to prepare Kushen-Dilong nanoemulsion gel. Franz diffusion cell was used for the nanoemulsion and gel transdermal characteristics in vitro. The Kushen-Dilong nanoemulsion was O/W nanoemulsion, its uniform particle size was 20.6 nm with roundness appearance and stable content. The steady-state permeation rate of Kushen-Dilong nanoemulsion, nanoemulsion gel, saturated aqueous solution, hydro gel were 0.1484, 0.1183, 0.0306, 0.0321 mg x cm(-2) x h(-1), respectively. The 24 h cumulative infiltration and infiltration rate of Kushen-Dilong nanoemulsion and nanoemulsion gel were better than the saturated aqueous solution and hydro gel, which could provide a new dosage form for Kushen-Dilong transdermal drug delivery.

  5. Droplet microfluidics with a nanoemulsion continuous phase.

    PubMed

    Gu, Tonghan; Yeap, Eunice W Q; Somasundar, Ambika; Chen, Ran; Hatton, T Alan; Khan, Saif A

    2016-07-05

    We present the first study of a novel, generalizable method that uses a water-in-oil nanoemulsion as the continuous phase to generate uniform aqueous micro-droplets in a capillary-based microfluidic system. We first study the droplet generation mechanism in this system and compare it to the more conventional case where a simple oil/solvent (with surfactant) is used as the continuous phase. Next, we present two versatile methods - adding demulsifying chemicals and heat treatment - to allow active online chemical interaction between the continuous and dispersed phases. These methods allow each generated micro-droplet to act as a well-mixed micro-reactor with walls that are 'permeable' to the nanoemulsion droplets and their contents. Finally, we demonstrate an application of this system in the fabrication of uniform hydrogel (alginate) micro-beads with control over particle properties such as size and swelling. Our work expands the toolbox of droplet-based microfluidics, enabling new opportunities and applications involving active colloidal continuous phases carrying chemical payloads, both in advanced materials synthesis and droplet-based screening and diagnostic methods.

  6. Nanoemulsions: the properties, methods of preparation and promising applications

    NASA Astrophysics Data System (ADS)

    Koroleva, M. Yu; Yurtov, Evgenii V.

    2012-01-01

    The properties of nanoemulsions and various methods for their preparation including the high-energy and low-energy emulsification methods and the combined methods are reviewed. Among the high-energy methods, the emphasis is placed on high-energy stirring, ultrasonic emulsification, high-pressure homogenization including microfluidics and membrane emulsification. Among the low-energy emulsification methods, the attention is focused on the phase inversion temperature method, the emulsion inversion point method and the spontaneous emulsification. Using a combined method, which includes the high-energy and low-energy emulsification, it is possible to prepare reverse nanoemulsions in highly viscous systems. Main advantages and limitations of different methods of nanoemulsion preparation are discussed and the potential fields of nanoemulsion applications are considered. The bibliography includes 255 references.

  7. Cationic nanoemulsions as potential carriers for intracellular delivery

    PubMed Central

    Khachane, P.V.; Jain, A.S.; Dhawan, V.V.; Joshi, G.V.; Date, A.A.; Mulherkar, R.; Nagarsenker, M.S.

    2014-01-01

    Successful cytosolic delivery enables opportunities for improved treatment of various genetic disorders, infectious diseases and cancer. Cationic nanoemulsions were designed using alternative excipients and evaluated for particle size, charge, effect of sterilization on its stability, DNA condensation potential and cellular uptake efficiency. Various concentrations of non-ionic and ionic stabilizers were evaluated to design formula for colloidally stable cationic nanoemulsion. The nanoemulsion comprised of 5% Capmul MCM, 0.5% didodecyldimethylammonium bromide (DDAB), 1% phospholipid, 1% Poloxamer 188 and 2.25% glycerol and possessed particle size of 81.6 ± 3.56 nm and 137.1 ± 1.57 nm before and after steam sterilization, respectively. DNA condensation studies were carried out at various nanoemulsion: DNA ratios ranging from 1:1 to 10:1. Cell uptake studies were conducted on human embryonic kidney (HEK) cell lines which are widely reported for transfection studies. The nanoemulsions showed excellent cellular uptake as evaluated by fluorescence microscopy and flow cytometry. Overall, a colloidally stable cationic nanoemulsion with good DNA condensation ability was successfully fabricated for efficient cytosolic delivery and potential for in vivo effectiveness. PMID:25972740

  8. Pentyl Gallate Nanoemulsions as Potential Topical Treatment of Herpes Labialis.

    PubMed

    Kelmann, Regina G; Colombo, Mariana; De Araújo Lopes, Sávia Caldeira; Nunes, Ricardo J; Pistore, Morgana; Dall Agnol, Daniele; Rigotto, Caroline; Silva, Izabella Thais; Roman, Silvane S; Teixeira, Helder F; Oliveira Simões, Cláudia M; Koester, Letícia S

    2016-07-01

    Previous studies have demonstrated the antiherpes activity of pentyl gallate (PG), suggesting that it could be a promising candidate for the topical treatment of human herpes labialis. PG low aqueous solubility represents a major drawback to its incorporation in topical dosage forms. Hence, the feasibility of incorporating PG into nanoemulsions, the ability to penetrate the skin, to inhibit herpes simplex virus (HSV)-1 replication, and to cause dermal sensitization or toxicity were evaluated. Oil/water nanoemulsions containing 0.5% PG were prepared by spontaneous emulsification. The in vitro PG distribution into porcine ear skin after topical application of nanoemulsions was assessed, and the in vitro antiviral activity against HSV-1 replication was evaluated. Acute dermal toxicity and risk of dermal sensitization were evaluated in rat model. Nanoemulsions presented nanometric particle size (from 124.8 to 143.7 nm), high zeta potential (from -50.1 to -66.1 mV), loading efficiency above 99%, and adequate stability during 12 months. All formulations presented anti-HSV-1 activity. PG was able to reach deeper into the dermis more efficiently from the nanoemulsion F4. This formulation as well as PG were considered safe for topical use. Nanoemulsions seem to be a safe and effective approach for topically delivering PG in the treatment of human herpes labialis infection.

  9. Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

    PubMed

    Thakkar, Hetal P; Khunt, Amit; Dhande, Rahul D; Patel, Arpita A

    2015-08-04

    Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

  10. Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

    PubMed

    Thakkar, Hetal P; Khunt, Amit; Dhande, Rahul D; Patel, Arpita A

    2015-01-01

    Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

  11. Lecithin based nanoemulsions: A comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation.

    PubMed

    Hoeller, Sonja; Sperger, Andrea; Valenta, Claudia

    2009-03-31

    Charged drug delivery systems are interesting candidates for the delivery of drugs through skin. In the present study, it was possible to create negatively and positively charged oil/water nanoemulsions by using sucrose laureate and polysorbate 80 as non-ionic surfactants. The positively charged nanoemulsions were generated by adding cationic phytosphingosine (PS). The relationship between the physicochemical properties of the nanoemulsions was shown by particle size and zeta potential measurements. These properties were dependent on the type of non-ionic surfactant and the concentration of PS. Furthermore the cationic PS had a positive impact on the skin permeation rates (flux) of the incorporated model drugs fludrocortisone acetate and flumethasone pivalate. An enhancement factor between 1.1 and 1.5 was obtained in relation to the control. The interaction of pre-impregnated porcine skin with positively and negatively charged nanoemulsions was confirmed by DSC analysis. The generated DSC-curves showed a slight difference in the phase transition temperature assigned to the characteristic lipid transition. However, it was not possible to assign the effect to one of the ingredients in the multicomponent system.

  12. Prediction of Permeation and Cellular Transport of Silybum marianum Extract Formulated in a Nanoemulsion by Using PAMPA and Caco-2 Cell Models.

    PubMed

    Piazzini, Vieri; Rosseti, Chiara; Bigagli, Elisabetta; Luceri, Cristina; Bilia, Anna Rita; Bergonzi, Maria Camilla

    2017-05-04

    The present study explores the potential of nanoemulsion, a lipid drug delivery system, to improve solubility and oral absorption of Silybum marianum extract. The optimized formulation contained 40 mg/mL of commercial extract (4 % w/w) and it was composed of 2.5 g labrasol (20 %) as the oil phase, 1.5 g cremophor EL as the surfactant, and 1 g labrafil as the cosurfactant (mixture surfactant/cosurfactant, 20 %).The system was characterized by dynamic light scattering, transmission electron microscopy, and HPLC-DAD analyses in order to evaluate size, homogeneity, morphology, and encapsulation efficiency. Physical and chemical stabilities were assessed during 40 days at 4 °C and 3 months at 25 °C. Stability in simulated gastric fluid followed by simulated intestinal conditions was also considered. In vitro permeation studies were performed to determine the suitability of the prepared nanoemulsion for oral delivery. Different models such as the parallel artificial membrane permeability assay and Caco-2 cell lines were applied.The nanoemulsion showed a good solubilizing effect of the extract, with a pronounced action also on its permeability, in respect to a saturated aqueous solution. The Caco-2 test confirmed the parallel artificial membrane permeability assay results and they revealed the suitability of the prepared nanoemulsion for oral delivery. Georg Thieme Verlag KG Stuttgart · New York.

  13. Thyme oil nanoemulsions coemulsified by sodium caseinate and lecithin.

    PubMed

    Xue, Jia; Zhong, Qixin

    2014-10-08

    Many nanoemulsions are currently formulated with synthetic surfactants. The objective of the present work was to study the possibility of blending sodium caseinate (NaCas) and lecithin to prepare transparent thyme oil nanoemulsions. Thyme oil was emulsified using NaCas and soy lecithin individually or in combination at neutral pH by shear homogenization. The surfactant combination improved the oil content in transparent/translucent nanoemulsions, from 1.0% to 2.5% w/v for 5% NaCas with and without 1% lecithin, respectively. Nanoemulsions prepared with the NaCas-lecithin blend had hydrodynamic diameters smaller than 100 nm and had significantly smaller and more narrowly distributed droplets than those prepared with NaCas or lecithin alone. Particle dimension and protein surface load data suggested the coadsorption of both surfactants on oil droplets. These characteristics of nanoemulsions minimized destabilization mechanisms of creaming, coalescence, and Ostwald ripening, as evidenced by no significant changes in appearance and particle dimension after 120-day storage at 21 °C.

  14. Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.

    PubMed

    Ahmad, Usama; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees; Siddiqui, Sahabjada

    2017-05-14

    Nanoemulsion of silymarin was developed and optimized. Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8% v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were used as oil phase, surfactant and co-surfactant while distilled water (65.22% v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of particle size, viscosity, electrical conductivity and refractive index. Further, in vitro release, in vivo pharmacokinetic study, stability study and cancer cell line studies were also performed. The optimized formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also showed higher AUC (p < .01) and Cmax (p < .01) and shorter Tmax (p < .05) compared with conventional and standard suspensions of silymarin. The stability study also showed considerably stable formulations at refrigerator temperature as compared with room temperature (p > .05). The cancer cell line studies also confirmed that silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation (p < .05). Our results concluded that nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.

  15. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy.

    PubMed

    Jores, Katja; Mehnert, Wolfgang; Drechsler, Markus; Bunjes, Heike; Johann, Christoph; Mäder, Karsten

    2004-03-05

    Recently, colloidal dispersions made from mixtures of solid and liquid lipids were described to combine controlled release characteristics with higher drug loading capacities than solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets which solubilize the drug and which are embedded in a solid lipid matrix. The structures of SLN and NLC based on glyceryl behenate and medium chain triglycerides were characterized by photon correlation spectroscopy (PCS) and laser diffraction (LD), field-flow fractionation (FFF) with multi-angle light scattering detection (MALS), and cryo transmission electron microscopy (cryo TEM). PCS indicates that SLN and NLC differ from a nanoemulsion with respect to Brownian motion due to asymmetric particle shapes. Non-spherical particles, in case of SLN and NLC, lead to higher polydispersity indices compared to the nanoemulsion. In FFF, the nanodroplets elute much earlier than SLN- and NLC-platelets although their PCS and LD data show similar particle sizes. In TEM platelet (for SLN), oil loaded platelet ("nanospoons"; for NLC) and droplet (for nanoemulsion) structures were observed. In contrast to literature reports, the investigated SLN appear as thin platelets. NLC are found to be lipid platelets with oil spots sticking on the surface. Very short diffusion pathways in platelets, increased water-lipid interfaces and low drug incorporation in crystalline lipids are the drawback of SLN and NLC compared to conventional nanoemulsions.

  16. Mathematical Modeling and Experimental Validation of Nanoemulsion-Based Drug Transport across Cellular Barriers.

    PubMed

    Kadakia, Ekta; Shah, Lipa; Amiji, Mansoor M

    2017-07-01

    Nanoemulsions have shown potential in delivering drug across epithelial and endothelial cell barriers, which express efflux transporters. However, their transport mechanisms are not entirely understood. Our goal was to investigate the cellular permeability of nanoemulsion-encapsulated drugs and apply mathematical modeling to elucidate transport mechanisms and sensitive nanoemulsion attributes. Transport studies were performed in Caco-2 cells, using fish oil nanoemulsions and a model substrate, rhodamine-123. Permeability data was modeled using a semi-mechanistic approach, capturing the following cellular processes: endocytotic uptake of the nanoemulsion, release of rhodamine-123 from the nanoemulsion, efflux and passive permeability of rhodamine-123 in aqueous solution. Nanoemulsions not only improved the permeability of rhodamine-123, but were also less sensitive to efflux transporters. The model captured bidirectional permeability results and identified sensitive processes, such as the release of the nanoemulsion-encapsulated drug and cellular uptake of the nanoemulsion. Mathematical description of cellular processes, improved our understanding of transport mechanisms, such as nanoemulsions don't inhibit efflux to improve drug permeability. Instead, their endocytotic uptake, results in higher intracellular drug concentrations, thereby increasing the concentration gradient and transcellular permeability across biological barriers. Modeling results indicated optimizing nanoemulsion attributes like the droplet size and intracellular drug release rate, may further improve drug permeability.

  17. Stability studies of silymarin nanoemulsion containing Tween 80 as a surfactant.

    PubMed

    Parveen, Rabea; Baboota, Sanjula; Ali, Javed; Ahuja, Alka; Ahmad, Sayeed

    2015-01-01

    Silymarin, a flavonolignan from "milk thistle" (Silybum marianum) plant is used almost exclusively for hepatoprotection. Because of its low bioavailability, it was incorporated into a nanoemulsion formulation. The aim of the present study was to check the stability of silymarin nanoemulsion at different temperatures for 3 months. The oil-in-water based nanoemulsion formulation was prepared by titration method. Silymarin nanoemulsion was characterized by droplet size, viscosity, and refractive index. Droplet size, viscosity, and refractive index were determined every month. The shelf-life of silymarin nanoemulsion was determined by accelerated stability testing. It was found that there was no significant change in the droplet size, viscosity, and refractive index at refrigerator and room temperature during the period of 3 months. The half-life of the optimized nanoemulsion formulation was found to be 4.74 years at room temperature. These results indicated that stability of silymarin can be enhanced in nanoemulsion formulation using Tween 80 as a surfactant.

  18. Investigation of Factors Affecting Aerodynamic Performance of Nebulized Nanoemulsion

    PubMed Central

    Kamali, Hosein; Abbasi, Shayan; Amini, Mohammad Ali; Amani, Amir

    2016-01-01

    This work aimed to prepare a nanoemulsion preparation containing budesonide and assess its aerodynamic behavior in comparison with suspension of budesonide. In-vitro aerodynamic performance of the corresponding micellar solution (ie. nanoemulsion preparation without oil) was investigated too. Nanoemulsions of almond oil containing budesonide, as a hydrophobic model drug molecule, were prepared and optimized. Then, the effect of variation of surfactant/co-surfactant concentration on the aerodynamic properties of the nebulized aerosol was studied. The results indicated that the most physically stable formulation makes the smallest aerodynamic size. The concentration of co-surfactant was also shown to be critical in determination of aerodynamic size. Furthermore, the optimized sample, with 3% w/w almond oil, 20% w/w Tween 80+Span 80 and 2% w/w ethanol showed a smaller MMAD in comparison with the commercially available suspension and the micellar solution. PMID:28243265

  19. Development of topical hydrogels containing genistein-loaded nanoemulsions.

    PubMed

    de Vargas, Bethânia Andrade; Bidone, Juliana; Oliveira, Laura Karsburg; Koester, Leticia Scherer; Bassani, Valquiria Linck; Teixeira, Helder Ferreira

    2012-04-01

    This article describes the development of topical hydrogels containing genistein-loaded nanoemulsions, obtained by means of spontaneous emulsification. This procedure yielded monodisperse nanoemulsions in a sub 250 nm range exhibiting negative zeta-potential and low viscosity. The formulations were incorporated into acrylic-acid hydrogels in order to have their viscosity adjusted for topical application. The semisolid formulations exhibit non-Newtonian pseudoplastic behavior. The skin permeation/retention of genistein from formulations was carried out using porcine ear skin mounted in Franz diffusion cells under sink conditions. The results showed a slow flow of genistein through the skin. Higher amount of genistein was detected into the skin from the formulation composed by medium chain triglycerides as oily core when compared to the octyldodecanol one. The overall results show that hydrogels containing genistein-loaded nanoemulsions could be considered as a promising formulation to delivery isoflavones into the skin.

  20. The impact of vaporized nanoemulsions on ultrasound-mediated ablation

    PubMed Central

    2013-01-01

    Background The clinical feasibility of using high-intensity focused ultrasound (HIFU) for ablation of solid tumors is limited by the high acoustic pressures and long treatment times required. The presence of microbubbles during sonication can increase the absorption of acoustic energy and accelerate heating. However, formation of microbubbles within the tumor tissue remains a challenge. Phase-shift nanoemulsions (PSNE) have been developed as a means for producing microbubbles within tumors. PSNE are emulsions of submicron-sized, lipid-coated, and liquid perfluorocarbon droplets that can be vaporized into microbubbles using short (<1 ms), high-amplitude (>5 MPa) acoustic pulses. In this study, the impact of vaporized phase-shift nanoemulsions on the time and acoustic power required for HIFU-mediated thermal lesion formation was investigated in vitro. Methods PSNE containing dodecafluoropentane were produced with narrow size distributions and mean diameters below 200 nm using a combination of sonication and extrusion. PSNE was dispersed in albumin-containing polyacrylamide gel phantoms for experimental tests. Albumin denatures and becomes opaque at temperatures above 58°C, enabling visual detection of lesions formed from denatured albumin. PSNE were vaporized using a 30-cycle, 3.2-MHz, at an acoustic power of 6.4 W (free-field intensity of 4,586 W/cm2) pulse from a single-element, focused high-power transducer. The vaporization pulse was immediately followed by a 15-s continuous wave, 3.2-MHz signal to induce ultrasound-mediated heating. Control experiments were conducted using an identical procedure without the vaporization pulse. Lesion formation was detected by acquiring video frames during sonication and post-processing the images for analysis. Broadband emissions from inertial cavitation (IC) were passively detected with a focused, 2-MHz transducer. Temperature measurements were acquired using a needle thermocouple. Results Bubbles formed at the HIFU focus via

  1. Antimicrobial Activity of Nanoemulsion on Cariogenic Planktonic and Biofilm Organisms

    PubMed Central

    Amaechi, Bennett T.; Rawls, H Ralph; Valerie, A Lee

    2011-01-01

    Introduction Nanoemulsions (NE) are a unique class of disinfectants produced by mixing a water immiscible liquid phase into an aqueous phase under high shear forces. NE have antimicrobial properties and are also effective anti-biofilm agents. Materials and Methods The effectiveness of nanoemulsion and its components was determined against Streptococcus mutans and Lactobacillus casei by live/dead staining. In vitro antimicrobial effectiveness of nanoemulsion against planktonic Streptococcus mutans, Lactobacillus casei, Actinomyces viscosus, Candida albicans and mixed culture was determined by a serial dilution technique to obtain minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC). In addition, efficacy was investigated by kinetics of killing, adherence and biofilm assays. Results Compared to its components, nanoemulsion showed notable antimicrobial activity against biofilm organisms, up to 83.0% kill within 1 min. NE dilutions ranging from 243 to 19683 were effective against planktonic S. mutans, L. casei, A. viscosus, C. albicans and mixed culture of these four strains as shown through MIC/MBC assays. NE showed antimicrobial activity against planktonic cells at high dilutions, confirmed by time kill studies. The level of adhesion on glass surface was reduced by 94.2 to 99.5 % in nanoemulsion treated groups (p < 0.001). 4-day-old S. mutans, L. casei, A. viscosus, C. albicans and mixed cultures biofilms treated with NE showed reductions of bacterial counts with decreasing dilutions (p < 0.001). Conclusion These results suggest that nanoemulsion has effective anti-cariogenic activity against cariogenic microorganisms and may be a useful medication in the prevention of caries. PMID:21807359

  2. Lipolytic efficacy of alginate double-layer nanoemulsion containing oleoresin capsicum in differentiated 3T3-L1 adipocytes.

    PubMed

    Lee, Mak-Soon; Jung, Sunyoon; Shin, Yoonjin; Lee, Seohyun; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2017-01-01

    Background: Oleoresin capsicum (OC) is an organic extract from fruits of the genus Capsicum, and has been reported to have an anti-obesity effect. Objective: This study comparatively investigated lipolytic effects of single-layer nanoemulsion (SN) and alginate double-layer nanoemulsion (AN) containing OC in 3T3-L1 adipocytes. Methods: SN and AN were compared by analyzing the intracellular lipid accumulation, triglyceride (TG) content, release of free fatty acids (FFAs) and glycerol, and mRNA expression of genes related to adipogenesis and lipolysis were analyzed in fully differentiated 3T3-L1 adipocytes. Results: Compared with SN, AN exhibited higher efficiency in inhibiting the intracellular lipid accumulation and TG content, and enhanced the release of FFAs and glycerol into the medium. In AN-treated cells, mRNA levels of peroxisome proliferator-activated receptor-γ and the fatty acid-binding protein adipocyte protein-2, which are involved in adipogenesis, were down-regulated, whereas those of genes related to lipolysis, including hormone-sensitive lipase and carnitine palmitoyl transferase-1α, were up-regulated compared with SN-treated cells. Conclusion: The lipolytic effect of AN was greater than that of SN; this was partly associated with the increased TG hydrolysis via induction of lipolytic gene expression and suppression of adipogenic gene expression in 3T3-L1 adipocytes.​​​​.

  3. A new method for the formulation of double nanoemulsions.

    PubMed

    Ding, Shukai; Anton, Nicolas; Akram, Salman; Er-Rafik, Meriem; Anton, Halina; Klymchenko, Andrey; Yu, Wei; Vandamme, Thierry F; Serra, Christophe A

    2017-02-22

    Double emulsions are very attractive systems for many reasons; the most important of these are their capacity to encapsulate hydrophilic and lipophilic molecules simultaneously in a single particle and their potentiality to protect fragile hydrophilic molecules from the continuous phase. Double emulsions represent a technology that is widely present down to the micrometer scale; however, double nanoemulsions, with their new potential applications as nanomedicines or diagnosis agents, currently present a significant challenge. In this study, we propose an original two-step approach for the fabrication of double nanoemulsions with a final size below 200 nm. The process consists of the formulation of a primary water-in-oil (w1/O) nanoemulsion by high-pressure homogenization, followed by the re-emulsification of this primary emulsion by a low-energy method to preserve the double nanostructure. Various characterization techniques were undertaken to confirm the double structure and to evaluate the encapsulation efficiency of a small hydrophilic probe in the inner aqueous droplets. Complementary fluorescence confocal and cryo-TEM microscopy experiments were conducted to characterize and confirm the double structure of the double nanoemulsion.

  4. Design and Development of Nanoemulsion Systems Containing Interferon Gamma.

    PubMed

    Ribeiro, Elton B; Honorio-França, Adenilda C; França, Eduardo L; Soler, Maria A G

    2016-01-01

    The aim of this study was to design and develop stable nanoemulsion formulations containing IFN-γ to probe their use as an immunomodulating agent. The nanoemulsions comprising distilled water, triglycerides of capric acid/caprylic, sobitan-oleate (SP), polysorbate 80 (TW) and propylene glycol (PG) were prepared through ultra-homogenization and characterized regarding droplet size, polydispersity, surface charge, preliminary and accelerated physical stability, and rheological properties. Stable nanoemulsions were selected to incorporate nano doses of IFN-γ (100 ng.mL-1). The influence of IFN-γ incorporated nanoemulsions on functional activity of mononuclear cell for Escherichia coli enteropathogenic was analyzed through superoxide release, phagocytosis, microbicidal activity and intracellular calcium release. The optimized formulation, comprising aqueous and oily phase of 10 % and 80 %, respectively, and surfactant mix ratio (SP/TW/PG) of 3.5/5.5/1.0, remained stable in extreme conditions during 90 days, displaying oil-in-water characteristics, biocompatible pH value, significant maintenance of its rheological profile, hydrodynamic radius of 205 nm, zeta potential of -40 mV and average dose of IFN-γ 91 ng.mL- The developed formulation did not alter the MN cell viability rates. Increased the superoxide release, phagocytosis index and intracellular calcium release of MN cells of human blood. Our findings indicate that the produced formulation improved the immunomodulatory activity of the IFN-γ.

  5. NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging

    PubMed Central

    O’Hanlon, Claire E.; Amede, Konjit G.; O’Hear, Meredith R.; Janjic, Jelena M.

    2012-01-01

    Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, 19F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a 19F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180 nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2 mg/mL. The reported nanoemulsion’s properties, including small particle size, visibility under 19F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment. PMID:22675234

  6. Characterization of rice bran wax policosanol and its nanoemulsion formulation.

    PubMed

    Ishaka, Aminu; Umar Imam, Mustapha; Mahamud, Rozi; Zuki, Abu Bakar Zakaria; Maznah, Ismail

    2014-01-01

    Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects; however, it has a bioavailability of less than 10%. Therefore, there is a need to improve its bioavailability, and one of the ways of doing this is by nanoemulsion formulation. Different droplet size distributions are usually achieved when emulsions are formed, which solely depends on the preparation method used. Mostly, emulsions are intended for better delivery with maintenance of the characteristics and properties of the leading components. In this study, policosanol was extracted from rice bran wax, its composition was determined by gas chromatography mass spectrophotometry, nanoemulsion was made, and the physical stability characteristics were determined. The results showed that policosanol nanoemulsion has a nanosize particle distribution below 100 nm (92.56-94.52 nm), with optimum charge distribution (-55.8 to -45.12 mV), pH (6.79-6.92) and refractive index (1.50); these were monitored and found to be stable for 8 weeks. The stability of policosanol nanoemulsion confers the potential to withstand long storage times.

  7. Development of an insecticidal nanoemulsion with Manilkara subsericea (Sapotaceae) extract

    PubMed Central

    2014-01-01

    Background Plants have been recognized as a good source of insecticidal agents, since they are able to produce their own defensives to insect attack. Moreover, there is a growing concern worldwide to develop pesticides with low impact to environment and non-target organisms. Hexane-soluble fraction from ethanolic crude extract from fruits of Manilkara subsericea and its triterpenes were considered active against a cotton pest (Dysdercus peruvianus). Several natural products with insecticidal activity have poor water solubility, including triterpenes, and nanotechnology has emerged as a good alternative to solve this main problem. On this context, the aim of the present study was to develop an insecticidal nanoemulsion containing apolar fraction from fruits of Manilkara subsericea. Results It was obtained a formulation constituted by 5% of oil (octyldodecyl myristate), 5% of surfactants (sorbitan monooleate/polysorbate 80), 5% of apolar fraction from M. subsericea and 85% of water. Analysis of mean droplet diameter (155.2 ± 3.8 nm) confirmed this formulation as a nanoemulsion. It was able to induce mortality in D. peruvianus. It was observed no effect against acetylcholinesterase or mortality in mice induced by the formulation, suggesting the safety of this nanoemulsion for non-target organisms. Conclusions The present study suggests that the obtained O/A nanoemulsion may be useful to enhance water solubility of poor water soluble natural products with insecticidal activity, including the hexane-soluble fraction from ethanolic crude extract from fruits of Manilkara subsericea. PMID:24886215

  8. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion.

    PubMed

    Abdou, Ebtsam M; Kandil, Soha M; Miniawy, Hala M F El

    2017-08-30

    Zolmitriptan (ZT) is a well-tolerated drug in migraine treatment suffering from low bioavailability due to low amount of the drug that reaches the brain after oral and nasal delivery. Development of new nasal mucoadhesive nanoemulsion formulation for zolmitriptan may success in delivering the drug directly from the nose to the brain to achieve rapid onset of action and high drug concentration in the brain which is required for treatment of acute migraine. ZT mucoadhesive nanoemulsion were prepared and characterized for drug content, zeta potential, particle size, morphology, residence time and permeation through the nasal mucosa. The selected formula was tested in-vivo in mice for its pharmacokinetics in comparison with intravenous and nasal solution of zolmitriptan. Results showed that addition of chitosan as mucoadhesive agent in 0.3% concentration to the nanoemulsion enhanced its residence time and zetapotential with no significant effect on the globule size. All tested formulations showed higher permeability coefficients than the zolmitriptan solution through the nasal mucosa. In-vivo studies showed that the mucoadhesive nanoemulsion formulation of zolmitriptan has higher AUC0-8 and shorter Tmax in the brain than the intravenous or the nasal solution. This was related to the small globule size and higher permeability of the formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Essential oil nanoemulsions as antimicrobial agents in food.

    PubMed

    Donsì, Francesco; Ferrari, Giovanna

    2016-09-10

    The crescent interest in the use of essential oils (EOs) as natural antimicrobials and preservatives in the food industry has been driven in the last years by the growing consumers' demand for natural products with improved microbial safety, and fresh-like organoleptic properties. Nanoemulsions efficiently contribute to support the use of EOs in foods by increasing their dispersibility in the food areas where microorganisms grow and proliferate, by reducing the impact on the quality attributes of the product, as well as by enhancing their antimicrobial activity. Understanding how nanoemulsions intervene on the mass transfer of EOs to the cell membrane and on the mechanism of antimicrobial action will support the engineering of more effective delivery systems and foster the application of EOs in real food systems. This review focuses on the enabling contribution of nanoemulsions to the use of EOs as natural preservative agents in food, (a) specifically addressing the formulation and fabrication of stable EO nanoemulsions, (b) critically analyzing the reported antimicrobial activity data, both in vitro and in product, to infer the impact of the delivery system on the mechanisms of action of EOs, as well as (c) discussing the regulatory issues associated with their use in food systems.

  10. Characterization of rice bran wax policosanol and its nanoemulsion formulation

    PubMed Central

    Ishaka, Aminu; Umar Imam, Mustapha; Mahamud, Rozi; Zuki, Abu Bakar Zakaria; Maznah, Ismail

    2014-01-01

    Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects; however, it has a bioavailability of less than 10%. Therefore, there is a need to improve its bioavailability, and one of the ways of doing this is by nanoemulsion formulation. Different droplet size distributions are usually achieved when emulsions are formed, which solely depends on the preparation method used. Mostly, emulsions are intended for better delivery with maintenance of the characteristics and properties of the leading components. In this study, policosanol was extracted from rice bran wax, its composition was determined by gas chromatography mass spectrophotometry, nanoemulsion was made, and the physical stability characteristics were determined. The results showed that policosanol nanoemulsion has a nanosize particle distribution below 100 nm (92.56–94.52 nm), with optimum charge distribution (−55.8 to −45.12 mV), pH (6.79–6.92) and refractive index (1.50); these were monitored and found to be stable for 8 weeks. The stability of policosanol nanoemulsion confers the potential to withstand long storage times. PMID:24872689

  11. The preparation of 3,5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release.

    PubMed

    Zhang, Yue; Gao, Jungang; Zheng, Hetang; Zhang, Ran; Han, Yucui

    2011-01-01

    We have reported a novel procedure to prepare 3,5-dihydroxy-4-isopropylstilbene (DHPS) nanoemulsion, using a low-energy emulsification method. Based on the phase diagram, the optimum prescription of nanoemulsion preparation was screened. With polyoxyethylenated castor oil (EL-40) as the surfactant, ethanol as the co-surfactant, and isopropyl myristate (IPM) as the oil phase, the DHPS nanoemulsion was obtained with a transparent appearance, little viscosity, and spherically uniform distribution verified by transmission electron microscopy and laser scattering analyzer. The nanoemulsion was also determined by FT-Raman spectroscopy. The DHPS nanoemulsion demonstrated good stability and stable physical and chemical properties. The nanoemulsion dramatically improved the transdermal release of DHPS (from 8.02 μg · cm(-2) to 273.15 μg · cm(-2)) and could become a favorable new dosage form for DHPS.

  12. The preparation of 3,5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release

    PubMed Central

    Zhang, Yue; Gao, Jungang; Zheng, Hetang; Zhang, Ran; Han, Yucui

    2011-01-01

    We have reported a novel procedure to prepare 3,5-dihydroxy-4-isopropylstilbene (DHPS) nanoemulsion, using a low-energy emulsification method. Based on the phase diagram, the optimum prescription of nanoemulsion preparation was screened. With polyoxyethylenated castor oil (EL-40) as the surfactant, ethanol as the co-surfactant, and isopropyl myristate (IPM) as the oil phase, the DHPS nanoemulsion was obtained with a transparent appearance, little viscosity, and spherically uniform distribution verified by transmission electron microscopy and laser scattering analyzer. The nanoemulsion was also determined by FT-Raman spectroscopy. The DHPS nanoemulsion demonstrated good stability and stable physical and chemical properties. The nanoemulsion dramatically improved the transdermal release of DHPS (from 8.02 μg · cm−2 to 273.15 μg · cm−2) and could become a favorable new dosage form for DHPS. PMID:21674020

  13. Molecular characterization of water and surfactant AOT at nanoemulsion surfaces.

    PubMed

    Hensel, Jennifer K; Carpenter, Andrew P; Ciszewski, Regina K; Schabes, Brandon K; Kittredge, Clive T; Moore, Fred G; Richmond, Geraldine L

    2017-07-31

    Nanoemulsions and microemulsions are environments where oil and water can be solubilized in one another to provide a unique platform for many different biological and industrial applications. Nanoemulsions, unlike microemulsions, have seen little work done to characterize molecular interactions at their surfaces. This study provides a detailed investigation of the near-surface molecular structure of regular (oil in water) and reverse (water in oil) nanoemulsions stabilized with the surfactant dioctyl sodium sulfosuccinate (AOT). Vibrational sum-frequency scattering spectroscopy (VSFSS) is used to measure the vibrational spectroscopy of these AOT stabilized regular and reverse nanoemulsions. Complementary studies of AOT adsorbed at the planar oil-water interface are conducted with vibrational sum-frequency spectroscopy (VSFS). Jointly, these give comparative insights into the orientation of interfacial water and the molecular characterization of the hydrophobic and hydrophilic regions of AOT at the different oil-water interfaces. Whereas the polar region of AOT and surrounding interfacial water molecules display nearly identical behavior at both the planar and droplet interface, there is a clear difference in hydrophobic chain ordering even when possible surface concentration differences are taken into account. This chain ordering is found to be invariant as the nanodroplets grow by Ostwald ripening and also with substitution of different counterions (Na:AOT, K:AOT, and Mg:AOT) that consequently also result in different sized nanoparticles. The results paint a compelling picture of surfactant assembly at these relatively large nanoemulsion surfaces and allow for an important comparison of AOT at smaller micellar (curved) and planar oil-water interfaces.

  14. Eugenol-loaded antimicrobial nanoemulsion preserves fruit juice against, microbial spoilage.

    PubMed

    Ghosh, Vijayalakshmi; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-02-01

    Oil-in-water nanoemulsion was formulated using sesame oil, non-ionic surfactant (Tween20/Tween80) and water by ultrasound cavitation method. Development of nanoemulsion was optimized for process parameters such as surfactant type, surfactant concentration and emulsification time to obtain lower droplet diameter with greater stability. Increase in surfactant concentration and emulsification time resulted in nanoemulsion with minimized droplet diameter. Tween80 was more effective in reducing droplet size when compared to that of Tween20. Selected formulation with optimized process parameter (with oil-surfactant mixing ratio of 1:3 v/v and Tween80 as surfactant) was used for delivery of eugenol. Eugenol-loaded nanoemulsion was formulated with droplet diameter of 13 nm and was stable for more than 1 month. Sesame oil blended eugenol-loaded nanoemulsion demonstrated lower droplet size and higher stability than only-eugenol (without sesame oil) nanoemulsion. Eugenol-loaded nanoemulsion S3E3 exhibited antibacterial activity against Staphylococcus aureus. Inactivation kinetics of S. aureus showed time and concentration killing of bacteria upon treatment with S3E3 nanoemulsion. Fluorescence microscopy results demonstrated that S3E3 nanoemulsion treatment resulted in alteration of membrane permeability. In situ assessment of S3E3 in orange juice exhibited a significant reduction in the native bacteria population. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Nanoemulsion of eucalyptus oil and its larvicidal activity against Culex quinquefasciatus.

    PubMed

    Sugumar, S; Clarke, S K; Nirmala, M J; Tyagi, B K; Mukherjee, A; Chandrasekaran, N

    2014-06-01

    Filariasis is a mosquito-borne disease that causes lymphedema and the main vector is Culex quinquefasciatus. A simple measure was taken to eradicate the vector using nanoemulsion. Eucalyptus oil nanoemulsion was formulated in various ratios comprising of eucalyptus oil, tween 80 and water by ultrasonication. The stability of nanoemulsion was observed over a period of time and 1:2 ratios of eucalyptus oil (6%) and surfactant (12%) was found to be stable. The formulated eucalyptus oil nanoemulsion was characterized by transmission electron microscopy and dynamic light scattering. The nanoemulsion droplets were found to have a Z-average diameter of 9.4 nm and were spherical in shape. The larvicidal activity of eucalyptus oil nanoemulsion and bulk emulsion was tested and compared. Our nanoemulsion showed higher activity when compared to bulk emulsion. The histopathology of larvae-treated and untreated nanoemulsion was analyzed. Furthermore, biochemical assays were carried out to examine the effect of nanoemulsion on biochemical characteristics of larvae. The treated larval homogenate showed decrease in total protein content and a significant reduction in the levels of acetylcholinesterase. The levels of acid and alkaline phosphatase also showed reduction as compared to control larval homogenate.

  16. Phase Change Characteristics of a Nanoemulsion as a Latent Heat Storage Material

    NASA Astrophysics Data System (ADS)

    Fumoto, Koji; Sato, Noriaki; Kawaji, Masahiro; Kawanami, Tsuyoshi; Inamura, Takao

    2014-10-01

    The primary objective of this study was to investigate the fundamental phase change characteristics of a nanoemulsion using differential scanning calorimetry (DSC). Tetradecane, which has a slightly higher melting point than water, was utilized as the phase change material for the nanoemulsion. The melting point of the nanoemulsion, the melting peak temperature, and latent heat were examined in detail. Regarding the fundamental phase change characteristics of the nanoemulsion, it was found that its phase change characteristics were strongly affected by the temperature-scanning rate of the DSC. Moreover, it was confirmed that the phase change behavior does not change with repeated solidification and melting.

  17. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether.

    PubMed

    Laxmi, Moksha; Bhardwaj, Ankur; Mehta, Shuchi; Mehta, Abhinav

    2015-01-01

    The present study aimed to develop a kinetically stable nanoemulsion of artemether with improved solubility, stability and oral bioavailability. Nanoemulsion was prepared by ultrasonication technique using internal oil phase (consisted of the drug dissolved in coconut oil and span 80) and external phase (comprising tween 80 and ethanol dissolved in water). The formulations were optimized using various parameters like percentage transmittance, refractive index, drug content, viscosity, zeta potential and release rate. Stability studies were conducted for a period of 90 days using stability chambers. In vivo studies of the developed formulations were conducted on Wistar rats and data were analyzed statistically. The nanoemulsion as observed under transmission electron microscope were found to be spherical in shape with an average size of 79.0 nm and a zeta potential of -15 mV which indicated of good electrokinetic stability of nanoemulsion . Nanoemulsion was found to be clear and transparent in appearance with a percentage transmittance of 98.2. Refractive index of 1.32 of the nanoemulsion indicated the isotropic nature of the drug. Release rate of the drug from the nanoemulsion formulation was found to be quite significant (P < 0.001) as compared to the plain drug. In vivo oral bioavailability of the nanoemulsion formulation was found to be 2.6-fold higher than the plain drug (˜ 40%) as observed from pharmacokinetic studies. Thus it was observed that nanoemulsion proved itself as a promising alternate for improving the bioavailability of artemether.

  18. Exotic Vegetable Oils for Cosmetic O/W Nanoemulsions: In Vivo Evaluation.

    PubMed

    Pereira, Tatiana A; Guerreiro, Carolina M; Maruno, Monica; Ferrari, Marcio; Rocha-Filho, Pedro Alves

    2016-02-24

    Oil-in-water nanoemulsions are stable systems with droplet sizes in the 20-200 nm range. The physicochemical properties of these systems may be influenced by the addition of additives. Thus, the influence of ethoxylated (EL) and acetylated lanolin (AL) addition on the droplet size, pH values, electrical conductivity and stability of nanoemulsions was investigated. Then, effect of nano-emulsions additives with EL (NE-EL) or AL (NE-AL) in hydration, oiliness and pH of the skin were evaluated. Nanoemulsion safety was evaluated through the observation of no undesirable effects after skin formulation application. Both additives caused changes in droplet size and electrical conductivity, but not in pH values. Nanoemulsions containing up to 6.0% ethoxylated lanolin and 2.0% acetylated lanolin remained stable after centrifugation tests. Higher concentrations of the additives made the nanoemulsions unstable. Stability tests showed that ethoxylated lanolin produced more stable nanoemulsions then acetylated lanolin and that the major instability phenomenon occurring in these systems is coalescence at elevated temperatures. Nanoemulsion-based lanolin derivatives increased skin hydration and oiliness and did not change cutaneous pH values. These formulations are non-toxic since they did not cause any irritation on the skin surface after nanoemulsion application, showing potential as carriers for pharmaceuticals and cosmetic applications.

  19. Development of food-grade nanoemulsions and emulsions for delivery of omega-3 fatty acids: opportunities and obstacles in the food industry.

    PubMed

    Walker, Rebecca; Decker, Eric A; McClements, David Julian

    2015-01-01

    Consumption of biologically active amounts of omega-3 fatty acids is linked to improved human health, which has partly been attributed to their important role in brain development and cardiovascular health. Western diets are relatively low in omega-3 fatty acids and many consumers turn to supplements or functional foods to increase their intake of these healthy lipids. Fish oil is one of the most widely used sources of omega-3 fatty acid for supplementation and has greater health benefits than plant sources because of its higher concentration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The incorporation of omega-3 fatty acids into foods and beverages is often challenging due to their low water-solubility, poor oxidative stability, and variable bioavailability. Nanoemulsions offer a promising way to incorporate omega-3 fatty acids into liquid food systems like beverages, dressing, sauces, and dips. Nanoemulsions are colloidal dispersions that contain small oil droplets (r<100 nm) that may be able to overcome many of the challenges of fortifying foods and beverages with omega-3 fatty acids. The composition and fabrication of nanoemulsions can be optimized to increase the chemical and physical stability of oil droplets, as well as to increase the bioavailability of omega-3 fatty acids.

  20. Physical properties of a frozen yogurt fortified with a nano-emulsion containing purple rice bran oil

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were to develop and evaluate a frozen yogurt (FY) fortified with a nano-emulsion containing purple rice bran oil (NPRBO). A nano-emulsion with a droplet size range of 150-300 nm was produced by sonication followed by ultra-shear homogenization. The nano-emulsion was mi...

  1. Nano-emulsions and nanocapsules by the PIT method: an investigation on the role of the temperature cycling on the emulsion phase inversion.

    PubMed

    Anton, Nicolas; Gayet, Pascal; Benoit, Jean-Pierre; Saulnier, Patrick

    2007-11-01

    This paper focuses on the phenomenological understanding of temperature cycling process, applied to the phase inversion temperature (PIT) method. The role of this particular thermal treatment on emulsions phase inversion, as well as its ability to generate nano-emulsions have been investigated. In order to propose a general study, we have based our investigations on a given formulation of nano-emulsions classically proposed in the literature [Heurtault, B., Saulnier, P., Pech, B., Proust, J. E., Benoit, J.P., 2002. A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharm. Res. 19, 875; Lamprecht, A., Bouligand, Y, Benoit, J.P., 2002. New lipid nanocapsules exhibit sustained release properties for amiodarone. J. Control. Release 84, 59-68], using a polyethoxylated model nonionic surfactant, a polyoxyehtylene-660-12-hydroxy stearate, stabilizing the emulsion composed of caprilic triglycerides (triglycerides medium chains), salt water (and also phospholipidic amphiphiles neutral for the formulation). Characterization of nano-emulsions was performed by dynamic light scattering (DLS) which provides the hydrodynamic diameter, but also the polydispersity index (PDI), as a fundamental criteria to judge the quality of the dispersion. Another aspect of the characterization was done following the emulsion inversion and structure by electrical conductivity through the temperature scan. Overall, the role such a temperature cycling process on the formulation of nano-emulsions appears to be relatively important, and globally enhanced as the surfactant concentration is lowered. Actually, both the hydrodynamic diameter and the PDI decrease as a function of the number and temperature cycles up to stabilize a steady state. Eventually, such a cycling process allows the generation of nano-emulsions in ranges of compositions largely expanded when compared with the classical PIT method. These general and interesting trends emerge from the results, are

  2. Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for enhanced topical delivery of ibuprofen

    PubMed Central

    Salim, Norazlinaliza; Basri, Mahiran; Rahman, Mohd BA; Abdullah, Dzulkefly K; Basri, Hamidon

    2012-01-01

    Introduction During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied. Methods A palm kernel oil esters nanoemulsion was modified with different hydrocolloid gums for the topical delivery of ibuprofen. Three different hydrocolloids (gellan gum, xanthan gum, and carrageenan) were selected for use. Ternary phase diagrams were constructed using palm kernel oil esters as the oil, Tween 80 as the surfactant, and water. Nanoemulsions were prepared by phase inversion composition, and were gradually mixed with the freshly prepared hydrocolloids. The initial nanoemulsion and modified nanoemulsions were characterized. The abilities of the nanoemulsions to deliver ibuprofen were assessed in vitro, using a Franz diffusion cell fitted with rat skin. Results No significant changes were observed in droplet size (~16–20 nm) but a significant difference in polydispersity indexes were observed before and after the modification of nanoemulsions using gellan gum, carrageenan, and xanthan gum. The zeta potentials of the initial nanoemulsions (−11.0 mV) increased to −19.6 mV, −13.9 mV, and −41.9 mV, respectively. The abilities of both the initial nanoemulsion (T802) and the modified nanoemulsion to deliver ibuprofen through the skin were evaluated in vitro, using Franz diffusion cells fitted with rat skin. The in vitro permeation data showed that the modified nanoemulsion (Kp value of 55.4 × 10−3 cm · h−1) increased the permeability of ibuprofen 4.40 times over T802 (Kp value of 12.6 × 10−3 cm · h−1) (P < 0.05). Conclusion The

  3. Relation of Resemblance in Information Retrieval.

    ERIC Educational Resources Information Center

    Pietilainen, Pirkko

    1982-01-01

    Presents a method for using the amount of semantic information in search-query terms as a weighting factor in constructing a fuzzy relation of resemblance between retrieved items in information retrieval online. Two tables, two figures, and a reference list accompany the text. (Author/JL)

  4. Q10-loaded NLC versus nanoemulsions: stability, rheology and in vitro skin permeation.

    PubMed

    Junyaprasert, Varaporn B; Teeranachaideekul, Veerawat; Souto, Eliana B; Boonme, Prapaporn; Müller, Rainer H

    2009-07-30

    In this study, nanoemulsions (NE) of medium chain triacylglycerols (MCT) and nanostructured lipid carriers (NLC) of cetyl palmiate/MCT were produced to load coenzyme Q(10) (Q(10)) and characterized for their stability before and after incorporation into xanthan gum hydrogels. After storage at 4, 25 and 40 degrees C, the particles remained in the nanosize range for 12 months, with zeta potential higher than |40 mV|. Similar results were found in xanthan gum-based hydrogels containing NE or NLC. The crystallinity index of Q(10)-loaded NLC increased after being incorporated into hydrogels. The Q(10) entrapped in NLC and NE remained higher than 90% at all temperatures for 12 months but dramatically decreased when exposed to light. From the rheological studies, both NLC and NE dispersions possessed pseudoplastic flow having more liquid characteristics, whereas NLC and NE hydrogels exhibited plastic flow with thixothopy, showing more elastic rather than viscous properties. The occurrence of a spatial arrangement of lipid molecules was observed in the matrix of NLC when entrapped into hydrogels. From in vitro permeation studies, it could be stated that the amount of Q(10) released and occlusiveness were major keys to promote the deep penetration of Q(10) into the skin.

  5. Paclitaxel associated with cholesterol-rich nanoemulsions promotes atherosclerosis regression in the rabbit.

    PubMed

    Maranhão, Raul C; Tavares, Elaine R; Padoveze, Amanda F; Valduga, Claudete J; Rodrigues, Debora G; Pereira, Maria D

    2008-04-01

    A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drugs against those cells. The current study was designed to verify in rabbits whether LDE concentrates in the lesioned rabbit artery and whether a paclitaxel derivative, paclitaxel oleate, associated to LDE could reduce the atherosclerotic lesions. Sixteen male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 under cholesterol feeding, eight animals were treated with four weekly intravenous injections of LDE-paclitaxel (4 mg/kg) and eight with four weekly intravenous saline solution injections for additional 30 days. On day 60, the animals were sacrificed for analysis. The uptake of LDE labeled with [(14)C]-cholesteryl oleate by the aortic arch of cholesterol-fed rabbits was twice as much that observed in animals fed only regular chow. LDE-paclitaxel reduced the lesion areas of cholesterol-fed animals by 60% and intima-media ratio fourfold and inhibited the macrophage migration and the smooth muscle cell proliferation and invasion of the intima. LDE-paclitaxel treatment had no toxicity. In conclusion, LDE-paclitaxel produced pronounced atherosclerosis regression without toxicity and has shown remarkable potential in cardiovascular therapeutics.

  6. Nanoemulsion-based mucosal adjuvant induces apoptosis in human epithelial cells

    PubMed Central

    Orzechowska, Beata U.; Kukowska-Latallo, Jolanta F.; Coulter, Alexa D.; Szabo, Zsuzsanna; Gamian, Andrzej; Myc, Andrzej

    2015-01-01

    Nanoemulsions (NEs) are adjuvants that enhance antigen penetration of the nasal mucosa, increase cellular uptake of antigens by both epithelial and dendritic cells, and promote the migration of antigen-loaded dendritic cells to regional lymph nodes within 24-hours of vaccine administration. The objective of this study was to elucidate cell death caused by W805EC NE and identify caspases and genes associated with death pathways. Consistent with this aim, we show that exposure of human epithelial cells (EC), both RPMI 2650 and FaDu, to NE results in the activation of caspases (1, 3/7, 6, 8, and 9) and the expression of genes involved in apoptotic as well as authophagy and necrosis pathways. Interestingly, the NE activates caspase 8 which promotes “immunogenic apoptosis”. The rescue assay was employed to investigate the fate of RPMI 2650 cells treated with W805EC NE. After four hour treatment with as little as 0.03% of NE no cells were rescued at 72 hours. Remarkably, immediately after four-hour treatment, the cells morphologically resembled untreated cells and most of the cells were alive. Altogether, these results suggest that NE induces death of human ECs through multiple pathways. Epithelial cell death caused by W805EC may have further implications on antigen uptake, processing, and presentation by DC's. PMID:25817825

  7. Enhanced antibacterial effects of clove essential oil by nanoemulsion.

    PubMed

    Anwer, Md Khalid; Jamil, Shahid; Ibnouf, Elmutasim Osman; Shakeel, Faiyaz

    2014-01-01

    The aim of present study was to develop and evaluate nanoemulsion formulations of clove essential oil (CEO) for its antibacterial effects in comparison with pure CEO and standard amikacin antibiotic (positive control). Different nanoemulsions of CEO were developed by aqueous phase titration method via construction of pseudo-ternary phase diagrams and investigated for thermodynamic stability and self-nanoemulsification tests. Selected formulations (F1-F5) were characterized for droplet size distribution, viscosity, zeta potential, transmittance and surface morphology. Based on lowest droplet size (29.1 nm), lowest PI (0.026), lowest viscosity (34.6 cp), optimal zeta potential (-31.4 mV), highest transmittance (99.4 %) and lowest concentration of Triacetin (8 % w/w), CEO nanoemulsion F1 (containing 1 % w/w of CEO, 8 % w/w of Triacetin, 15 % w/w of Tween-80, 15 % w/w of Labrasol and 61 % w/w of water) was subjected to antibacterial studies in comparison with pure oil and standard amikacin. The antibacterial effects of F1 were found to be superior over pure oil against all bacterial strains investigated. However, the antibacterial effects of F1 were highly comparable with standard amikacin against all bacterial strains. The minimum inhibitory concentrations (MICs) of F1 were observed in the range of 0.075-0.300 % w/w as compared to pure oil (MICs 0.130-0.500 % w/w) and standard amikacin (MICs 2-16 μg/ml). These results indicated the potential of nanoemulsions for enhancing the therapeutic efficacy of natural bioactive ingredients such as CEO.

  8. Emulsion versus nanoemulsion: how much is the formulative shift critical for a cosmetic product?

    PubMed

    Musazzi, Umberto M; Franzè, Silvia; Minghetti, Paola; Casiraghi, Antonella

    2017-05-15

    The use of nanoemulsions in cosmetic products has been enlarged in the last decades because of several formulative advantages (e.g., the improved self-life stability, better texture properties). In addition, nanoemulsions seemed to improve the penetration of active ingredients through the human skin, comparing to conventional emulsion. In this contest, the risk of a higher systemic exposure of consumer to active ingredients, due to the ability of nanoemulsion to enhance permeation, results a critical attribute that should be evaluated for assuring the consumer safety. The aim of this work was the evaluation of how an oil-in-water (O/W) nanoemulsion can influence the in vitro skin permeation profiles of two model active ingredients with different polarity (i.e., caffeine and ethyl ximenynate). Preliminarily, since both selected molecules influenced the physical stability of nanoemulsion, formulative studies were carried out to identify the most stable formulation to perform in vitro permeation studies. The overall results demonstrated that nanoemulsions could significantly influence the permeation profiles of molecules as a function of their physicochemical properties. In particular, O/W nanoemulsions significantly improved the permeation profiles of apolar active ingredients in comparison to conventional emulsions, whereas no differences were observable for polar molecules. Considering such findings, it is worth observing that there is room for reconsidering the risk assessment of nanoemulsion-based cosmetic products.

  9. Nanoemulsion-based gel formulations of COX-2 inhibitors for enhanced efficacy in inflammatory conditions

    NASA Astrophysics Data System (ADS)

    Lala, R. R.; Awari, N. G.

    2013-01-01

    In the present study, we have investigated the potential of a nanoemulsion (thermodynamically stable transparent dispersions of oil and water having a droplet size <200 nm) formulation for the topical delivery of COX-2 inhibitors using etoricoxib as a model drug. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudo-ternary phase diagrams. The prepared nanoemulsions were subjected to thermodynamic stability testing. Those that passed these tests were characterized for viscosity, droplet size and differential scanning calorimetry. Topical permeation of etoricoxib through porcine abdominal skin was estimated using the Franz diffusion cell. The ex vivo skin permeation profile of optimized formulations was compared with that of etoricoxib conventional gel. A significant increase in permeability was observed in optimized nanoemulsion formulations consisting of 2 % w/w of etoricoxib, 20 % w/w of Triacetin, 38 % w/w of a surfactant mixture (Cremophor RH 40:Transcutol P), and 42 % w/w of water. The anti-inflammatory effects of this formulation on carrageenan-induced paw edema in rats showed a significant increase in the percent inhibition value (84.61 % with the nanoemulsion gel and 92.30 % with the nanoemulsion) as compared with the conventional gel (69.23 %) after 6 h when compared with etoricoxib conventional gel. These results suggest that nanoemulsions can serve as potential vehicles for improved transdermal delivery of anti-inflammatory agents such as etoricoxib.

  10. Clotrimazole nanoemulsion for malaria chemotherapy. Part I: preformulation studies, formulation design and physicochemical evaluation.

    PubMed

    Borhade, Vivek; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2012-07-15

    Clotrimazole was formulated in nanoemulsion based system with the aim of improving its solubility and dissolution, which can further used for its preclinical evaluation. Clotrimazole nanoemulsion was prepared using spontaneous nanoemulsification method. Preformulation studies were preformed to evaluate drug-excipient compatibility, solution state pH stability and pH solubility profile. Solubility of clotrimazole in oils, surfactants and cosurfactants was determined to identify nanoemulsion components. Surfactants and cosurfactants were screened for their ability to emulsify selected oily phases. Phase diagrams were constructed to identify area of nanoemulsification. Influence of clotrimazole and pH of dilution medium on phase behavior were assessed. Drug-excipient chemical compatibility study facilitated to anticipate acid catalyzed degradation of clotrimazole. The pH of nanoemulsion was adjusted to 7.5, which could stabilize clotrimazole. Nanoemulsion composed of Capryol 90, Solutol HS 15 and Gelucire 44/14 enhanced solubility of clotrimazole up to 25mg/ml. The optimized clotrimazole nanoemulsion could withstand the extensive dilution and did not show any phase separation or drug precipitation. The nanoemulsion exhibited mean globule size <25 nm, which was not affected by pH of dilution medium. Dissolution profile of clotrimazole nanoemulsion in various media showed 100% drug release within 15 min irrespective of pH of medium.

  11. Neem oil (Azadirachta indica) nanoemulsion--a potent larvicidal agent against Culex quinquefasciatus.

    PubMed

    Anjali, C H; Sharma, Yamini; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2012-02-01

    Nanoemulsion composed of neem oil and non-ionic surfactant Tween 20, with a mean droplet size ranging from 31.03 to 251.43 nm, was formulated for various concentrations of the oil and surfactant. The larvicidal effect of the formulated neem oil nanoemulsion was checked against Culex quinquefasciatus. O/W emulsion was prepared using neem oil, Tween 20 and water. Nanoemulsion of 31.03 nm size was obtained at a 1:3 ratio of oil and surfactant, and it was found to be stable. The larger droplet size (251.43 nm) shifted to a smaller size of 31.03 nm with increase in the concentration of Tween 20. The viscosity of the nanoemulsion increased with increasing concentration of Tween 20. The lethal concentration (LC50) of the nanoemulsion against Cx. quinquefasciatus was checked for 1:0.30, 1:1.5 and 1:3 ratios of oil and surfactant respectively. The LC50 decreased with droplet size. The LC50 for the ratio 1:3 nanoemulsions was 11.75 mg L(-1). The formulated nanoemulsion of 31.03 nm size was found to be an effective larvicidal agent. This is the first time that a neem oil nanoemulsion of this droplet size has been reported. It may be a good choice as a potent and selective larvicide for Cx. quinquefasciatus. Copyright © 2011 Society of Chemical Industry.

  12. Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice.

    PubMed

    Ragelle, Héloïse; Crauste-Manciet, Sylvie; Seguin, Johanne; Brossard, Denis; Scherman, Daniel; Arnaud, Philippe; Chabot, Guy G

    2012-05-10

    The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antitumour activity but its administration is complicated by its low water solubility. Our aim was to incorporate fisetin into a nanoemulsion to improve its pharmacokinetics and therapeutic efficacy. Solubility and emulsification tests allowed to develop an optimal nanoemulsion composed of Miglyol 812N/Labrasol/Tween 80/Lipoid E80/water (10%/10%/2.5%/1.2%/76.3%). The nanoemulsion had an oil droplet diameter of 153 ± 2 nm, a negative zeta potential (-28.4 ± 0.6 mV) and a polydispersity index of 0.129. The nanoemulsion was stable at 4 °C for 30 days, but phase separation occurred at 20 °C. Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin. Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of fisetin and have shown that it could improve its relative bioavailability and antitumour activity. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. [Physicochemical properties and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion].

    PubMed

    Feng, Ai-Ling; Wang, Ying-Zi; Zhang, Sheng-Hai; Sun, Xiu-Yu; Duan, Fei-Peng; Li, Cai-Xia

    2013-08-01

    The research aimed at investigating the physicochemical properties, stability and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion. Prepare total alkaloids of S. flavescens nanoemulsion and detect the determination of matrine and oxymatrine in the nanoemulsion using HPLC method. Transmission electron microscopy and laser particle size analyzer were utilized to detect the shape and size of the nanoemulsion respectively. And also the stability of nanoemulsion was studied under the conditions of low temperature (4 degrees C), normal temperature (25 degrees C) and high temperature (60 degrees C). Franz diffusion cell was used to research the transdermal absorption of nanoemulsion in vitro. The results found that the nanoemulsion we prepared presented appearance of rounded, uniform; its average diameter was (15.55 +/- 2.24) nm, and particle size distribution value was 0. 161; the appearance, diameter and percentage determination of total alkaloids of S. flavescens had no variations after 15 d under 4, 25, 60 degrees C respectively. The steady-state permeation rate was 4.564 1 microg x cm(-2) x h(-1), 24 h cumulative amount of penetration was 110.7 microg x cm(-2), which was 1.86 fold of 24 h cumulative amount of aqueous solution (59.41 microg x cm(-2)). All the results demonstrated total alkaloids of S. flavescens nanoemulsion had good permeability, and could provide a new preparation for its clinical application.

  14. Excipient Nanoemulsions for Improving Oral Bioavailability of Bioactives.

    PubMed

    Salvia-Trujillo, Laura; Martín-Belloso, Olga; McClements, David Julian

    2016-01-14

    The oral bioavailability of many hydrophobic bioactive compounds found in natural food products (such as vitamins and nutraceuticals in fruits and vegetables) is relatively low due to their low bioaccessibility, chemical instability, or poor absorption. Most previous research has therefore focused on the design of delivery systems to incorporate isolated bioactive compounds into food products. However, a more sustainable and cost-effect approach to enhancing the functionality of bioactive compounds is to leave them within their natural environment, but specifically design excipient foods that enhance their bioavailability. Excipient foods typically do not have functionality themselves but they have the capacity to enhance the functionality of nutrients present in natural foods by altering their bioaccessibility, absorption, and/or chemical transformation. In this review article we present the use of excipient nanoemulsions for increasing the bioavailability of bioactive components from fruits and vegetables. Nanoemulsions present several advantages over other food systems for this application, such as the ability to incorporate hydrophilic, amphiphilic, and lipophilic excipient ingredients, high physical stability, and rapid gastrointestinal digestibility. The design, fabrication, and application of nanoemulsions as excipient foods will therefore be described in this article.

  15. Development of a Larvicidal Nanoemulsion with Pterodon emarginatus Vogel Oil

    PubMed Central

    Oliveira, Anna E. M. F. M.; Duarte, Jonatas L.; Amado, Jesus R. R.; Cruz, Rodrigo A. S.; Rocha, Clarice F.; Souto, Raimundo N. P.; Ferreira, Ricardo M. A.; Santos, Karen; da Conceição, Edemilson C.; de Oliveira, Leandra A. R.; Kelecom, Alphonse; Fernandes, Caio P.; Carvalho, José C. T.

    2016-01-01

    Pterodon emarginatus Vogel is a Brazilian species that belongs to the family Fabaceae, popularly known as sucupira. Its oil has several biological activities, including potent larvicidal property against Aedes aegypti. This insect is the vector of dengue, a tropical disease that has been considered a critical health problem in developing countries, such as Brazil. Most of dengue control methods involve larvicidal agents suspended or diluted in water and making active lipophilic natural products available is therefore considered a technological challenge. In this context, nanoemulsions appear as viable alternatives to solve this major problem. The present study describes the development of a novel nanoemulsion with larvicidal activity against A. aegypti along with the required Hydrophile Lipophile Balance determination of this oil. It was suggested that the mechanism of action might involve reversible inhibition of acetylcholinesterase and our results also suggest that the P. emarginatus nanoemulsion is not toxic for mammals. Thus, it contributes significantly to alternative integrative practices of dengue control, as well as to develop sucupira based nanoproducts for application in aqueous media. PMID:26742099

  16. Study on Tetradecane Nanoemulsion for Thermal Energy Transportation and Storage

    NASA Astrophysics Data System (ADS)

    Fumoto, Koji; Kawaji, Masahiro; Kawanami, Tsuyoshi

    Phase change emulsion (PCE) is a novel fluid used for heat storage and transfer. It has the following characteristics: higher apparent specific heat and higher heat transfer ability in the phase-change temperature range as compared to the conventional single-phase heat transfer fluids. In particular, oil-in-water (O/W) emulsions are latent heat storage materials that have low melting points, thus offering attractive opportunities for heat transfer enhancement and thermal energy transportation and storage. In this paper, milky white oil-in-water emulsions have been formed using water, Tween 80, Span 80, and tetradecane by low-energy emulsification methods (e.g., the phase inversion temperature (PIT) method). The relations between the component ratios of the emulsions and both the particle diameters and the stability of the resulting emulsions have been determined by dynamic light scattering (DLS) and vibration viscometry. The results show that the apparent viscosity of the nanoemulsion is lower than that of an emulsion, which was prepared with the same mixing ratio of surfactant and concentration of phase change material. Moreover, the surfactant concentration is found to contribute to the stability of the phase change nanoemulsion. Results indicate that the phase change nanoemulsion is a promising material for thermal storage applications.

  17. Excipient Nanoemulsions for Improving Oral Bioavailability of Bioactives

    PubMed Central

    Salvia-Trujillo, Laura; Martín-Belloso, Olga; McClements, David Julian

    2016-01-01

    The oral bioavailability of many hydrophobic bioactive compounds found in natural food products (such as vitamins and nutraceuticals in fruits and vegetables) is relatively low due to their low bioaccessibility, chemical instability, or poor absorption. Most previous research has therefore focused on the design of delivery systems to incorporate isolated bioactive compounds into food products. However, a more sustainable and cost-effect approach to enhancing the functionality of bioactive compounds is to leave them within their natural environment, but specifically design excipient foods that enhance their bioavailability. Excipient foods typically do not have functionality themselves but they have the capacity to enhance the functionality of nutrients present in natural foods by altering their bioaccessibility, absorption, and/or chemical transformation. In this review article we present the use of excipient nanoemulsions for increasing the bioavailability of bioactive components from fruits and vegetables. Nanoemulsions present several advantages over other food systems for this application, such as the ability to incorporate hydrophilic, amphiphilic, and lipophilic excipient ingredients, high physical stability, and rapid gastrointestinal digestibility. The design, fabrication, and application of nanoemulsions as excipient foods will therefore be described in this article. PMID:28344274

  18. Sustained release formulations of citronella oil nanoemulsion using cavitational techniques.

    PubMed

    Agrawal, Naveen; Maddikeri, Ganesh L; Pandit, Aniruddha B

    2017-05-01

    Nanoemulsion synthesis has proven to be an effective way for transportation of immobile, insoluble bioactive compounds. Citronella Oil (lemongrass oil), a natural plant extract, can be used as a mosquito repellent and has less harmful effects compared to its available market counterpart DEET (N, N-Diethyl-meta-toluamide). Nanoemulsion of citronella oil in water was prepared using cavitation-assisted techniques while investigating the effect of system parameters like HLB (Hydrophilic Lipophilic Balance), surfactant concentration, input energy density and mode of power input on emulsion quality. The present work also examines the effect of emulsification on release rate to understand the relationship between droplet size and the release rate. Minimum droplet size (60nm) of the emulsion was obtained at HLB of 14, S/O(1) ratio of 1.0, ultrasound amplitude of 50% and irradiation time of 5min. This study revealed that hydrodynamic cavitation-assisted emulsification is more energy efficient compared to ultrasonic emulsification. It was also found that the release rate of nanoemulsion enhanced as the droplet size of emulsion reduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Formulation and in vitro evaluation of ketoprofen in palm oil esters nanoemulsion for topical delivery.

    PubMed

    Sakeena, M H F; Muthanna, F A; Ghassan, Z A; Kanakal, M M; Elrashid, S M; Munavvar, A S; Azmin, M N

    2010-01-01

    The aim of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of ketoprofen. In this study, Palm Oil Esters (POEs) a newly introduced oil by Universiti Putra Malaysia researchers was chosen for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Oil-in-water nanoemulsion was prepared by spontaneous emulsification method. The droplets size was studied by laser scattering spectroscopy (Nanophox) and Transmission Electron Microscopy (TEM). Franz diffusion cells were used, to determine the drug release and drug transferred through methyl acetate cellulose membrane (artificial membrane). The results of droplets size analysis shows the droplets are in the range of nanoemulsion which is below than 500 nm. The in vitro release profile shows a sufficient percentage of drugs released through the methyl acetate cellulose membrane. This initial study showed that the nanoemulsion formulated using POEs has great potential for topical delivery of ketoprofen.

  20. Antioxidant activity and bioaccessibility of size-different nanoemulsions for lycopene-enriched tomato extract.

    PubMed

    Ha, Thi Van Anh; Kim, Saehoon; Choi, Yeri; Kwak, Hae-Soo; Lee, Sung Je; Wen, Jingyuan; Oey, Indrawati; Ko, Sanghoon

    2015-07-01

    Lycopene nanoemulsions were prepared to protect the antioxidant activity and improve the bioaccessibility of lycopene-enriched tomato extract (containing 6% of lycopene) by an emulsification-evaporation method. Lycopene nanoemulsions, with droplet sizes between 100 and 200 nm, exhibited higher anti-radical efficiency and antioxidant activity, than did those smaller than 100 nm. Strong protectability of lycopene in droplets smaller than 100 nm was associated with relatively slower rates of DPPH and ABTS reactions. In vitro bioaccessibility values of lycopene-enriched tomato extract, lycopene nanoemulsions with droplets larger than 100 nm (approximately 150 nm on average), and lycopene nanoemulsions with droplets smaller than 100 nm (69 nm on average) were 0.01, 0.53, and 0.77, respectively. Interestingly, nanoemulsions with droplets smaller than 100 nm showed the highest in vitro bioaccessibility, which could be interpreted as evidence of nanoemulsification enhancing the in vitro bioaccessibility of lycopene.

  1. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line.

    PubMed

    Ahmad, Mohammad; Sahabjada, -; Akhtar, Juber; Hussain, Arshad; Badaruddeen, -; Arshad, Md; Mishra, Anuradha

    2017-01-01

    Biological effects of rutin bioactive are limited due to its poor oral bioavailability and its degradation in aqueous environments. For the purpose of bioenhancement, different nanoemulsion systems of rutin were developed by aqueous titration method using water as dispersion media. The nanoemulsion systems were characterized for surface morphology, droplet size, polydispersity index, zeta potential, in vitro release profile and the formulations were optimized. The anticancer potential of optimized nanoemulsion was evaluated by cells viability (MTT) assay, nuclear condensation, and ROS activity using human prostate cancer (PC3) cell line. On the basis of cell viability data the inhibitory concentration (IC50) value for optimized nanoemulsion formulation on PC3 cancer cells was found to be 11.8 μM. Fluorescent microscopic analysis and intracellular ROS generation demonstrated significant ROS induction that might lead to triggering the apoptosis pathway. In conclusion, developed nanoemulsion displayed significant efficacy against prostate carcinoma cells.

  2. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line

    PubMed Central

    Ahmad, Mohammad; Sahabjada, -; Akhtar, Juber; Hussain, Arshad; Badaruddeen, -; Arshad, Md; Mishra, Anuradha

    2017-01-01

    Biological effects of rutin bioactive are limited due to its poor oral bioavailability and its degradation in aqueous environments. For the purpose of bioenhancement, different nanoemulsion systems of rutin were developed by aqueous titration method using water as dispersion media. The nanoemulsion systems were characterized for surface morphology, droplet size, polydispersity index, zeta potential, in vitro release profile and the formulations were optimized. The anticancer potential of optimized nanoemulsion was evaluated by cells viability (MTT) assay, nuclear condensation, and ROS activity using human prostate cancer (PC3) cell line. On the basis of cell viability data the inhibitory concentration (IC50) value for optimized nanoemulsion formulation on PC3 cancer cells was found to be 11.8 μM. Fluorescent microscopic analysis and intracellular ROS generation demonstrated significant ROS induction that might lead to triggering the apoptosis pathway. In conclusion, developed nanoemulsion displayed significant efficacy against prostate carcinoma cells. PMID:28694767

  3. Ultrasonic emulsification of food-grade nanoemulsion formulation and evaluation of its bactericidal activity.

    PubMed

    Ghosh, Vijayalakshmi; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2013-01-01

    Basil oil (Ocimum basilicum) nanoemulsion was formulated using non-ionic surfactant Tween80 and water by ultrasonic emulsification method. Process of nanoemulsion development was optimized for parameters such as surfactant concentration and emulsification time to achieve minimum droplet diameter with high physical stability. Surfactant concentration was found to have a negative correlation with droplet diameter, whereas emulsification time had a positive correlation with droplet diameter and also with intrinsic stability of the emulsion. Stable basil oil nanoemulsion with droplet diameter 29.3 nm was formulated by ultrasonic emulsification for 15 min. Formulated nanoemulsion was evaluated for antibacterial activity against Escherichia coli by kinetics of killing experiment. Fluorescence microscopy and FT-IR results showed that nanoemulsion treatment resulted alteration in permeability and surface features of bacterial cell membrane.

  4. Biodegradable polymer based encapsulation of neem oil nanoemulsion for controlled release of Aza-A.

    PubMed

    Jerobin, Jayakumar; Sureshkumar, R S; Anjali, C H; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2012-11-06

    Azadirachtin a biological compound found in neem have medicinal and pesticidal properties. The present work reports on the encapsulation of neem oil nanoemulsion using sodium alginate (Na-Alg) by cross linking with glutaraldehyde. Starch and polyethylene glycol (PEG) were used as coating agents for smooth surface of beads. The SEM images showed beads exhibited nearly spherical shape. Swelling of the polymeric beads reduced with coating which in turn decreased the rate of release of Aza-A. Starch coated encapsulation of neem oil nanoemulsion was found to be effective when compared to PEG coated encapsulation of neem oil nanoemulsion. The release rate of neem Aza-A from the beads into an aqueous environment was analyzed by UV-visible spectrophotometer (214 nm). The encapsulated neem oil nanoemulsion have the potential for controlled release of Aza-A. Neem oil nanoemulsion encapsulated beads coated with PEG was found to be toxic in lymphocyte cells.

  5. Transport of lipid nano-droplets through MDCK epithelial cell monolayer.

    PubMed

    Khatri, Pulkit; Shao, Jun

    2017-05-01

    This study aims to investigate the transport of lipid nano-droplets through MDCK epithelial cell monolayer. Nanoemulsions of self-nano-emulsifying drug delivery systems (SNEDDS) labeled with radioactive C18 triglyceride were developed. The effect of droplet size and lipid composition on the transport was investigated. The results showed that the lipid nano-droplet transport through MDCK cell monolayer was as high as 2.5%. The transport of lipid nano-droplets was higher for nanoemulsions of medium chain glycerides than the long chain glycerides. The transport was reduced by more than half when the average lipid nano-droplet size increased from 38nm to 261nm. The droplet size measurement verified the existence of lipid nano-droplets in the receiver chamber only when the nanoemulsions were added to the donor chamber but not when the surfactant or saline solution was added. Cryo-TEM images confirmed the presence of lipid nano-droplets in both donor and receiver chamber at the end of transport study. In conclusion, lipid nano-droplets can be transported through the cell monolayer. This finding may help to further explore the oral and other non-invasive delivery of macromolecules loaded inside SNEDDS.

  6. Pseudohypoparathyroidism presenting with bony deformities resembling rickets.

    PubMed

    Bajpai, Anurag; Sharma, Jyoti; Hari, Pankaj; Bagga, Arvind

    2004-04-01

    Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions.

  7. Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial activity

    PubMed Central

    Bei, Weiya; Zhou, Yan; Xing, Xuya; Zahi, Mohamed Reda; Li, Yuan; Yuan, Qipeng; Liang, Hao

    2015-01-01

    The aim of this study was to investigate a novel delivery system containing D-limonene and nisin by food organogel-nanoemulsion and study its effect on the antimicrobial activity. Organogel-nanoemulsion containing with D-limonene and nisin or without nisin was prepared by a homogenization method. Factors that may affect the droplet size and stability of organogel-nanoemulsion such as pressure and surfactant to oil ratio (SOR) were studied. The average droplet size decreased with pressure, and the organogel-nanoemulsion could achieve good stability at low SOR. Positive effects and outstanding antimicrobial activities of organogel-nanoemulsion containing with D-limonene and nisin were confirmed by minimal inhibitory concentrations comparison, growth curves of bacteria, scanning electron microscopy and determination of cell constituents’ release. Furthermore, the organogel-nanoemulsion applied as food preservative in milk also shown excellent antimicrobial performance. Overall, the research described in the current article show that organogel-nanoemulsion containing with D-limonene and nisin may be an effective antimicrobial system for the production and preservation of food. PMID:26441935

  8. Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability.

    PubMed

    Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli

    2011-12-14

    Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.

  9. Eugenol improves physical and chemical stabilities of nanoemulsions loaded with β-carotene.

    PubMed

    Guan, Yongguang; Wu, Jine; Zhong, Qixin

    2016-03-01

    Food-grade nanoemulsions are potential vehicles of labile lipophilic compounds such as β-carotene, but much work is needed to improve physical and chemical stabilities. The objective of this work was to study impacts of eugenol on physical and chemical stabilities of β-carotene-loaded nanoemulsions prepared with whey protein and lecithin. The combination of whey protein and lecithin resulted in stable nanoemulsions with eugenol added at 10% mass of soybean oil. Nanoemulsions, especially with eugenol, drastically reduced the degradation of β-carotene during ambient storage, heating at 60 and 80°C, and UV radiation at 254, 302, and 365nm. The droplet diameter of the nanoemulsion without eugenol increased from 153.6 to 227.3nm after 30-day ambient storage, contrasting with no significant changes of nanoemulsions with eugenol. Heating or UV radiation up to 8h did not significantly change the droplet diameter. Therefore, eugenol can be used to improve the stability of nanoemulsion delivery systems.

  10. Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial activity.

    PubMed

    Bei, Weiya; Zhou, Yan; Xing, Xuya; Zahi, Mohamed Reda; Li, Yuan; Yuan, Qipeng; Liang, Hao

    2015-01-01

    The aim of this study was to investigate a novel delivery system containing D-limonene and nisin by food organogel-nanoemulsion and study its effect on the antimicrobial activity. Organogel-nanoemulsion containing with D-limonene and nisin or without nisin was prepared by a homogenization method. Factors that may affect the droplet size and stability of organogel-nanoemulsion such as pressure and surfactant to oil ratio (SOR) were studied. The average droplet size decreased with pressure, and the organogel-nanoemulsion could achieve good stability at low SOR. Positive effects and outstanding antimicrobial activities of organogel-nanoemulsion containing with D-limonene and nisin were confirmed by minimal inhibitory concentrations comparison, growth curves of bacteria, scanning electron microscopy and determination of cell constituents' release. Furthermore, the organogel-nanoemulsion applied as food preservative in milk also shown excellent antimicrobial performance. Overall, the research described in the current article show that organogel-nanoemulsion containing with D-limonene and nisin may be an effective antimicrobial system for the production and preservation of food.

  11. Stability studies of silymarin nanoemulsion containing Tween 80 as a surfactant

    PubMed Central

    Parveen, Rabea; Baboota, Sanjula; Ali, Javed; Ahuja, Alka; Ahmad, Sayeed

    2015-01-01

    Background: Silymarin, a flavonolignan from “milk thistle” (Silybum marianum) plant is used almost exclusively for hepatoprotection. Because of its low bioavailability, it was incorporated into a nanoemulsion formulation. The aim of the present study was to check the stability of silymarin nanoemulsion at different temperatures for 3 months. Materials and Methods: The oil-in-water based nanoemulsion formulation was prepared by titration method. Silymarin nanoemulsion was characterized by droplet size, viscosity, and refractive index. Droplet size, viscosity, and refractive index were determined every month. The shelf-life of silymarin nanoemulsion was determined by accelerated stability testing. Results: It was found that there was no significant change in the droplet size, viscosity, and refractive index at refrigerator and room temperature during the period of 3 months. The half-life of the optimized nanoemulsion formulation was found to be 4.74 years at room temperature. Conclusion: These results indicated that stability of silymarin can be enhanced in nanoemulsion formulation using Tween 80 as a surfactant. PMID:26681893

  12. Quetiapine Nanoemulsion for Intranasal Drug Delivery: Evaluation of Brain-Targeting Efficiency.

    PubMed

    Boche, Mithila; Pokharkar, Varsha

    2017-04-01

    To evaluate the possibility of improved drug delivery of quetiapine fumarate (QTP), a nanoemulsion system was developed for intranasal delivery. Effects of different HLBs of Emalex LWIS 10, PEG 400 and Transcutol P, as co-surfactants, were studied on isotropic region of pseudoternary-phase diagrams of nanoemulsion system composed of capmul MCM (CPM) as oil phase, Tween 80 as surfactant and water. Phase behaviour, globule size, transmission electron microscope (TEM) photographs and brain-targeting efficiency of quetiapine nanoemulsion were investigated. In vitro dissolution study of optimised nanoemulsion formulation, with mean diameter 144 ± 0.5 nm, showed more than twofold increase in drug release as compared with pure drug. According to results of in vivo tissue distribution study in Wistar rats, intranasal administration of QTP-loaded nanoemulsion had shorter T max compared with that of intravenous administration. Higher drug transport efficiency (DTE%) and direct nose-to-brain drug transport (DTP%) was achieved by nanoemulsion. The nanoemulsion system may be a promising strategy for brain-targeted delivery of QTP.

  13. Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon Nanoemulsion Design

    PubMed Central

    Patel, Sravan K.; Williams, Jonathan; Janjic, Jelena M.

    2013-01-01

    This report describes novel perfluorocarbon (PFC) nanoemulsions designed to improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI). 19F MRI is a powerful non-invasive technique for monitoring cells of the immune system in vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The quality of 19F MRI is directly affected by the quality of ex vivo PFC cell labeling. When co-cultured with cells for longer periods of time, nanoemulsions tend to settle due to high specific weight of PFC oils (1.5–2.0 g/mL). This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are reported which demonstrate lack of sedimentation and high stability under cell labeling conditions. They are monodisperse, have small droplet size (~130 nm) and low polydispersity (<0.15), show a single peak in the 19F nuclear magnetic resonance spectrum at −71.4 ppm and possess high fluorine content. The droplet size and polydispersity remained unchanged after 160 days of follow up at three temperatures (4, 25 and 37 °C). Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented. PMID:25586263

  14. Evaluation of the antitumor effects of vitamin K2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate.

    PubMed

    Shi, Jia; Zhou, Songlei; Kang, Le; Ling, Hu; Chen, Jiepeng; Duan, Lili; Song, Yanzhi; Deng, Yihui

    2017-08-28

    Numerous studies have recently shown that vitamin K2 (VK2) has antitumor effects in a variety of tumor cells, but there are few reports demonstrating antitumor effects of VK2 in vivo. The antitumor effects of VK2 in nanoemulsions are currently not known. Therefore, we sought to characterize the antitumor potential of VK2 nanoemulsions in S180 tumor cells in the present study. Furthermore, a ligand conjugate sialic acid-cholesterol, with enhanced affinity towards the membrane receptors overexpressed in tumors, was anchored on the surface of the nanoemulsions to increase VK2 distribution to the tumor tissue. VK2 was encapsulated in oil-in-water nanoemulsions, and the physical and chemical stability of the nanoemulsions were characterized during storage at 25 °C. At 25 °C, all nanoemulsions remained physically and chemically stable with little change in particle size. An in vivo study using syngeneic mice with subcutaneously established S180 tumors demonstrated that intravenous or intragastric administration of VK2 nanoemulsions significantly suppressed the tumor growth. The VK2 nanoemulsions modified with sialic acid-cholesterol conjugate showed higher tumor growth suppression than the VK2 nanoemulsions, while neither of them exhibited signs of drug toxicity. In summary, VK2 exerted effective antitumor effects in vivo, and VK2 nanoemulsions modified with sialic acid-cholesterol conjugate enhanced the antitumor activity, suggesting that these VK2 may be promising agents for the prevention or treatment of tumor in patients.

  15. Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response.

    PubMed

    Ye, Jun; Dong, Wujun; Yang, Yanfang; Hao, Huazhen; Liao, Hengfeng; Wang, Bangyuan; Han, Xue; Jin, Yiqun; Xia, Xuejun; Liu, Yuling

    2017-06-01

    To overcome the drawbacks of high dose regimen and improve the outcomes of chemotherapy at a low dose, an immunotherapeutic nanoemulsion based combination of chemotherapeutic agent (paclitaxel) with immunomodulatory agent (vitamin E) was developed and evaluated for their antitumor effect against breast cancer. A total of five nanoemulsions loaded with various content of vitamin E were prepared and characterized. The immunoregulatory effects of vitamin E along with the overall antitumor efficacy of vitamin E-rich nanoemulsion with a low dose of paclitaxel were investigated through in vitro and in vivo experiments. Vitamin E-rich nanoemulsion exhibited relatively narrow size distribution, high entrapment efficiency and controlled in vitro release profile. In RAW264.7 cells, vitamin E-rich nanoemulsion significantly enhanced the secretion of Th1 cytokines and down-regulated the secretion of Th2 cytokine. In a co-culture system, vitamin E-rich nanoemulsion induced a high apoptosis rate in MDA-MB-231 cells as compared with vitamin E-low nanoemulsion. Furthermore, vitamin E-rich nanoemulsion exhibited superior in vivo antitumor efficacy in comparison with Taxol and vitamin E-low nanoemulsion at a paclitaxel dose of 4 mg/kg. Vitamin E-rich nanoemulsion has great potential for the treatment of breast cancers with a low dose of paclitaxel via driving Th1 immune response.

  16. Formation and stabilization of nanoemulsions using biosurfactants: Rhamnolipids.

    PubMed

    Bai, Long; McClements, David Julian

    2016-10-01

    Nanoemulsions are used in the food, cosmetics, personal care and pharmaceutical industries to provide desirable optical, textural, stability, and delivery characteristics. In many industrial applications, it is desirable to formulate nanoemulsions using natural ingredients so as to develop label-friendly products. Rhamnolipids are biosurfactants isolated from certain microorganisms using fermentation processes. They are glycolipids that have a polar head consisting of rhamnose units and a non-polar tail consisting of a hydrocarbon chain. In this study, the interfacial characteristics of this natural surfactant at medium chain triglyceride (MCT) oil-water interfaces were characterized, and its ability to form nanoemulsions was compared to that of another natural surfactant (quillaja saponins). The influence of rhamnolipid concentration, homogenization pressure, and oil type on the mean droplet diameter of emulsions produced by microfluidization was determined. Rhamnolipids were highly effective at forming small droplets (d32<0.15μm) at low surfactant-to-oil ratios (SOR<1:10) for MCT oil. Rhamnolipids could also be used to form small droplets using long chain triglyceride oils, such as corn and fish oil. Rhamnolipid-coated droplets were stable to aggregation over a range of pH values (5-9), salt concentrations (<100mM NaCl) and temperatures (20-90°C). However, droplet aggregation was observed at highly acidic (pH 2-4) and high ionic strength (200-500mM NaCl) conditions. These effects were attributed to a reduction in electrostatic repulsion at low pH and high salt levels. Rhamnolipid-coated droplets had a high negative charge at neutral pH that decreased in magnitude with decreasing pH. These results indicate that rhamnolipids are effective natural surfactants that may be able to replace synthetic surfactants in certain commercial applications.

  17. Pathogenecity of Pseudomonas aeruginosa in Oreochromis mossambicus and treatment using lime oil nanoemulsion.

    PubMed

    Thomas, John; Thanigaivel, S; Vijayakumar, S; Acharya, Kuntal; Shinge, Dhairyasheel; Seelan, T Samuel Jeba; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-04-01

    Fish diseases caused by Pseudomonas aeruginosa, a known pathogenic organism, is responsible for considerable economic losses in the commercial cultivation of Oreochromis mossambicus (Tilapia). The bacteria were injected into healthy fish through intramuscular injection, oral and immersion challenge. Infection was confirmed by histopathological investigation of the infected organs. Lime nanoemulsion was prepared and the effectiveness of the nanoemulsion was studied both in vitro and in vivo by well diffusion assay and in vivo in the artificially infected fish. Results showed that the lime nanoemulsion was effective against the P. aeruginosa infection in O. mossambicus both in vitro and in vivo.

  18. Edible lipid nanoparticles: digestion, absorption, and potential toxicity.

    PubMed

    McClements, David Julian

    2013-10-01

    Food-grade nanoemulsions are being increasingly used in the food and beverage industry to encapsulate, protect, and deliver hydrophobic functional components, such as oil-soluble flavors, colors, preservatives, vitamins, and nutraceuticals. These nanoemulsions contain lipid nanoparticles (radius <100 nm) whose physicochemical characteristics (e.g., composition, dimensions, structure, charge, and physical state) can be controlled by selection of appropriate ingredients and fabrication techniques. Nanoemulsions have a number of potential advantages over conventional emulsions for applications within the food industry: higher stability to particle aggregation and gravitational separation; higher optical transparency; and, increased bioavailability of encapsulated components. On the other hand, there are also some risks associated with consumption of lipid nanoparticles that should be considered before they are widely utilized, such as their ability to alter the fate of bioactive components within the gastrointestinal tract and the potential toxicity of some of the components used in their fabrication (e.g., surfactants and organic solvents). This article provides an overview of the current status of the biological fate and potential toxicity of food-grade lipid nanoparticles suitable for utilization within the food and beverage industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Interactions Between Antigens and Nanoemulsion Adjuvants: Separation and Characterization Techniques.

    PubMed

    Chan, Michelle Y; Fedor, Dawn M; Phan, Tony; V, Lucien Barnes; Kramer, Ryan M

    2017-01-01

    Determining the association of vaccine components in a formulation is of interest for designing and optimizing well characterized vaccines. Three methods are described to assess interactions between protein antigens and oil-in-water nanoemulsion adjuvants. The methods include (1) ultracentrifugation to measure free versus adjuvant-associated protein, (2) size exclusion chromatography (SEC) to qualitatively assess existing interactions, and (3) Native PAGE as a means to visualize the formulation run in its native state on a polyacrylamide gel. As with many techniques, the methods alone are not definitive, but data from multiple orthogonal assays can provide a more complete picture of protein-adjuvant interactions.

  20. Spinal Tuberculosis Resembling Neoplastic Lesions on MRI

    PubMed Central

    Kumar, Anil

    2015-01-01

    Background Tuberculous spondylitis is one of the commonest forms of skeletal tuberculosis in developing countries like India causing significant morbidity due to compression of spinal cord and adjacent nerve roots. Diagnosis and intervention at early stage can prevent permanent damage such as spinal deformity and neurological deficits. Aim The purpose of this study was to demonstrate atypical MRI features in cases of tubercular spondylitis resembling neoplastic lesions and to stress that tuberculous spondylitis should be one of the differential diagnoses in any spinal pathology especially in developing countries. Materials and Methods This was a prospective study done in the patients diagnosed as tuberculous spondylitis on 0.2 T Siemens MRI between June 2011 and December 2014 in a tertiary care hospital in India. Total 529 cases of tubercular spinal lesions were diagnosed. Out of which only 59 patients showed atypical features on MR imaging which resembled neoplastic lesions were included in the study. The diagnosis was confirmed by cytology, histopathology, serology and corroborative findings. Results Lumbo-sacral region involvement (30.5%) is the commonest in our study followed by dorsal and cervical region. Multiple level lesions are seen in 14 cases (23.7%). All the 59 (100%) cases show no involvement of intervetebral disc. Posterior appendage involvement seen in 32 cases (54.2%). Soft tissue component seen in Intraspinal (37.2%) and paraspinal (45.7%) compartments. Cord compression seen in 19 cases (32.2%), out which only 7 cases (11.8%) shows cord oedema. Conclusion On MRI, tubercular spondylitis may have variable pictures on imaging. For any spinal and paraspinal lesions, we should also consider the possibility of tubercular aetiology along with other. Since early diagnosis avoids unnecessary delay in the treatment thereby reducing morbidity and possible complications. PMID:26675162

  1. Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent : Nanoemulsion with Ursolic Acid Against T. cruzi.

    PubMed

    Vargas de Oliveira, Erika Cristina; Carneiro, Zumira Aparecida; de Albuquerque, Sérgio; Marchetti, Juliana Maldonado

    2017-02-21

    Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug's integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-D-galactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.

  2. Successfully improving ocular drug delivery using the cationic nanoemulsion, novasorb.

    PubMed

    Lallemand, Frederic; Daull, Philippe; Benita, Simon; Buggage, Ronald; Garrigue, Jean-Sebastien

    2012-01-01

    Topical ophthalmic delivery of active ingredients can be achieved using cationic nanoemulsions. In the last decade, Novagali Pharma has successfully developed and marketed Novasorb, an advanced pharmaceutical technology for the treatment of ophthalmic diseases. This paper describes the main steps in the development of cationic nanoemulsions from formulation to evaluation in clinical trials. A major challenge of the formulation work was the selection of a cationic agent with an acceptable safety profile that would ensure a sufficient ocular surface retention time. Then, toxicity and pharmacokinetic studies were performed showing that the cationic emulsions were safe and well tolerated. Even in the absence of an active ingredient, cationic emulsions were observed in preclinical studies to have an inherent benefit on the ocular surface. Moreover, clinical trials demonstrated the efficacy and safety of cationic emulsions loaded with cyclosporine A in patients with dry eye disease. Ongoing studies evaluating latanoprost emulsion in patients with ocular surface disease and glaucoma suggest that the beneficial effects on reducing ocular surface damage may also extend to this patient population. The culmination of these efforts has been the marketing of Cationorm, a preservative-free cationic emulsion indicated for the symptomatic treatment of dry eye.

  3. X-ray speckle measurements of concentrated nanoemulsions under shear

    NASA Astrophysics Data System (ADS)

    Abidib, Samy; Rogers, Michael; Leheny, Robert; Chen, Kui; Mason, Thomas; Harden, James

    We present in situ X-ray Photon Correlation Spectroscopy (XPCS) measurements of a set of concentrated nanoemulsions subjected to oscillatory shear. The nanoemulsion set contained samples with varying packing fractions of oil droplets (r 20nm) above the jamming transition. In order to study their elasticity, yielding, and flow at various shear amplitudes, we employed stroboscopic coherent X-ray scattering measurements triggered at the maximums of the shear cycle. The degree of correlation between speckle in images taken a full period apart is a direct measurement of particle rearrangements during cycling. A comparison of such XPCS ``echo'' measurements with rheological measurements shows an onset of irreversible particle motion at shear strains below the crossover of the storage and loss moduli, which is typically used to indicate the transition to viscoplastic flow. Moreover, the XPCS echo measurements indicate that particle irreversibility increases rapidly with shear amplitude, in contrast to the comparably smooth transition to yielding shown in bulk rheology measurements. However, the macroscopic yield strain observed in rheology and the microscopic yield strain identified from XPCS, which were strong functions of droplet packing fraction, tracked each other closely.

  4. Ultrasound assisted manufacturing of paraffin wax nanoemulsions: process optimization.

    PubMed

    Jadhav, A J; Holkar, C R; Karekar, S E; Pinjari, D V; Pandit, A B

    2015-03-01

    This work reports on the process optimization of ultrasound-assisted, paraffin wax in water nanoemulsions, stabilized by modified sodium dodecyl sulfate (SDS). This work focuses on the optimization of major emulsification process variables including sonication time, applied power and surfactant concentration. The effects of these variables were investigated on the basis of mean droplet diameter and stability of the prepared emulsion. It was found that the stable emulsion with droplet diameters about 160.9 nm could be formed with the surfactant concentration of 10 mg/ml and treated at 40% of applied power (power density: 0.61 W/ml) for 15 min. Scanning electron microscopy (SEM) was used to study the morphology of the emulsion droplets. The droplets were solid at room temperature, showing bright spots under polarized light and a spherical shape under SEM. The electrophoretic properties of emulsion droplets showed a negative zeta potential due to the adsorption of head sulfate groups of the SDS surfactant. For the sake of comparison, paraffin wax emulsion was prepared via emulsion inversion point method and was checked its intrinsic stability. Visually, it was found that the emulsion get separated/creamed within 30 min. while the emulsion prepared via ultrasonically is stable for more than 3 months. From this study, it was found that the ultrasound-assisted emulsification process could be successfully used for the preparation of stable paraffin wax nanoemulsions.

  5. Successfully Improving Ocular Drug Delivery Using the Cationic Nanoemulsion, Novasorb

    PubMed Central

    Lallemand, Frederic; Daull, Philippe; Benita, Simon; Buggage, Ronald; Garrigue, Jean-Sebastien

    2012-01-01

    Topical ophthalmic delivery of active ingredients can be achieved using cationic nanoemulsions. In the last decade, Novagali Pharma has successfully developed and marketed Novasorb, an advanced pharmaceutical technology for the treatment of ophthalmic diseases. This paper describes the main steps in the development of cationic nanoemulsions from formulation to evaluation in clinical trials. A major challenge of the formulation work was the selection of a cationic agent with an acceptable safety profile that would ensure a sufficient ocular surface retention time. Then, toxicity and pharmacokinetic studies were performed showing that the cationic emulsions were safe and well tolerated. Even in the absence of an active ingredient, cationic emulsions were observed in preclinical studies to have an inherent benefit on the ocular surface. Moreover, clinical trials demonstrated the efficacy and safety of cationic emulsions loaded with cyclosporine A in patients with dry eye disease. Ongoing studies evaluating latanoprost emulsion in patients with ocular surface disease and glaucoma suggest that the beneficial effects on reducing ocular surface damage may also extend to this patient population. The culmination of these efforts has been the marketing of Cationorm, a preservative-free cationic emulsion indicated for the symptomatic treatment of dry eye. PMID:22506123

  6. Modified Nanoemulsions with Iron Oxide for Magnetic Resonance Imaging

    PubMed Central

    Fan, Yongyi; Guo, Rui; Shi, Xiangyang; Allen, Steven; Cao, Zhengyi; Baker, James R.; Wang, Su He

    2016-01-01

    A nanoemulsion (NE) is a surfactant-based, oil-in-water, nanoscale, high-energy emulsion with a mean droplet diameter of 400–600 nm. When mixed with antigen and applied nasally, a NE acts as a mucosal adjuvant and induces mucosal immune responses. One possible mechanism for the adjuvant effect of this material is that it augments antigen uptake and distribution to lymphoid tissues, where the immune response is generated. Biocompatible iron oxide nanoparticles have been used as a unique imaging approach to study the dynamics of cells or molecular migration. To study the uptake of NEs and track them in vivo, iron oxide nanoparticles were synthesized and dispersed in soybean oil to make iron oxide-modified NEs. Our results show that iron oxide nanoparticles can be stabilized in the oil phase of the nanoemulsion at a concentration of 30 µg/μL and the iron oxide-modified NEs have a mean diameter of 521 nm. In vitro experiments demonstrated that iron oxide-modified NEs can affect uptake by TC-1 cells (a murine epithelial cell line) and reduce the intensity of magnetic resonance (MR) images by shortening the T2 time. Most importantly, in vivo studies demonstrated that iron oxide-modified NE could be detected in mouse nasal septum by both transmission electron microscopy and MR imaging. Altogether these experiments demonstrate that iron oxide-modified NE is a unique tool that can be used to study uptake and distribution of NEs after nasal application. PMID:28335351

  7. Formation of flavor oil microemulsions, nanoemulsions and emulsions: influence of composition and preparation method.

    PubMed

    Rao, Jiajia; McClements, David Julian

    2011-05-11

    This study aimed to establish conditions where stable microemulsions, nanoemulsions or emulsions could be fabricated from a nonionic surfactant (Tween 80) and flavor oil (lemon oil). Different colloidal dispersions could be formed by simple heat treatment (90 °C, 30 min) depending on the surfactant-to-oil ratio (SOR): emulsions (r > 100 nm) at SOR < 1; nanoemulsions (r < 100 nm) at 1 < SOR < 2; microemulsions (r < 10 nm) at SOR > 2. Turbidity, electrical conductivity, shear rheology, and DSC measurements suggested there was a kinetic energy barrier in the oil-water-surfactant systems at ambient temperature that prevented them from forming metastable emulsion/nanoemulsion or thermodynamically stable microemulsion systems. High energy homogenization (high pressure or ultrasonic homogenizer) or low energy homogenization (heating) could be used to form emulsions or nanoemulsions at low or intermediate SOR values; whereas only heating was necessary to form stable microemulsions at high SOR values.

  8. Design and evaluation of oral nanoemulsion drug delivery system of mebudipine.

    PubMed

    Khani, Samira; Keyhanfar, Fariborz; Amani, Amir

    2016-07-01

    A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8 ± 4.0 nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.

  9. Size controlled protein nanoemulsions for active targeting of folate receptor positive cells.

    PubMed

    Loureiro, Ana; Nogueira, Eugénia; Azoia, Nuno G; Sárria, Marisa P; Abreu, Ana S; Shimanovich, Ulyana; Rollett, Alexandra; Härmark, Johan; Hebert, Hans; Guebitz, Georg; Bernardes, Gonçalo J L; Preto, Ana; Gomes, Andreia C; Cavaco-Paulo, Artur

    2015-11-01

    Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size - the use of 5mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy.

  10. Chitosan microencapsulation of the dispersed phase of an O/W nanoemulsion to hydrochlorothiazide delivery.

    PubMed

    Mendes, Cassiana; Buttchevitz, Aline; Kruger, Jéssica Henriques; Caon, Thiago; Benedet, Patricia Oliveira; Lemos-Senna, Elenara Maria Teixeira; Silva, Marcos Antônio Segatto

    2017-09-10

    In view of biopharmaceutical limitations of hydrochlorothiazide (HCTZ), Trojan-type mucoadhesive systems were proposed, aiming to improve HCTZ pharmacological properties by modulating its release. Nanoemulsions were formed spontaneously by combining medium-chain triglycerides (Lipoid(®) S75 and Pluronic(®) F68) and high encapsulation efficiency was obtained. The mucoadhesive properties were provided by chitosan and microencapsulation of nanoemulsions in spray-dryer was successfully achieved by using Aerosil(®) as wall material. The rapid redispersion of nanoemulsion in simulated fluids led to a fast and complete release of HCTZ in gastric medium. The pharmacodynamics of HCTZ was improved, extending the diuretic activity. Once a simple and low-energy method contributed to obtain stable mucoadhesive nanoemulsions, advantages in terms of production could also be achieved, allowing easy scaling up. This novel mucoadhesive Trojan particulate system of HCTZ showed to be a promising approach to overcome limitations in terms of absorption and consequently improve the therapeutic efficacy.

  11. Influence of palmitoyl pentapeptide and Ceramide III B on the droplet size of nanoemulsion

    NASA Astrophysics Data System (ADS)

    Sondari, Dewi; Haryono, Agus; Harmami, Sri Budi; Randy, Ahmad

    2010-05-01

    The influence of the Palmitoyl Pentapeptide (PPp) and Ceramide IIIB (Cm III B) as active ingredients on the droplet size of nano-emulsion was studied using different kinds of oil (avocado oil, sweet almond oil, jojoba oil, mineral oil and squalene). The formation of nano-emulsions were prepared in water mixed non ionic surfactant/oils system using the spontaneous emulsification mechanism. The aqueous solution, which consist of water and Tween® 20 as a hydrophilic surfactant was mixed homogenously. The organic solution, which consist of oil and Span® 80 as a lipophilic surfactant was mixed homogenously in ethanol. Ethanol was used as a water miscible solvent, which can help the formation of nano-emulsion. The oil phase (containing the blend of surfactant Span® 80, ethanol, oil and active ingredient) and the aqueous phase (containing water and Tween® 20) were separately prepared at room temperatures. The oil phase was slowly added into aqueous phase under continuous mechanical agitation (18000 rpm). All samples were subsequently homogenized with Ultra-Turrax for 30 minutes. The characterizations of nano-emulsion were carried out using photo-microscope and particle size analyzer. Addition of active ingredients on the formation of nano-emulsion gave smallest droplet size compared without active ingredients addition on the formation of nano-emulsion. Squalene oil with Palmitoyl Pentapeptide (PPm) and Ceramide IIIB (Cm IIIB) gave smallest droplet size (184.0 nm) compared without Palmitoyl Pentapeptide and Ceramide IIIB (214.9 nm), however the droplets size of the emulsion prepared by the other oils still in the range of nano-emulsion (below 500 nm). The stability of nano-emulsion was observed using two methods. In one method, the stability of nano-emulsion was observed for three months at temperature of 5°C and 50°C, while in the other method, the stability nano-emulsion was observed by centrifuged at 12000 rpm for 30 minutes. Nanoemulsion with active ingredient

  12. Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene.

    PubMed

    Huang, Rwei-Fen S; Wei, Yi-Jun; Inbaraj, Baskaran Stephen; Chen, Bing-Huei

    2015-01-01

    Lycopene (LP), an important functional compound in tomatoes, and gold nanoparticles (AN), have received considerable attention as potential candidates for cancer therapy. However, the extreme instability and poor bioavailability of LP limits its in vivo application. This study intends to develop a nanoemulsion system incorporating both LP and AN, and to study the possible synergistic effects on the inhibition of the HT-29 colon cancer cell line. LP-nanogold nanoemulsion containing Tween 80 as an emulsifier was prepared, followed by characterization using transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, ultraviolet spectroscopy, and zeta potential analysis. The particle size as determined by TEM and DLS was 21.3±3.7 nm and 25.0±4.2 nm for nanoemulsion and 4.7±1.1 nm and 3.3±0.6 nm for AN, while the zeta potential of nanoemulsion and AN was -32.2±1.8 mV and -48.5±2.7 mV, respectively. Compared with the control treatment, both the combo (AN 10 ppm plus LP 12 μM) and nanoemulsion (AN 0.16 ppm plus LP 0.4 μM) treatments resulted in a five- and 15-fold rise in early apoptotic cells of HT-29, respectively. Also, the nanoemulsion significantly reduced the expressions of procaspases 8, 3, and 9, as well as PARP-1 and Bcl-2, while Bax expression was enhanced. A fivefold decline in the migration capability of HT-29 cells was observed for this nanoemulsion when compared to control, with the invasion-associated markers being significantly reversed through the upregulation of the epithelial marker E-cadherin and downregulation of Akt, nuclear factor kappa B, pro-matrix metalloproteinase (MMP)-2, and active MMP-9 expressions. The TEM images revealed that numerous nanoemulsion-filled vacuoles invaded cytosol and converged into the mitochondria, resulting in an abnormally elongated morphology with reduced cristae and matrix contents, demonstrating a possible passive targeting effect. The nanoemulsion containing vacuoles were engulfed and

  13. Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene

    PubMed Central

    Huang, Rwei-Fen S; Wei, Yi-Jun; Inbaraj, Baskaran Stephen; Chen, Bing-Huei

    2015-01-01

    Lycopene (LP), an important functional compound in tomatoes, and gold nanoparticles (AN), have received considerable attention as potential candidates for cancer therapy. However, the extreme instability and poor bioavailability of LP limits its in vivo application. This study intends to develop a nanoemulsion system incorporating both LP and AN, and to study the possible synergistic effects on the inhibition of the HT-29 colon cancer cell line. LP–nanogold nanoemulsion containing Tween 80 as an emulsifier was prepared, followed by characterization using transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, ultraviolet spectroscopy, and zeta potential analysis. The particle size as determined by TEM and DLS was 21.3±3.7 nm and 25.0±4.2 nm for nanoemulsion and 4.7±1.1 nm and 3.3±0.6 nm for AN, while the zeta potential of nanoemulsion and AN was −32.2±1.8 mV and −48.5±2.7 mV, respectively. Compared with the control treatment, both the combo (AN 10 ppm plus LP 12 μM) and nanoemulsion (AN 0.16 ppm plus LP 0.4 μM) treatments resulted in a five- and 15-fold rise in early apoptotic cells of HT-29, respectively. Also, the nanoemulsion significantly reduced the expressions of procaspases 8, 3, and 9, as well as PARP-1 and Bcl-2, while Bax expression was enhanced. A fivefold decline in the migration capability of HT-29 cells was observed for this nanoemulsion when compared to control, with the invasion-associated markers being significantly reversed through the upregulation of the epithelial marker E-cadherin and downregulation of Akt, nuclear factor kappa B, pro-matrix metalloproteinase (MMP)-2, and active MMP-9 expressions. The TEM images revealed that numerous nanoemulsion-filled vacuoles invaded cytosol and converged into the mitochondria, resulting in an abnormally elongated morphology with reduced cristae and matrix contents, demonstrating a possible passive targeting effect. The nanoemulsion containing vacuoles were engulfed

  14. Antimicrobial Activity of Nanoemulsion in Combination with Cetylpyridinium Chloride in Multidrug-Resistant Acinetobacter baumannii

    DTIC Science & Technology

    2013-08-01

    JR, Jr. 2010. Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury. Surgery 148:499 –509. 11. Ioannou CJ...effective antimicrobial activity against several A. baumannii strains evalu- ated at high dilutions and may be an ideal candidate for the topical treatment of...Reuter JD, Baker JR, Jr. 2001. A novel surfactant nanoemulsion with a unique non-irritant topical antimicrobial activity against bacteria, enveloped

  15. Improved Oral Bioavailability and Brain Transport of Saquinavir Upon Administration in Novel Nanoemulsion Formulations

    PubMed Central

    Vyas, Tushar K.; Shahiwala, Aliasgar; Amiji, Mansoor M.

    2008-01-01

    The aim of this investigation was to develop novel oil-in-water (o/w) nanoemulsions containing saquinavir (SQV), an anti-HIV protease inhibitor, for enhanced oral bioavailability and brain disposition. SQV was dissolved in different types of edible oils rich in essential polyunsaturated fatty acids (PUFA) to constitute the internal oil phase of the nanoemulsions. The external phase consisted of surfactants Lipoid®-80 and deoxycholic acid dissolved in water. The nanoemulsions with an average oil droplet size of 100-200 nm, containing tritiated [3H]-SQV, were administered orally and intravenously to male Balb/c mice. The SQV bioavailability as well as distribution in different organ systems was examined. SQV concentrations in the systemic circulation administered in flax-seed oil nanoemulsions were 3-fold higher as compared to the control aqueous suspension. The oral bioavailability and distribution to the brain, a potential sanctuary site for HIV, were significantly enhanced with SQV delivered in nanoemulsion formulations. In comparing SQV in flax-seed oil nanoemulsion with aqueous suspension, the maximum concentration (Cmax) and the area-under-the-curve (AUC) values were found to be 5-fold and 3-fold higher in the brain, respectively, suggesting enhanced rate and extent of SQV absorption following oral administration of nanoemulsions. The results of this study show that oil-in-water nanoemulsions made with PUFA-rich oils may be very promising for HIV/AIDS therapy, in particular, for reducing the viral load in important anatomical reservoir sites. PMID:17651927

  16. Body elimination attitude family resemblance in Kuwait.

    PubMed

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in.

  17. Giant sublingual epidermoid cyst resembling plunging ranula

    PubMed Central

    Verma, Sandeep; Kushwaha, Jitendra Kumar; Sonkar, A A; Kumar, Rahul; Gupta, Rajni

    2012-01-01

    Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. We describe a rare case of large epidermoid cyst in floor of mouth, with an oral as well as submental component resembling plunging ranula reported in the literature from India. We present a case of a 16-year-old girl with complaints of a mass in sublingual region, difficulty chewing, and dysphagia for about 5 months. Fine-needle aspiration cytology showed keratin flakes and proteinaceous material. Contrast-enhanced CT oral cavity was done and showed 7.0 × 5 × 4.5 cm well-circumscribed non-enhancing cystic mass extending into the floor of the mouth. On examination, a firm swelling was noticed in the submental area, extending down to the thyroid notch. The patient underwent surgical removal of the mass. On histopathology, acidophilic stratum corneum and basophilic dot like staining of stratum granulosum, which is the hallmark of an epidermoid cyst, were seen. PMID:23833501

  18. Enhanced removal from the plasma of LDL-like nanoemulsion cholesteryl ester in trained men compared with sedentary healthy men.

    PubMed

    Vinagre, Carmen G C; Ficker, Elisabeth S; Finazzo, Claudia; Alves, Maria J N; de Angelis, Katia; Irigoyen, Maria Claudia; Negrão, Carlos E; Maranhão, Raul C

    2007-10-01

    The objective of this study was to evaluate the effects of exercise training on plasma removal of a cholesterol-rich nanoemulsion (LDE) that mimics low-density lipoprotein (LDL) lipid structure and binds to LDL receptors. LDE-derived cholesteryl ester plasma kinetics was studied in 24 exercise-trained and 20 sedentary male subjects. LDE labeled with [(14)C]cholesteryl ester was injected intravenously, and plasma samples were collected over a 24-h period to determine radioisotope decay curves. LDL cholesterol concentration was similar in both groups. Fractional clearance rate (FCR) of the nanoemulsion label was greater in the exercise-trained group compared with the sedentary group (0.138 +/- 0.152 and 0.0261 +/- 0.023 h(-1), respectively). A positive correlation was found (r = 0.60, P < 0.01) between FCR and peak O(2) consumption in trained subjects. Circulating oxidized LDL levels were lower in trained subjects compared with the sedentary group (9.0 +/- 2.0 and 16.0 +/- 3.0 mU/l). LDE was also injected into control and LDL receptor gene knockout mice submitted and not submitted to training. Muscle LDE uptake percentage was increased in the trained mice compared with the untrained mice (1.1 +/- 0.8 and 0.2 +/- 0.1, respectively, P < 0.0001) in the control group but not in the knockout animals, indicating that the LDL receptor is involved in the increased uptake elicited by exercise. These results show that exercise training increases LDE plasma removal, which in turn suggests that it also increases LDL receptors or LDL receptor activity.

  19. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation.

    PubMed

    Đorđević, Sanela M; Cekić, Nebojša D; Savić, Miroslav M; Isailović, Tanja M; Ranđelović, Danijela V; Marković, Bojan D; Savić, Saša R; Timić Stamenić, Tamara; Daniels, Rolf; Savić, Snežana D

    2015-09-30

    This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution <0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats

    PubMed Central

    Li, Xiaoyang; Qi, Jianping; Xie, Yunchang; Zhang, Xi; Hu, Shunwen; Xu, Ying; Lu, Yi; Wu, Wei

    2013-01-01

    This study aimed to prepare nanoemulsions coated with alginate/chitosan for oral insulin delivery. Uncoated nanoemulsions were prepared by homogenization of a water in oil in water (w/o/w) multiple emulsion that was composed of Labrafac® CC, phospholipid, Span™ 80 and Cremorphor® EL. Coating of the nanoemulsions was achieved based on polyelectrolyte cross-linking, with sequential addition of calcium chloride and chitosan to the bulk nanoemulsion dispersion that contained alginate. The particle size of the coated nanoemulsions was about 488 nm and the insulin entrapment ratio was 47.3%. Circular dichroism spectroscopy proved conformational stability of insulin against the preparative stress. In vitro leakage study indicated well-preserved integrity of the nanoemulsions in simulated gastric juices. Hypoglycemic effects were observed in both normal and diabetic rats. The relative pharmacological bioavailability of the coated nanoemulsion with 25 and 50 IU/kg insulin were 8.42% and 5.72% in normal rats and 8.19% and 7.84% in diabetic rats, respectively. Moreover, there were significantly prolonged hypoglycemic effects after oral administration of the coated nanoemulsions compared with subcutaneous (sc) insulin. In conclusion, the nanoemulsion coated with alginate/chitosan was a potential delivery system for oral delivery of polypeptides and proteins. PMID:23293517

  1. Improvement of colchicine oral bioavailability by incorporating eugenol in the nanoemulsion as an oil excipient and enhancer.

    PubMed

    Shen, Qi; Wang, Ying; Zhang, Yi

    2011-01-01

    The effect of eugenol on colchicine transport across an isolated rat intestinal membrane was studied using an in vitro diffusion chamber system. We found that eugenol increased the absorptive transport of the drug efficiently. The effect of eugenol on intestinal absorption of colchicine in an oral administrative nanoemulsion formulation was also demonstrated in vivo. The colchicine nanoemulsion was prepared with isopropyl myristate, eugenol, Tween80, ethanol and water, and eugenol was used as an oil phase in the formulation; an average particle size of this nanoemulsion was 41.2 ± 7.2 nm. The permeation of colchicine in the nanoemulsion across the intestinal membrane was significantly different from that of the control group (0.2 mM colchicine). Finally, co-administration of eugenol in colchicine nanoemulsion to enhance the colchicine bioavailability was investigated by an oral administration method. After oral administration of colchicine (8 mg/kg) in the form of either the nanoemulsion or in free colchicine solution, the relative bioavailability of nanoemulsion and eugenol-nanoemulsion were enhanced by about 1.6- and 2.1-fold, respectively, compared with free colchicine solution. The procedure indicated that the intestinal absorption of colchicine was enhanced significantly by eugenol in the tested nanoemulsion. All the results suggested that eugenol is an efficient component in an oral administrative formulation for improving the intestinal absorption of colchicine.

  2. Identification of an emulsifier and conditions for preparing stable nanoemulsions containing the antioxidant astaxanthin.

    PubMed

    Kim, D-M; Hyun, S-S; Yun, P; Lee, C-H; Byun, S-Y

    2012-02-01

    In this study, oil-in-water nanoemulsions of astaxanthin were prepared by high-pressure homogenization. The influence of emulsifying conditions including emulsifier type, concentration, passing time, astaxanthin concentration and coantioxidants were optimized. The stabilities of nanoemulsions were measured using zetasizer, FF-SEM, TEM, colorimeter and particle size analyzer. The mean diameter of the dispersed particles containing astaxanthin ranged from 160 to 190 nm. The size distribution was unimodal and extended from 100 to 200 nm. The nanoemulsions prepared with glyceryl citrate/lactate/linoleate/oleate (glyceryl ester) had smaller particle size and narrower size distribution than the emulsion prepared with hydrogenated lecithin. Stable incorporation of astaxanthin in nanoemulsion was performed and checked using HPLC, FF-SEM and TEM. The nanoemulsion was not significantly affected during storage under light and thermal condition for one month indicating that the nanoemulsion had a zeta potential of less than -41 mV, indicating a stable colloid. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  3. Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system.

    PubMed

    Esmaeili, Fariba; Rajabnejhad, Saeid; Partoazar, Ali Reza; Mehr, Shahram Ejtemaei; Faridi-Majidi, Reza; Sahebgharani, Mousa; Syedmoradi, Leila; Rajabnejhad, Mohammad Reza; Amani, Amir

    2016-11-01

    Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam.

  4. Experimental design in formulation of diazepam nanoemulsions: physicochemical and pharmacokinetic performances.

    PubMed

    Đorđević, Sanela M; Radulović, Tamara S; Cekić, Nebojša D; Ranđelović, Danijela V; Savić, Miroslav M; Krajišnik, Danina R; Milić, Jela R; Savić, Snežana D

    2013-11-01

    With the aid of experimental design, we developed and characterized nanoemulsions for parenteral drug delivery. Formulations containing a mixture of medium-chain triglycerides and soybean oil as oil phase, lecithin (soybean/egg) and polysorbate 80 as emulsifiers, and 0.1 M phosphate buffer solution (pH 8) as aqueous phase were prepared by cold high-pressure homogenization. To study the effects of the oil content, lecithin type, and the presence of diazepam as a model drug and their interactions on physicochemical characteristics of nanoemulsions, a three factor two-level full factorial design was applied. The nanoemulsions were evaluated concerning droplet size and size distribution, surface charge, viscosity, morphology, drug-excipient interactions, and physical stability. The characterization revealed the small spherical droplets in the range 195 -220 nm with polydispersity index below 0.15 and zeta potential between -30 and - 60 mV. Interactions among the investigated factors, rather than factors alone, were shown to more profoundly affect nanoemulsion characteristics. In vivo pharmacokinetic study of selected diazepam nanoemulsions with different oil content (20%, 30%, and 40%, w/w) demonstrated fast and intense initial distribution into rat brain of diazepam from nanoemulsions with 20% and 30% (w/w) oil content, suggesting their applicability in urgent situations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. EGFR Targeted Theranostic Nanoemulsion For Image-Guided Ovarian Cancer Therapy

    PubMed Central

    Ganta, Srinivas; Singh, Amit; Kulkarni, Praveen; Keeler, Amanda W.; Piroyan, Aleksandr; Sawant, Rupa R.; Patel, Niravkumar R.; Davis, Barbara; Ferris, Craig; O’Neal, Sara; Zamboni, William; Amiji, Mansoor M.; Coleman, Timothy P.

    2015-01-01

    Purpose Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. Methods The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. Results Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. Conclusions Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression. PMID:25732960

  6. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions.

    PubMed

    Yu, Hailong; Huang, Qingrong

    2012-05-30

    Curcumin is a natural bioactive compound with many health-promoting benefits. Its low oral bioavailability limits its application in functional foods. In the present study, novel organogel-based nanoemulsions have been developed for oral delivery of curcumin and improvement of its bioavailability. Recently developed curcumin organogel was used as the oil phase in the curcumin nanoemulsion formulation. Tween 20 was selected as the emulsifier on the basis of maximum in vitro bioaccessibility of curcumin in the nanoemulsion. In vitro lipolysis profile revealed that the digestion of nanoemulsion was significantly faster and more complete than the organogel. Permeation experiments on Caco-2 cell monolayers suggested that digestion-diffusion was the major absorption mechanism for curcumin in the nanoemulsion. Furthermore, in vivo pharmacokinetics analysis on mice confirmed that the oral bioavailability of curcumin in the nanoemulsion was increased by 9-fold compared with unformulated curcumin. This novel formulation approach may also be used for oral delivery of other poorly soluble nutraceuticals with high loading capacity, which has significant impact in functional foods, dietary supplements and pharmaceutical industries.

  7. Physiochemical and cytotoxicity study of TPGS stabilized nanoemulsion designed by ultrasonication method.

    PubMed

    Kaur, Khushwinder; Kumar, Raj; Arpita; Goel, Sumit; Uppal, Shivani; Bhatia, Alka; Mehta, S K

    2017-01-01

    The main aim of the present work was to prepare TPGS stabilized D-α-Tocopherol, lemon oil, tween-80, and water nanoemulsion by low cost and highly effective sonication method. The prepared nanoemulsion showed good stability for 60days at variable temperature conditions i.e. 4, 25 and 37°C. The tolerance of the prepared nanoemulsion to salt (50mM-500mM) and pH (pH 2-pH 7.4) was also studied. The morphology and droplet size of pure and quinine loaded nanoemulsion was characterized with transmission electron microscopy. The prepared formulation was transparent and the obtained average particle size ranged between 25nm and 35nm. The nanoemulsion was found to be non toxic. The cell viability study of pure nanoemulsion carried out on Hep G2 cells revealed that the cell viability was 100%. The formulation further exhibited high quinine loading and release capacity with cumulative release up to 76±2% and 65±2% at pH 7.4 and pH 5.5 respectively. The interaction between quinine and vitamins (riboflavin, thiamine and biotin) was also carried out (aqueous medium). The study revealed that riboflavin had strong interaction with quinine and vitamins vis-à-vis thiamine and biotin.

  8. Vitamin E-enriched nanoemulsions formed by emulsion phase inversion: factors influencing droplet size and stability.

    PubMed

    Mayer, Sinja; Weiss, Jochen; McClements, David Julian

    2013-07-15

    There is considerable interest in using nanoemulsions as delivery systems for lipophilic bioactive ingredients, such as oil-soluble vitamins. Nanoemulsions can be fabricated using either high-energy or low-energy methods, but the latter offer advantages in terms of low cost, higher energy efficiency, and simplicity of implementation. In this study, the emulsion phase inversion (EPI) method was used to produce food-grade nanoemulsions enriched with vitamin E acetate. The EPI method simply involves titrating water into a mixture containing oil and surfactant, which initially leads to the formation of a water-in-oil emulsion that then inverts into an oil-in-water emulsion. Oil composition, surfactant type, and surfactant-to-oil ratio (SOR) were all found to influence the particle size distribution of the systems produced. Nanoemulsions with a mean particle diameter of 40 nm could be produced at a final system composition of 2 wt% MCT, 8 wt%vitamin E acetate, and 20 wt% Tween 80. The EPI method was shown to be unsuitable for producing nanoemulsions from label-friendly surfactants, such as Quillaja saponin, whey protein, casein, and sucrose monoesters. The EPI method was more effective at producing nanoemulsions at high SOR than microfluidization, but much less effective at low SOR. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Mucoadhesive nanoemulsion-based intranasal drug delivery system of olanzapine for brain targeting.

    PubMed

    Kumar, Mukesh; Misra, Ambikanandan; Mishra, A K; Mishra, Pushpa; Pathak, Kamla

    2008-12-01

    The objective of the present study was to optimize olanzapine nanoemulsion (ONE), for nose-to-brain delivery. The nanoemulsions and olanzapine mucoadhesive nanoemulsions (OMNEs) were prepared using water titration method and characterized for technical and electrokinetic properties. Biodistribution of nanoemulsions and olanzapine solution (OS) in the brain and blood of rats following intranasal (intranasal) and intravenous (intravenous) administrations were examined using optimized technetium-labeled ((99m)Tc-labeled) olanzapine formulations. The brain/blood uptake ratios of 0.45, 0.88, 0.80, and 0.04 of OS (intranasal), ONE (intranasal), OMNE (intranasal), ONE (intravenous), respectively, at 0.5 h are indicative of direct nose-to-brain transport (DTP). Higher % drug targeting efficiency (%DTE) and %DTP for mucoadhesive nanoemulsions indicated effective brain targeting of olanzapine among the prepared nanoemulsions. Gamma scintigraphy imaging of the rat brain conclusively demonstrated rapid and larger extent of transport of olanzapine by OMNE (intranasal), when compared with OS (intranasal), ONE (intranasal), and ONE (intravenous), into the rat brain.

  10. Development of EGFR Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer

    PubMed Central

    Ganta, Srinivas; Singh, Amit; Patel, Niravkumar R.; Cacaccio, Joseph; Rawal, Yashesh H.; Davis, Barbara J.; Amiji, Mansoor M.; Coleman, Timothy P.

    2014-01-01

    Purpose Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations. Methods The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP. Results The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®. Conclusion The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer. PMID:24643932

  11. Characterization of basil seed gum-based edible films incorporated with Zataria multiflora essential oil nanoemulsion.

    PubMed

    Hashemi Gahruie, Hadi; Ziaee, Esmaeil; Eskandari, Mohammad Hadi; Hosseini, Seyed Mohammad Hashem

    2017-06-15

    Direct introduction of essential oils (EOs) into biopolymer-based packaging materials faces various challenges such as insolubility and loss of activity. The aim of this study was increasing the bioactivity of Zataria multiflora essential oil (ZMEO) through first making a nanoemulsion and then immobilizing within basil seed gum (BSG)-based film network. ZMEO (nano)emulsions were prepared using high intensity ultrasound approach at 150W and various sonication times (0, 2.5, 5 and 10min). An increase in the antibacterial activity of ZMEO nanoemulsion was observed by decreasing the nanoemulsion droplet size. Increasing nanoemulsion concentration in BSG film matrix improved the mechanical properties. Scanning electron micrographs showed that the presence of ZMEO nanoemulsions resulted in significant changes in the microstructure of BSG films. Antimicrobial films were effective against potential foodborne pathogens. This innovative incorporation of EOs into biopolymer-based films may have implications in extending the shelf life of food products through retarding the release of volatile constituents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide.

    PubMed

    Morsi, Nadia; Ibrahim, Magdy; Refai, Hanan; El Sorogy, Heba

    2017-06-15

    In the present work the antiglaucoma drug, acetazolamide, was formulated as an ion induced nanoemulsion-based in situ gel for ocular delivery aiming a sustained drug release and an improved therapeutic efficacy. Different acetazolamide loaded nanoemulsion formulations were prepared using peanut oil, tween 80 and/or cremophor EL as surfactant in addition to transcutol P or propylene glycol as cosurfactant. Based on physicochemical characterization, the nanoemulsion formulation containing mixed surfactants and transcutol P was selected to be incorporated into ion induced in situ gelling systems composed of gellan gum alone and in combination with xanthan gum, HPMC or carbopol. The nanoemulsion based in situ gels showed a significantly sustained drug release in comparison to the nanoemulsion. Gellan/xanthan and gellan/HPMC possessed good stability at all studied temperatures, but gellan/carbopol showed partial drug precipitation upon storage and was therefore excluded from the study. Gellan/xanthan and gellan/HPMC showed higher therapeutic efficacy and more prolonged intraocular pressure lowering effect relative to that of commercial eye drops and oral tablet. Gellan/xanthan showed superiority over gellan/HPMC in all studied parameters and is thus considered as a promising mucoadhesive nanoemulsion-based ion induced in situ gelling formula for topical administration of acetazolamide. Copyright © 2017. Published by Elsevier B.V.

  13. A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone.

    PubMed

    Hu, Zhenhua; Liao, Meiling; Chen, Yinghui; Cai, Yunpeng; Meng, Lele; Liu, Yajun; Lv, Nan; Liu, Zhenguo; Yuan, Weien

    2012-01-01

    Silicone oil, as a major component in conditioner, is beneficial in the moisture preservation and lubrication of hair. However, it is difficult for silicone oil to directly absorb on the hair surface because of its hydrophobicity. Stable nanoemulsions containing silicone oil may present as a potential solution to this problem. Silicone oil nanoemulsions were prepared using the oil-in-water method with nonionic surfactants. Emulsion particle size and distribution were characterized by scanning electron microscopy. The kinetic stability of this nanoemulsion system was investigated under accelerated stability tests and long-term storage. The effect of silicone oil deposition on hair was examined by analyzing the element of hair after treatment of silicone oil nanoemulsions. Nonionic surfactants such as Span 80 and Tween 80 are suitable emulsifiers to prepare oil-in-water nanoemulsions that are both thermodynamically stable and can enhance the absorption of silicone oil on hair surface. The silicone oil-in-water nanoemulsions containing nonionic surfactants present as a promising solution to improve the silicone oil deposition on the hair surface for hair care applications.

  14. A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

    PubMed Central

    Hu, Zhenhua; Liao, Meiling; Chen, Yinghui; Cai, Yunpeng; Meng, Lele; Liu, Yajun; Lv, Nan; Liu, Zhenguo; Yuan, Weien

    2012-01-01

    Background Silicone oil, as a major component in conditioner, is beneficial in the moisture preservation and lubrication of hair. However, it is difficult for silicone oil to directly absorb on the hair surface because of its hydrophobicity. Stable nanoemulsions containing silicone oil may present as a potential solution to this problem. Methods Silicone oil nanoemulsions were prepared using the oil-in-water method with nonionic surfactants. Emulsion particle size and distribution were characterized by scanning electron microscopy. The kinetic stability of this nanoemulsion system was investigated under accelerated stability tests and long-term storage. The effect of silicone oil deposition on hair was examined by analyzing the element of hair after treatment of silicone oil nanoemulsions. Results Nonionic surfactants such as Span 80 and Tween 80 are suitable emulsifiers to prepare oil-in-water nanoemulsions that are both thermodynamically stable and can enhance the absorption of silicone oil on hair surface. Conclusion The silicone oil-in-water nanoemulsions containing nonionic surfactants present as a promising solution to improve the silicone oil deposition on the hair surface for hair care applications. PMID:23166436

  15. Multiplexed detection of various breast cancer cells by perfluorocarbon/quantum dot nanoemulsions conjugated with antibodies

    NASA Astrophysics Data System (ADS)

    Bae, Pan Kee; Chung, Bong Hyun

    2014-07-01

    The effective targeting of cancer cell surface antigens is an attractive approach in cancer diagnosis and therapy. Multifunctional nanoprobes with cell-targeting specificity are likely to find important applications in bioanalysis, biomedicine, and clinical diagnosis. In this study, we have fabricated biocompatible perfluorocan/quantum dot nanoemulsions as bimodal imaging nanoprobes for the targeting of breast cancer cells. Perfluorocarbon/quantum dot nanoemulsions conjugated with monoclonal antibodies, as a type of bimodal imaging nanoprobe based on 19 F-MR and optical imaging, have been synthesized and applied for targeted imaging of three different breast cancer cells (SKBR3, MCF-7, MDA-MB 468), respectively. We have shown that the cancer-detection capabilities of antibody-conjugated PFC/QDs nanoemulsions could be successfully applied to target of various breast cancer cells. These modified PFC/QDs nanoemulsions were shown to target the cancer cell surface receptors specially. Conjugation of ligands to nanoemulsions targeting over-expressed cell surface receptors is a promising approach for targeted imaging to tumor cells. We further propose that the PFC/QDs nanoemulsions could be used in targeted imaging of breast cancer cells.

  16. Compared with Powdered Lutein, a Lutein Nanoemulsion Increases Plasma and Liver Lutein, Protects against Hepatic Steatosis, and Affects Lipoprotein Metabolism in Guinea Pigs.

    PubMed

    Murillo, Ana Gabriela; Aguilar, David; Norris, Gregory H; DiMarco, Diana M; Missimer, Amanda; Hu, Siqi; Smyth, Joan A; Gannon, Sarah; Blesso, Christopher N; Luo, Yangchao; Fernandez, Maria Luz

    2016-10-01

    It is not clear how oil-in-water nanoemulsions of lutein may affect bioavailability and consequently alter lipoprotein metabolism, oxidative stress, and inflammation. The bioavailability as well as effects of a powdered lutein (PL) and an oil-in-water lutein nanoemulsion (NANO; particle size: 254.2 nm; polydispersity index: 0.29; and ζ-potential: -65 mV) on metabolic variables in liver, plasma, and adipose tissue in a guinea pig model of hepatic steatosis were evaluated. Twenty-four 2-mo-old male Hartley guinea pigs, weighing 200-300 g (n = 8/group), were fed diets containing 0.25 g cholesterol/100 g to induce liver injury for the duration of the study. They were allocated to control (0 mg lutein), PL (3.5 mg/d), or NANO (3.5 mg/d) groups. After 6 wk, plasma, liver, and adipose tissue were collected for determination of lutein, plasma lipids, tissue cholesterol, and inflammatory cytokines. The NANO group had 2-fold higher concentrations of lutein in plasma (P < 0.001) and 1.6-fold higher concentrations in liver (P < 0.001) than did the PL group, indicating greater bioavailability of this carotenoid. The NANO group also had 24% lower hepatic steatosis scores (P < 0.05), 31% lower hepatic cholesterol accumulation (P < 0.05), and 64% lower plasma alanine aminotransferase (P < 0.05) than did the control group. Hepatic oxidized LDL was 55% lower in both the PL and NANO groups than in the control group (P < 0.05). In plasma, the NANO group had 2-fold higher concentrations of LDL and HDL cholesterol as well as a 2-fold higher number of VLDL, LDL, and HDL particles than did the other 2 groups as evaluated by nuclear magnetic resonance. Furthermore, the NANO group had 15% higher concentrations of free cholesterol in adipose tissue, resulting in higher concentrations of inflammatory markers, than did the other 2 groups. These results indicate that, although this lutein nanoemulsion exerted protective effects against hepatic steatosis, plasma lipoproteins and adipose tissue

  17. Development of Food-Grade Curcumin Nanoemulsion and its Potential Application to Food Beverage System: Antioxidant Property and In Vitro Digestion.

    PubMed

    Joung, Hee Joung; Choi, Mi-Jung; Kim, Jun Tae; Park, Seok Hoon; Park, Hyun Jin; Shin, Gye Hwa

    2016-03-01

    Curcumin nanoemulsions (Cur-NEs) were developed with various surfactant concentrations by using high pressure homogenization and finally applied to the commercial milk system. Characterization of Cur-NEs was performed by measuring the droplet size and polydispersity index value at different Tween 20 concentrations. The morphology of the Cur-NEs was observed by confocal laser scanning microscopy and transmission electron microscopy. Antioxidant activity and in vitro digestion ability were tested using 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, pH-stat method, and thiobarbituric acid reactive substances assays. Cur-NEs were found to be physically stable for 1 mo at room temperature. The surfactant concentration affects particle formation and droplet size. The mean droplet size decreased from 122 to 90 nm when surfactant concentration increased 3 times. Cur-NEs had shown an effective oxygen scavenging activity. Cur-NEs-fortified milk showed significantly lower lipid oxidation than control (unfortified) milk and milk containing curcumin-free nanoemulsions. These properties make Cur-NEs suitable systems for the beverage industry.

  18. Non-enzymatic glucose detection using magnetic nanoemulsions

    SciTech Connect

    Mahendran, V.; Philip, John

    2014-09-22

    We probe the optical properties and intermolecular interactions in magnetically responsive nanoemulsions in the presence of glucose. The equilibrium interdroplet distance between the emulsion droplets in an one-dimensional array increases by several nanometers in the presence of glucose because of intermolecular hydrogen bonding with sodium dodecyl sulphate molecules at the oil-water interface that gives rise to stretched lamellae-like structure. The observed large red shift in the diffracted Bragg peak (∼50–100 nm) and the linear response in the glucose concentration range of 0.25–25 mM offer a simple, fast, and cost effective non-enzymatic approach for glucose detection.

  19. Encapsulation of natural ingredient for skin protection via nanoemulsion process

    NASA Astrophysics Data System (ADS)

    Asmatulu, Eylem; Usta, Aybala; Alzahrani, Naif; Patil, Vinay; Vanderwall, Adeesha

    2017-04-01

    Many of the sunscreens are used during the hot summer time to protect the skin surface. However, some of ingredients in the sunscreens, such as oxybenzone, retinyl palmitate and synthetic fragrances including parabens, phthalates and synthetic musk may disrupt the cells on the skin and create harmful effects to human body. Natural oils may be considered for substitution of harmful ingredients in sunscreens. Many natural oils (e.g., macadamia oil, sesame oil, almond oil and olive oil) have UV protective property and on top of that they have natural essences. Among the natural oils, olive oil has a long history of being used as a home remedy for skincare. Olive oil is used or substituted for cleanser, moisturizer, antibacterial agent and massage reliever for muscle fatigue. It is known that sun protection factor (SPF) of olive oil is around eight. There has been relatively little scientific work performed on the effect of olive oil on the skin as sunscreen. With nanoencapsulation technique, UV light protection of the olive oil can be extended which will provide better coverage for the skin throughout the day. In the present study, natural olive oil was incorporated with DI water and surfactant (sodium dodecyl sulfate - SDS) and sonicated using probe sonicators. Sonication time, and concentrations of olive oil, DI water and surfactant were investigated in detail. The produced nanoemulsions were characterized using dynamic light scattering, and UV-Vis spectroscopy. It is believed that the nanoencupsulation of olive oil could provide better skin protection by slow releasing and deeper penetration of the nanoemulsion on skin surface. Undergraduate engineering students were involved in the project and observed all the process during the laboratory studies, as well as data collection, analysis and presentation. This experience based learning will likely enhance the students' skills and interest in the scientific and engineering studies.

  20. Nanoemulsion Formulations of Fungicide Tebuconazole for Agricultural Applications.

    PubMed

    Díaz-Blancas, Vianney; Medina, Dora I; Padilla-Ortega, Erika; Bortolini-Zavala, Raquel; Olvera-Romero, Melissa; Luna-Bárcenas, Gabriel

    2016-09-26

    Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (RO/S) were evaluated in the range of 1-90 and 1-10 wt %, respectively. The study was carried out with an organic phase (OP) consisting of an acetone/glycerol mixture containing TBZ at a concentration of 5.4 wt % and Tween 80 (TW80) as a nonionic and Agnique BL1754 (AG54) as a mixture of nonionic and anionic surfactants. The process involved a large dilution of a bicontinuous microemulsion (ME) into an aqueous phase (AP). Pseudo-ternary phase diagrams of the OP//TW80//AP and OP//AG54//AP systems at T = 25 °C were determined to map ME regions; these were in the range of 0.49-0.90, 0.01-0.23, and 0.07-0.49 of OP, AP, and surfactant, respectively. Optical microscope images helped confirm ME formation and system viscosity was measured in the range of 25-147 cP. NEs with drop sizes about 9 nm and 250 nm were achieved with TW80 and AG54, respectively. An innovative low-energy method was used to develop nanopesticide TBZ formulations based on nanoemulsion (NE) technology. The surface tension of the studied systems can be lowered 50% more than that of pure water. This study's proposed low-energy NE formulations may prove useful in sustainable agriculture.

  1. Design of a phytosphingosine-containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides.

    PubMed

    Yilmaz, Erol; Borchert, Hans-Hubert

    2005-05-01

    Positively charged oil/water (o/w) nanoemulsions (PN) are effective vehicles to change the permeability of the skin. This study focused on the preparation and characterisation of phytosphingosine (PS) containing PN (PPN) which serve as colloidal carriers for the dermal application of ceramide IIIB (CIIIB) and the stratum corneum (SC) lipids (PPNSC) such as ceramide III (CIII), cholesterol, and palmitic acid. The investigations were conducted using appropriate emulsification and homogenisation processing conditions to optimise PPNSC with regard to droplet size, physical stability, and solubility of PS, CIII and CIIIB. A decrease in droplet size was observed through eight homogenisation cycles at a pressure of 500 bar and a temperature of 50 degrees C. Above these optimal values, an increase in droplet size was observed. PS and ceramides have low solubilities in oil and water. When Lipoid E-80 (LE80) was added to the oil phase, the solubility of PS and ceramides increased, indicating some interactions shown by DSC measurements. SC lipids and CIIIB could be successfully incorporated in PPN without producing any physical instability. The high stability of PPNSC is probably due to the presence of a hydrophilic (Tween 80) and a lipophilic surfactant (LE80), supported by the lipophilic cosurfactant PS, at the o/w interface. It was shown that PS was responsible for the positive charge and thus supported the high physical stability of PPNSC. This optimised emulsion was selected for further skin absorption evaluation.

  2. Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Kundu, Amit; Sarkar, Lipi; Karmakar, Sanmoy; Jaisankar, P; Pal, Tapan Kumar

    2014-03-01

    Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Accelerated Stability Testing of a Clobetasol Propionate-Loaded Nanoemulsion as per ICH Guidelines

    PubMed Central

    Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Alam, Nawazish; Anwer, Tarique; Safhi, Mohammed Mohsen A.

    2013-01-01

    The physical and chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the objective of this work was to study the stability of clobetasol propionate (CP) in a nanoemulsion. The nanoemulsion formulation containing CP was prepared by the spontaneous emulsification method. For the formulation of the nanoemulsion, Safsol, Tween 20, ethanol, and distilled water were used. The drug was incorporated into an oil phase in 0.05% w/v. The lipophilic nature of the drug led to the O/W nanoemulsion formulation. This was characterized by droplet size, pH, viscosity, conductivity, and refractive index. Stability studies were performed as per ICH guidelines for a period of three months. The shelf life of the nanoemulsion formulation was also determined after performing accelerated stability testing (40°C ± 2°C and 75% ± 5% RH). We also performed an intermediate stability study (30°C ± 2°C/65% RH ± 5% RH). It was found that the droplet size, conductivity, and refractive index were slightly increased, while the viscosity and pH slightly decreased at all storage conditions during the 3-month period. However, the changes in these parameters were not statistically significant (p≥0.05). The degradation (%) of the optimized nanoemulsion of CP was determined and the shelf life was found to be 2.18 years at room temperature. These studies confirmed that the physical and chemical stability of CP were enhanced in the nanoemulsion formulation. PMID:24482775

  4. Ultrasound-Mediated Tumor Imaging and Nanotherapy using Drug Loaded, Block Copolymer Stabilized Perfluorocarbon Nanoemulsions

    PubMed Central

    Rapoport, Natalya; Nam, Kweon-Ho; Gupta, Roohi; Gao, Zhongao; Mohan, Praveena; Payne, Allison; Todd, Nick; Liu, Xin; Kim, Taeho; Shea, Jill; Scaife, Courtney; Parker, Dennis L.; Jeong, Eun-Kee; Kennedy, Anne M.

    2011-01-01

    Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated

  5. Comparison of Nanoemulsion and Aqueous Micelle Systems of Paliperidone for Intranasal Delivery.

    PubMed

    Pidaparthi, Kartika; Suares, Divya

    2016-10-06

    The objective of the study was to develop and compare the efficiency of nanoemulsion and aqueous micelle system of Paliperidone on intranasal administration. Both the formulations were evaluated for physical parameters such as globule size, pH, viscosity, conductivity and in vitro drug release studies. The reduction in spontaneous motor activity of L-dopa and Carbidopa-treated Swiss Albino mice on intranasal administration of nanoemulsion and micellar system of Paliperidone was compared with plain drug suspension. Histopathological evaluation of formulation treated nasal mucosal membrane was performed. Nasal spray device was evaluated for spray pattern and volume per actuation. Globule size of micellar system and nanoemulsion was found to be 16.14 & 38.25 nm, respectively. In vitro release of drug from micellar system was found to be 1.8-fold higher than nanoemulsion. The loading of drug in nanoemulsion was found to be superior (2.5 mg/mL) when compared to micellar system (0.41 mg/mL). The spray pattern of micellar system and nanoemulsion from the device was elliptical and circular, respectively. The locomotor activity of L-dopa and Carbidopa-treated Swiss albino mice was found to be 1096.5±78.49, 551.5±13.43 and 535.5±24.75 counts/min in case of plain drug suspension, micellar system and nanoemulsion, respectively. The intranasal administration of developed formulations showed significant difference (p<0.01) in the locomotor activity when compared to intranasal administration of plain drug. Thus it can be concluded that both the developed formulations have shown improved in vivo activity on intranasal administration and pose great potential for delivery of Paliperidone through intranasal route.

  6. Phase behaviour and formation of fatty acid esters nanoemulsions containing piroxicam.

    PubMed

    Mat Hadzir, Nursyamsyila; Basri, Mahiran; Abdul Rahman, Mohd Basyaruddin; Salleh, Abu Bakar; Raja Abdul Rahman, Raja Noor Zaliha; Basri, Hamidon

    2013-03-01

    Fatty acid esters are long-chain esters, produced from the reaction of fatty acids and alcohols. They possess potential applications in cosmetic and pharmaceutical formulations due to their excellent wetting behaviour at interfaces and a non-greasy feeling when applied on the skin surfaces. This preliminary work was carried out to construct pseudo-ternary phase diagrams for oleyl laurate, oleyl stearate and oleyl oleate with surfactants and piroxicam. Then, the preparation and optimization study via 'One-At-A-Time Approach' were carried out to determine the optimum amount of oil, surfactants and stabilizer using low-energy emulsification method. The results revealed that multi-phase region dominated the three pseudo-ternary phase diagrams. A composition was chosen from each multi-phase region for preparing the nanoemulsions systems containing piroxicam by incorporating a hydrocolloid stabilizer. The results showed that the optimum amount (w/w) of oil for oleyl laurate nanoemulsions was 30 and 20 g (w/w) for oleyl stearate nanoemulsions and oleyl oleate nanoemulsions. For each nanoemulsions system, the amount of mixed surfactants and stabilizer needed for the emulsification to take place was found to be 10 and 0.5 g (w/w), respectively. The emulsification process via high-energy emulsification method successfully produced nano-sized range particles. The nanoemulsions systems passed the centrifugation test and freeze-thaw cycle with no phase failures, and stable for 3 months at various storage temperatures (3°C, 25°C and 45°C). The results proved that the prepared nanoemulsions system cannot be formed spontaneously, and thus, energy input was required to produce nano-sized range particles.

  7. Accelerated Stability Testing of a Clobetasol Propionate-Loaded Nanoemulsion as per ICH Guidelines.

    PubMed

    Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Alam, Nawazish; Anwer, Tarique; Safhi, Mohammed Mohsen A

    2013-01-01

    The physical and chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the objective of this work was to study the stability of clobetasol propionate (CP) in a nanoemulsion. The nanoemulsion formulation containing CP was prepared by the spontaneous emulsification method. For the formulation of the nanoemulsion, Safsol, Tween 20, ethanol, and distilled water were used. The drug was incorporated into an oil phase in 0.05% w/v. The lipophilic nature of the drug led to the O/W nanoemulsion formulation. This was characterized by droplet size, pH, viscosity, conductivity, and refractive index. Stability studies were performed as per ICH guidelines for a period of three months. The shelf life of the nanoemulsion formulation was also determined after performing accelerated stability testing (40°C ± 2°C and 75% ± 5% RH). We also performed an intermediate stability study (30°C ± 2°C/65% RH ± 5% RH). It was found that the droplet size, conductivity, and refractive index were slightly increased, while the viscosity and pH slightly decreased at all storage conditions during the 3-month period. However, the changes in these parameters were not statistically significant (p≥0.05). The degradation (%) of the optimized nanoemulsion of CP was determined and the shelf life was found to be 2.18 years at room temperature. These studies confirmed that the physical and chemical stability of CP were enhanced in the nanoemulsion formulation.

  8. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

    PubMed Central

    Gavin, Amy; Pham, Jimmy TH; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580

  9. Effects of gelucire content on stability, macrophage interaction and blood circulation of nanoparticles engineered from nanoemulsions.

    PubMed

    Wehrung, Daniel; Geldenhuys, Werner J; Oyewumi, Moses O

    2012-06-01

    The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water nanoemulsion precursors were prepared using binary mixtures of CA and gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes of gelucire-based NPs (128-183 nm) were five times lower than control NPs (made without gelucire). All the NPs (with or without gelucire component) did not activate macrophages as monitored by reactive oxygen species production. Results from differential scanning calorimetry, FT-IR and multimodal light scattering measurements demonstrated the involvement of gelucire component in achieving homogeneous CA/gelucire particle populations that were stable on storage. The P-glycoprotein (P-gp) function assay in MES-Dx5 cells showed the potential of gelucire-based NPs in inhibiting rhodamine 123 efflux. Similarly, the extent of NP uptake by macrophage (RAW 264.7 cell) was dependent on the amount of gelucire component (inverse relationship; R(2)=0.996). NPs made with CA/gelucire mixture (at 50%, w/w gelucire) were the most effective in blood circulation studies in BALB/c mice. Additional studies with paclitaxel-loaded NPs demonstrated that the retention of gelucire-based NPs in blood circulation was comparable to NPs coated with DSPE-PEG(2000) (p>0.6). The over-all work indicated the potential efficacy of gelucire as a safe and biocompatible excipient that can serve multiple functions in enhancing the performance of lipid-based NP drug delivery systems. Published by Elsevier B.V.

  10. Skin intervention of fullerene-integrated nanoemulsion in structural and collagen regeneration against skin aging.

    PubMed

    Ngan, Cheng Loong; Basri, Mahiran; Tripathy, Minaketan; Abedi Karjiban, Roghayeh; Abdul-Malek, Emilia

    2015-04-05

    Despite the fact that intrinsic oxidative stress is inevitable, the extrinsic factor such as ultraviolet radiation enhances reactive oxygen species (ROS) generation resulting in premature skin aging. Nanoemulsion was loaded with fullerene, a strong free radical scavenger, and its efficacy to provide protection and regenerative effect against ROS-induced collagen breakdown in human skin was studied. Stable fullerene nanoemulsions were formulated using high shear homogenization and ultrasonic dispersion technique. An open trial was conducted using fullerene nanoemulsion on skin twice a day for 28 days. The mean collagen score significantly increased (P<0.05) from 36.53±4.39 to 48.69±5.46 with 33.29% increment at the end of the treatment. Biophysical characteristics of skin revealed that skin hydration was increased significantly (P<0.05) from 40.91±7.01 to 58.55±6.08 corneometric units (43.12% increment) and the water was able to contain within the stratum corneum without any increased in transepidermal water loss. In the in vitro safety evaluation, fullerene nanoemulsion showed no acute toxicity on 3T3 fibroblast cell line for 48h and no indication of potential dermal irritation. Hence, the fullerene nanoemulsion may assist in protecting collagen from breakdown with cosmeceutical benefit.

  11. Design of nanoemulsion-based delivery systems of natural antimicrobials: effect of the emulsifier.

    PubMed

    Donsì, Francesco; Annunziata, Marianna; Vincensi, Mariarosaria; Ferrari, Giovanna

    2012-06-30

    This work aims at investigating the effect of the nanoemulsion delivery systems on the antimicrobial activity of different essential oil components. Carvacrol, limonene and cinnamaldehyde were encapsulated in the sunflower oil droplets of nanoemulsions prepared by high pressure homogenization and stabilized by different emulsifiers: (a) lecithin, (b) pea proteins, (c) sugar ester and (d) a combination of Tween 20 and glycerol monooleate. The antimicrobial activity was measured against three different microorganisms, such as Escherichia coli, Lactobacillus delbrueckii and Saccharomyces cerevisiae. The measured antimicrobial activity was significantly affected by the formulation of the nanoemulsion, where the different bioactive compounds were encapsulated. In particular, the effect of the delivery systems on the antimicrobial activity was correlated to the concentration of the essential oil components in the aqueous phase in equilibrium with the nanoemulsion droplets, suggesting that the ability of the active molecules to interact with cell membranes is associated to their dissolution in the aqueous phase. These considerations can lead to a more rational design of the nanoemulsion-based delivery systems for essential oils, based on the opportune choice of the emulsifiers in dependence of the desired function of the antimicrobials within the food system. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549

    NASA Astrophysics Data System (ADS)

    Lee, W. D.; Liang, Y. J.; Chen, B. H.

    2016-12-01

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  13. Properties of active gelatin films incorporated with rutin-loaded nanoemulsions.

    PubMed

    Dammak, Ilyes; de Carvalho, Rosemary Aparecida; Trindade, Carmen Sílvia Fávaro; Lourenço, Rodrigo Vinicius; do Amaral Sobral, Paulo José

    2017-05-01

    Physico-chemical, mechanical, barrier, release profiles and antioxidant properties of composite gelatin based-films incorporated with rutin-loaded oil-in-water nanoemulsion, at various concentrations (5, 10, 15, or 20% (based on the weight of the gelatin powder)) were studied. All the gelatin/rutin-loaded nanoemulsion films displayed higher tensile strength and higher elongation at break than the gelatin control film. The composite films did not show significant differences in thickness, color, brightness and transparency. The structural properties evaluated by FTIR showed that the rutin-loaded nanoemulsion achieved complete miscibility within the gelatin matrix. All the gelatin/nanoemulsion films exhibited compact and homogenous microstructure. In addition, these films showed high antioxidant activities monitored by DPPH radical scavenging and reducing power activities. The Korsmeyer-Peppas model described well the rutin release profile. Rutin release was mainly governed by Fickian diffusion with simultaneous interfering swelling and disintegration phenomena. These results indicate that nanoemulsions-in-gelatin systems can function as potential active packaging systems to enhance shelf life of food products and then to provide a high-quality products (fresh/safe). Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Nanoemulsions as novel oral carriers of stiripentol: insights into the protective effect and absorption enhancement.

    PubMed

    Lu, Rong; Liu, Shan; Wang, Qilin; Li, Xia

    2015-01-01

    Oral administration remains a significant challenge in regards to drugs with serious solubility and stability issues. This article aimed to investigate the suitability of nanoemulsions as oral carriers of stiripentol (STP), an acid-labile drug, for enhancement of stability and bioavailability. STP-loaded nanoemulsions (STP-NEs) were prepared by using a solvent-diffusion/ultrasonication technique. STP-NEs were characterized in a variety of ways such as by particle size, entrapment efficiency, in vitro drug release, and transmission electron microscopy. A bioavailability study was performed in rats after oral administration of either STP-NEs, or commercial formulation (Diacomit). The resultant nanoemulsions were 146.6 nm in particle size with an entrapment efficiency of 99.47%. It was demonstrated that nanoemulsions significantly improved the biochemical stability and bioavailability of STP. The bioavailability of STP-NEs was up to 206.2% relative to Diacomit. Nanoemulsions fabricated from poly(ethylene glycol) monooleate/medium-chain triglycerides exhibited excellent performance in drug stabilization and absorption enhancement. The results suggest that STP-NEs are a promising means to solve the problems associated with stability and solubility of STP.

  15. Nanoemulsions as novel oral carriers of stiripentol: insights into the protective effect and absorption enhancement

    PubMed Central

    Lu, Rong; Liu, Shan; Wang, Qilin; Li, Xia

    2015-01-01

    Oral administration remains a significant challenge in regards to drugs with serious solubility and stability issues. This article aimed to investigate the suitability of nanoemulsions as oral carriers of stiripentol (STP), an acid-labile drug, for enhancement of stability and bioavailability. STP-loaded nanoemulsions (STP-NEs) were prepared by using a solvent-diffusion/ultrasonication technique. STP-NEs were characterized in a variety of ways such as by particle size, entrapment efficiency, in vitro drug release, and transmission electron microscopy. A bioavailability study was performed in rats after oral administration of either STP-NEs, or commercial formulation (Diacomit®). The resultant nanoemulsions were 146.6 nm in particle size with an entrapment efficiency of 99.47%. It was demonstrated that nanoemulsions significantly improved the biochemical stability and bioavailability of STP. The bioavailability of STP-NEs was up to 206.2% relative to Diacomit®. Nanoemulsions fabricated from poly(ethylene glycol) monooleate/medium-chain triglycerides exhibited excellent performance in drug stabilization and absorption enhancement. The results suggest that STP-NEs are a promising means to solve the problems associated with stability and solubility of STP. PMID:26261418

  16. Development and stability evaluation of olive oil nanoemulsion using sucrose monoester laurate

    NASA Astrophysics Data System (ADS)

    Eid, Ahmad M. M.; Baie, Saringat Haji; Arafat, Osama

    2012-11-01

    Nanoemulsion is a type of emulsion that consists of fine oil-in-water dispersions, with the droplets covering the size range of 20-200 nm. It can be achieved through emulsification process. One of the processes is through low energy emulsification method. Olive oil was chosen in this study due to its efficiency in treating skin problem. Olive oil nanophase gel (NPG) formulations were performed through various ratios of olive oil, sucrose laurate and glycerin. The particle sizes and stability of the prepared olive oil nanophase gel were evaluated and the optimal formulation was then selected for the development of olive oil nanoemulsion. This study proved that the composition of oil and surfactant play an important roles in influencing the nanophase gel droplet size. Nanophase gels containing olive oil in the concentration of 50 and 60 % show good stability at 4 °C and room temperature while it was less stable at 40 °C. Olive oil nanophase gels in the concentration of 50 % and 60 % with sucrose laurate 25 % in each formulation were good candidates to prepare nanoemulsion because they have the suitable droplets size and Polydispersing Index (PDI) when compared to other formulations. A mixture of NPG 50 % and water in the ratio of 40:60 and NPG 60 % and water in the ratio of 33.3:66.7 were used to produce nanoemulsions containing 20 % of oil with negative values of zeta potential (>60) which indicate the good stability of the nanoemulsions.

  17. Pharmacokinetics and pharmacodynamics of chlorambucil delivered in long-circulating nanoemulsion.

    PubMed

    Ganta, Srinivas; Sharma, Puneet; Paxton, James W; Baguley, Bruce C; Garg, Sanjay

    2010-02-01

    Chlorambucil was incorporated into a nanoemulsion modified with poly(ethylene glycol) to improve its pharmacokinetics and tissue distribution, and thus enhance its therapeutic efficacy. A long-circulating nanoemulsion (LNE) was prepared using soybean oil, egg lecithin, cholesterol and PEG(2000)DSPE. The LNE had an oil droplet size <200 nm with a surface charge of -32.2 to -35.6 mV. Approximately, 97% of the chlorambucil was encapsulated in the LNE. Intravenous (i.v.) administration of the chlorambucil LNE to C57 B/6 mice showed improved pharmacokinetic parameters with 1.4-fold higher area under the plasma concentration-time curve (AUC) and 1.3-fold longer half-life compared to a non-PEG-modified nanoemulsion, and 2.7-fold higher AUC and 7.6-fold longer half-life compared to chlorambucil solution. Tissue distribution studies after i.v. administration with LNE showed a considerable decrease in drug uptake in the reticulo-endothelial system containing organs compared to non-PEG-modified nanoemulsion. Additionally, the chlorambucil delivered in LNE significantly enhanced therapeutic efficacy in the subcutaneous colon-38 adenocarcinoma tumor mouse model with no apparent increase in toxicity. This study suggests that LNE could produce remarkably improved pharmacokinetic profile and therapeutic efficacy of chlorambucil compared to non-PEG-modified nanoemulsion and solution.

  18. Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

    PubMed

    Ferreira, Luana M; Cervi, Verônica F; Gehrcke, Mailine; da Silveira, Elita F; Azambuja, Juliana H; Braganhol, Elizandra; Sari, Marcel H M; Zborowski, Vanessa A; Nogueira, Cristina W; Cruz, Letícia

    2015-06-01

    This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.

  19. Optimization of ultrasonic emulsification conditions for the production of orange peel essential oil nanoemulsions.

    PubMed

    Hashtjin, Adel Mirmajidi; Abbasi, Soleiman

    2015-05-01

    The aim of the present study was to investigate the influence of emulsifying conditions on some physical and rheological properties of orange peel essential oil (OPEO) in water nanoemulsions. In this regard, using the response surface methodology, the influence of ultrasonication conditions including sonication amplitude (70-100 %), sonication time (90-150 s) and process temperature (5-45 °C) on the mean droplets diameter (Z-average value), polydispersity index (PDI), and viscosity of the OPEO nanoemulsions was evaluated. In addition, the flow behavior and stability of selected nanoemulsions was evaluated during storage (up to 3 months) at different temperatures (5, 25 and 45 °C). Based on the results of the optimization, the optimum conditions for producing OPEO nanoemulsions (Z-average value 18.16 nm) were determined as 94 % (sonication amplitude), 138 s (sonication time) and 37 °C (process temperature). Moreover, analysis of variance (ANOVA) showed high coefficients of determination values (R (2) > 0.95) for the response surface models of the energy input and Z-average. In addition, the flow behavior of produced nanoemulsions was Newtonian, and the effect of time and storage temperature as well as their interactions on the Z-average value was highly significant (P < 0.0001).

  20. Influence of surfactant charge on antimicrobial efficacy of surfactant-stabilized thyme oil nanoemulsions.

    PubMed

    Ziani, Khalid; Chang, Yuhua; McLandsborough, Lynne; McClements, David Julian

    2011-06-08

    Thyme oil-in-water nanoemulsions stabilized by a nonionic surfactant (Tween 80, T80) were prepared as potential antimicrobial delivery systems (pH 4). The nanoemulsions were highly unstable to droplet growth and phase separation, which was attributed to Ostwald ripening due to the relatively high water solubility of thyme oil. Ostwald ripening could be inhibited by incorporating ≥75% of corn oil (a hydrophobic material with a low water solubility) into the nanoemulsion droplets. The electrical characteristics of the droplets in the nanoemulsions were varied by incorporating ionic surfactants with different charges after homogenization: a cationic surfactant (lauric arginate, LAE) or an anionic surfactant (sodium dodecyl sulfate, SDS). The antifungal activity of nanoemulsions containing positive, negative, or neutral thymol droplets was then conducted against four strains of acid-resistant spoilage yeasts: Zygosaccharomyces bailli, Saccharomyces cerevisiae, Brettanomyces bruxellensis, and Brettanomyces naardenensis. The antifungal properties of the three surfactants (T80, LAE, SDS) were also tested in the absence of thymol droplets. Both ionic surfactants showed strong antifungal activity in the absence of thymol droplets, but no antimicrobial activity in their presence. This effect was attributed to partitioning of the antimicrobial surfactant molecules between the oil droplet and microbial surfaces, thereby reducing the effective concentration of active surfactants available to act as antimicrobials. This study shows oil droplets may decrease the efficacy of surfactant-based antimicrobials, which has important consequences for formulating effective antimicrobial agents for utilization in emulsion-based food and beverage products.

  1. The effect of nanoemulsion as a carrier of hydrophilic compound for transdermal delivery.

    PubMed

    Tsai, Ming-Jun; Fu, Yaw-Syan; Lin, Yu-Hsuan; Huang, Yaw-Bin; Wu, Pao-Chu

    2014-01-01

    The purpose of the present study was to investigate the effect of nanoemulsions as a carrier vehicle of hydrophilic drug for transdermal delivery. The response surface methodology with a mixture design was used to evaluate the effect of ingredient levels of nanoemulsion formulations including cosurfactant (isopropyl alcohol, 20 ∼ 30%), surfactant (mixed of Brij 30 and Brij 35, 20 ∼ 30%), and distilled-water (34.5 ∼ 50.0%) on properties of the drug-loaded nanoemulsions including physicochemical characters and drug permeability through rat skin. The result showed that the hydrophilic drug in aqueous solution with or without penetration enhancer could not transport across rat skin after 12 h of application. Used nanoemulsions as carrier vehicle, the permeation rate of drug was significantly increased from 0 to 63.23 µg/cm2/h and the lag time was shortened from more than 12 h to about 2.7 ∼ 4.0 h. Moreover, the drug-loaded nanoemulsion formulation also showed physicochemical stability after 3 month storage at 25°C and 40°C.

  2. Optimization of Ibuprofen Delivery through Rat Skin from Traditional and Novel Nanoemulsion Formulations.

    PubMed

    Sharif Makhmalzadeh, Behzad; Torabi, Shiva; Azarpanah, Armita

    2012-01-01

    The topical delivery of non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen has been explored as a potential method of avoiding the first pass effects and the gastric irritation, which may occur when used orally. Ibuprofen is formulated into many topical preparations to reduce the adverse effects and simultaneously avoid the hepatic first-pass metabolism as well. However, it is difficult to obtain an effective concentration through topical delivery of Ibuprofen due to its low skin permeability. The aim of this study was to develop two types of nanoemulsions formulations and focused on the screening of Ibuprofen-loaded nanoemulsions and evaluating the influence of these types of nanoemulsions on the skin permeability of the drug. In both nanoemulsion formulations, oil was similar, but the surfactant and co-surfactant were different. The effect of independent variables on skin permeability parameters was evaluated using full factorial design. Results demonstrate that novel formulations were more effective as skin enhancer than traditional formulation. In case of the novel formulation, any increase in percentage of surfactant and co-surfactant had increasing effect on flux (Jss). On the other hand, the proportion of surfactant/co-surfactant (S/C) demonstrated reverse correlation with Jss. While, in traditional formulations, direct correlation was found between both variables, and Jss. Comparison between two types of nanoemulsion formulations revealed that, novel formulations were more effective as topical Ibuprofen carrier in contrast to traditional type due to lower amounts of surfactant and co-surfactant and less irritating effect.

  3. The Effect of Nanoemulsion as a Carrier of Hydrophilic Compound for Transdermal Delivery

    PubMed Central

    Lin, Yu-Hsuan; Huang, Yaw-Bin; Wu, Pao-Chu

    2014-01-01

    The purpose of the present study was to investigate the effect of nanoemulsions as a carrier vehicle of hydrophilic drug for transdermal delivery. The response surface methodology with a mixture design was used to evaluate the effect of ingredient levels of nanoemulsion formulations including cosurfactant (isopropyl alcohol, 20∼30%), surfactant (mixed of Brij 30 and Brij 35, 20∼30%), and distilled-water (34.5∼50.0%) on properties of the drug-loaded nanoemulsions including physicochemical characters and drug permeability through rat skin. The result showed that the hydrophilic drug in aqueous solution with or without penetration enhancer could not transport across rat skin after 12 h of application. Used nanoemulsions as carrier vehicle, the permeation rate of drug was significantly increased from 0 to 63.23 µg/cm2/h and the lag time was shortened from more than 12 h to about 2.7∼4.0 h. Moreover, the drug-loaded nanoemulsion formulation also showed physicochemical stability after 3 month storage at 25°C and 40°C. PMID:25068531

  4. Antioxidant Effect of Nanoemulsions Containing Extract of Achyrocline satureioides (Lam) D.C.-Asteraceae.

    PubMed

    Zorzi, Giovanni Konat; Caregnato, Fernanda; Moreira, José Cláudio Fonseca; Teixeira, Helder Ferreira; Carvalho, Edison Luis Santana

    2016-08-01

    Ethanolic extracts of Achyrocline satureioides have pronounced antioxidant activity mainly due to the presence of the flavonoid quercetin. However, direct topical application of the extract is not possible due to the presence of high amounts of ethanol. In this sense, nanoemulsions arise as an alternative for topical formulation associating molecules with limited aqueous solubility. This article describes the development of topical nanoemulsions containing either A. satureioides extract or one of its most abundant flavonoid, quercetin. Nanoemulsions composed of octyldodecanol, egg lecithin, water and extract (NEE), or quercetin (NEQ) were prepared by spontaneous emulsification. This process led to monodisperse nanoemulsions presenting a mean droplet size of approximately 200-300 nm, negative zeta potential, and high association efficiency. A study of quercetin skin retention using porcine skin which was performed using a Franz diffusion cell revealed a higher accumulation of quercetin in skin for NEE when compared to NEQ. Finally, the antioxidant activity of formulations was measured by thiobarbituric acid-reactive species and the APPH model. A lower lipoperoxidation for the extract in respect to quercetin solution was observed. However, no difference between NEQ and NEE lipoperoxidation could be seen. The protection against lipoperoxidation by the formulations was also measured in the skin, where lower formation of reactive species was observed after treatment with NEE. In conclusion, this study shows the formulation effect on the physicochemical properties of nanoemulsions as well as on the skin retention and antioxidant activity of quercetin.

  5. Preparation, characterization and bioavailability by oral administration of O/W curcumin nanoemulsions stabilized with lysophosphatidylcholine.

    PubMed

    Chávez-Zamudio, Rubi; Ochoa-Flores, Angélica A; Soto-Rodríguez, Ida; Garcia-Varela, Rebeca; García, Hugo Sergio

    2017-09-20

    Curcumin is the main and most abundant bioactive component in Curcuma longa L. with documented properties in the prevention and treatment of chronic degenerative and infectious diseases. However, curcumin has low solubility in aqueous media, hence low bioavailability when administered orally. The use of nanoemulsions as carriers can provide a partial solution to bioavailability restrictions. In our study, O/W nanoemulsions of curcumin were prepared using lysophosphatidylcholine, a phospholipid with proven emulsification capacity; nevertheless, such qualities have not been previously reported in the preparation of nanoemulsions. Lysophosphatidylcholine was obtained by enzymatic removal of one fatty acid residue from phosphatidylcholine. The objective of our work was to formulate stable curcumin nanoemulsions and evaluate their bioavailability in BALB/c mice plasma after oral administration. Formulated nanoemulsions had a droplet size mean of 154.32 ± 3.10 nm, a polydispersity index of 0.34 ± 0.07 and zeta potential of -10.43 ± 1.10 mV; stability was monitored for 12 weeks. Lastly, in vivo pharmacokinetic parameters, using BALB/c mice, were obtained; namely, Cmax of 610 ± 65.0 μg mL(-1) and Tmax of 2 h. Pharmacokinetic data revealed a higher bioavailability of emulsified as opposed to free curcumin. Research regarding other potential emulsifiers that may provide better health benefits and carry nano-encapsulated bioactive compounds more effectively, is necessary. This study provides important data on the preparation and design of nanoencapsulated Curcumin using lysophosphatidylcholine as an emulsifier.

  6. Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis.

    PubMed

    Kaur, Amanpreet; Katiyar, Sameer S; Kushwah, Varun; Jain, Sanyog

    2017-05-01

    Current work reports the development and optimization of clobitasol propionate (CP) and calcipotriol (CT) loaded nanoemulsion based gel for topical treatment of psoriasis. Components of nanoemulsion viz., oil and surfactant/co-surfactant were selected depending upon solubility and emulsification potential respectively. The optimized ratio of 5:3:2 of Capmul MCM C8 EP, Cremophor RH 40 and Labrafil 1944 CS was selected. Carbopol 980 was used as gelling agent to achieve final drug concentration of 0.05% w/w and 0.005% w/w respectively for CP and CT. HaCaT cell lines showed higher uptake of drug from nanoemulsion in correlation with the enhancement in penetration of both drugs in stratum corneum (SC) and viable layer from nanoemulsion and gel as compared to free drugs. Imiquimod induced psoriatic BALB/c mice revealed significantly higher anti-psoriatic activity of nanoemulsion gel as compared to free drugs and marketed formulation. The developed formulation showed negligible skin irritation despite increased penetration into the skin. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Modeling and optimization of nanoemulsion containing Sorafenib for cancer treatment by response surface methodology.

    PubMed

    Izadiyan, Zahra; Basri, Mahiran; Fard Masoumi, Hamid Reza; Abedi Karjiban, Roghayeh; Salim, Norazlinaliza; Shameli, Kamyar

    2017-01-01

    The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib, which is a poorly soluble drug with no parenteral treatment. The formulation was prepared by a high energy emulsification method and optimized by response surface methodology. The effects of overhead stirring time, high shear rate, high shear time, and cycles of high-pressure homogenizer were studied in the preparation of nanoemulsion loaded with Sorafenib. Most of the particles in nanoemulsion are spherical in shape, the smallest particle size being 82.14 nm. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole reveal that the optimum formulation does not affect normal cells significantly in low drug concentrations but could remove the cancer cells. Finally, a formulation containing Sorafenib retained its properties over a period of 90 days. With characterization, the study of the formulated nanoemulsion has the potential to be used as a parenteral nanoemulsion in the treatment of cancer. Graphical abstractSchematic figure of high pressure homogenizer device.

  8. Superior antibacterial activity of nanoemulsion of Thymus daenensis essential oil against E. coli.

    PubMed

    Moghimi, Roya; Ghaderi, Lida; Rafati, Hasan; Aliahmadi, Atousa; McClements, David Julian

    2016-03-01

    Natural preservatives are being extensively investigated for their potential industrial applications in foods and other products. In this work, an essential oil (Thymus daenensis) was formulated as a water-dispersible nanoemulsion (diameter=143nm) using high-intensity ultrasound. The antibacterial activity of the essential oil in both pure and nanoemulsion forms was measured against an important food-borne pathogen bacterium, Escherichia coli. Antibacterial activity was determined by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of the essential oil against E. coli was enhanced considerably when it was converted into a nanoemulsion, which was attributed to easier access of the essential oils to the bacterial cells. The mechanism of antibacterial activity was investigated by measuring potassium, protein, and nucleic acid leakage from the cells, and electron microscopy. Evaluation of the kinetics of microbial deactivation showed that the nanoemulsion killed all the bacteria in about 5min, whereas only a 1-log reduction was observed for pure essential oil. The nanoemulsion appeared to amplify the antibacterial activity of essential oils against E. coli by increasing their ability to disrupt cell membrane integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549.

    PubMed

    Lee, W D; Liang, Y J; Chen, B H

    2016-12-09

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  10. Removal of alizarin red from aqueous solution by ethyl acetate green nanoemulsions.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Alanazi, Fars K; Alsarra, Ibrahim A

    2014-01-01

    The objective of the present study was to develop ethyl acetate (EA) green nanoemulsions for removal of alizarin red (AR) from water. Developed formulations were characterized in terms of thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity, viscosity, refractive index and per cent transmittance. Adsorption studies were performed by mixing small amounts of green nanoemulsions (1 ml) with relatively large amounts of AR solution (10 ml). It was observed that the droplet size, viscosity and % AR removal efficiency were influenced significantly by EA concentration of green nanoemulsions. However, contact time had negligible influence on % AR removal. Based on lowest droplet size (21.3 nm), lowest viscosity (19.3 Pa.s) and highest % AR removal efficiency (72.5%), green nanoemulsion E(1) containing 4.0% w/w of EA, 16.0% w/w of Triton-X100, 8.0% w/w of ethylene glycol and 72% w/w of water was optimized as the best green nanoemulsion composition for removal of AR from its bulk aqueous solution.

  11. Development of low-energy methods for preparing food Nano-emulsions.

    PubMed

    Miyanoshita, Michitaka; Hashida, Chitose; Ikeda, Shinya; Gohtani, Shoichi

    2011-01-01

    The aim of this work was to investigate the effect of sucrose on the phase behavior of vegetable oil/polyoxyethylene sorbitan monooleate (MOPS, Tween 80) and decaglycerol monolaurilester (DGML)/aqueous solution systems to establish low-energy emulsification methods for preparing nano-emulsions suitable for food uses. Phase diagrams were constructed to elucidate the optimal process for preparing the nano-emulsions. It was found that nano-emulsions were obtained when the composition was altered to either cross the sponge phase (L(3)) or lamellar phase (La) in the vegetable oil/MOPS/aqueous solution system or vegetable oil/DGML/aqueous solution system, respectively. The average droplet sizes in the former and latter emulsions were 0.203 µm and 0.165 µm, respectively. The addition of sucrose changed the hexagonal phase in the vegetable oil/MOPS/aqueous solution system into the sponge phase. As a result, the sponge region in the vegetable oil/MOPS/sucrose aqueous solution system occupied a larger area than that in the vegetable oil/MOPS/water system. In contrast, sucrose had no effect on the area of the La region in the vegetable oil/DGML/aqueous solution system. However, the addition of sucrose decreased the amount of emulsifier required to prepare nano-emulsions in both the vegetable oil/MOPS and DGML/aqueous solution systems. Sucrose was confirmed to facilitate the preparation of nano-emulsions in both systems.

  12. Physicochemical Characterization and Thermodynamic Studies of Nanoemulsion-Based Transdermal Delivery System for Fullerene

    PubMed Central

    Basri, Mahiran; Tripathy, Minaketan; Abdul-Malek, Emilia

    2014-01-01

    Fullerene nanoemulsions were formulated in palm kernel oil esters stabilized by low amount of mixed nonionic surfactants. Pseudoternary phase diagrams were established in the colloidal system of PKOEs/Tween 80 : Span 80/water incorporated with fullerene as antioxidant. Preformulation was subjected to combination of high and low energy emulsification methods and the physicochemical characteristics of fullerene nanoemulsions were analyzed using electroacoustic spectrometer. Oil-in-water (O/W) nanoemulsions with particle sizes in the range of 70–160 nm were formed. The rheological characteristics of colloidal systems exhibited shear thinning behavior which fitted well into the power law model. The effect of xanthan gum (0.2–1.0%, w/w) and beeswax (1–3%, w/w) in the estimation of thermodynamics was further studied. From the energetic parameters calculated for the viscous flow, a moderate energy barrier for transport process was observed. Thermodynamic study showed that the enthalpy was positive in all xanthan gum and beeswax concentrations indicating that the formation of nanoemulsions could be endothermic in nature. Fullerene nanoemulsions with 0.6% or higher xanthan gum content were found to be stable against creaming and flocculation when exposed to extreme environmental conditions. PMID:25165736

  13. Formulation, characterization and pharmacokinetic studies of coenzyme Q₁₀ PUFA's nanoemulsions.

    PubMed

    Belhaj, Nabila; Dupuis, François; Arab-Tehrany, Elmira; Denis, Frédéric M; Paris, Cédric; Lartaud, Isabelle; Linder, Michel

    2012-09-29

    Coenzyme Q(10) (CoQ(10)) is an insoluble antioxidant molecule with great biological value but exhibit poor bioavailability. To improve the bioavailability of CoQ(10), we have proposed to formulate a nanoemulsion consisting of salmon oil, salmon lecithin, CoQ(10) and water. A commercial oily mixture, based on soybean oil and CoQ(10), was used for comparison, as well as a second oily mixture, composed of salmon lecithin, salmon oil and CoQ(10). Salmon oil and salmon lecithin were used as sources of polyunsaturated fatty acids (PUFA). The maximum solubility of CoQ(10) in salmon oil was 81.30 ± 0.08 mg/mL at 37 °C. Mean droplets size of the control and CoQ(10) nanoemulsions was 164 and 167 nm, respectively. The nanoemulsion was stable during 30 days at 25 °C. Bioavailability was evaluated as the area under the curve of CoQ(10) plasma concentration in male Wistar rats following oral administration of the three formulations of CoQ(10). The nanoemulsion increases at twice the bioavailability of CoQ(10) than conventional oily formulations regardless the nature of used fatty acids (soybean and salmon oils). Prepared nanoemulsion represents a vectorization of both LC-PUFAs and CoQ(10). That could be an interesting way to increase the absorption of these two bioactive molecules with natural low availability.

  14. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Al-Dhfyan, Abdullah; Alanazi, Fars K; Alsarra, Ibrahim A

    2015-01-01

    Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.

  15. An Experimental Study on Flow and Heat Transfer Characteristics of Ethanol/Polyalphaolefin Nanoemulsion Flowing Through Circular Minichannels.

    PubMed

    Trinh, Vu; Xu, Jiajun

    2017-12-01

    This work experimentally studied the convective flow and heat transfer characteristics of a novel nanostructured heat transfer fluid: "ethanol/polyalphaolefin nanoemulsion" flowing through 12 circular minichannels of 1-mm diameter each. Ethanol/polyalphaolefin nanoemulsion is a thermodynamically stable system formed by dispersing ethanol into a mixture of "polyalphaolefin (PAO)" and surfactants. In this study, ethanol/PAO nanoemulsion is used as the working fluid to study the effect of ethanol nanodroplets on its convective flow and heat transfer characteristics. In addition, the effect of flow regime on its heat transfer is examined. It is found that using ethanol/PAO nanoemulsion fluids can improve convective heat transfer compared to that of pure PAO under both single- and two-phase flow regimes. For single-phase flow, there is no significant difference in Nusselt number between ethanol/PAO nanoemulsion and pure PAO in laminar flow regime. However, when entering transition flow regime, the ethanol/PAO nanoemulsion fluid showed a substantial increase in Nusselt number. Meanwhile, there is an increase in pressure drop and early onset of the laminar-turbulent transitional region for the ethanol/PAO nanoemulsion compared to pure PAO. The heat transfer coefficient of ethanol/PAO nanoemulsion can be further enhanced when the ethanol nanodroplets undergo phase change, which is hypothesized that such an effect is likely related to the enhanced interfacial thermal transport between the nanodroplets and base fluid under elevated temperature and the latent heat of phase changeable nanodroplets inside nanoemulsion. Further studies are needed to fully explore the convective heat transfer properties of nanoemulsion fluids.

  16. An Experimental Study on Flow and Heat Transfer Characteristics of Ethanol/Polyalphaolefin Nanoemulsion Flowing Through Circular Minichannels

    NASA Astrophysics Data System (ADS)

    Trinh, Vu; Xu, Jiajun

    2017-03-01

    This work experimentally studied the convective flow and heat transfer characteristics of a novel nanostructured heat transfer fluid: "ethanol/polyalphaolefin nanoemulsion" flowing through 12 circular minichannels of 1-mm diameter each. Ethanol/polyalphaolefin nanoemulsion is a thermodynamically stable system formed by dispersing ethanol into a mixture of "polyalphaolefin (PAO)" and surfactants. In this study, ethanol/PAO nanoemulsion is used as the working fluid to study the effect of ethanol nanodroplets on its convective flow and heat transfer characteristics. In addition, the effect of flow regime on its heat transfer is examined. It is found that using ethanol/PAO nanoemulsion fluids can improve convective heat transfer compared to that of pure PAO under both single- and two-phase flow regimes. For single-phase flow, there is no significant difference in Nusselt number between ethanol/PAO nanoemulsion and pure PAO in laminar flow regime. However, when entering transition flow regime, the ethanol/PAO nanoemulsion fluid showed a substantial increase in Nusselt number. Meanwhile, there is an increase in pressure drop and early onset of the laminar-turbulent transitional region for the ethanol/PAO nanoemulsion compared to pure PAO. The heat transfer coefficient of ethanol/PAO nanoemulsion can be further enhanced when the ethanol nanodroplets undergo phase change, which is hypothesized that such an effect is likely related to the enhanced interfacial thermal transport between the nanodroplets and base fluid under elevated temperature and the latent heat of phase changeable nanodroplets inside nanoemulsion. Further studies are needed to fully explore the convective heat transfer properties of nanoemulsion fluids.

  17. Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies.

    PubMed

    Thomas, Lydia; Zakir, Foziyah; Mirza, Mohd Aamir; Anwer, Md Khalid; Ahmad, Farhan Jalees; Iqbal, Zeenat

    2017-03-16

    In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1-3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm(2)/h as compared to NE2 (76.05μg/cm(2)/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing.

  18. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

    PubMed

    Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

    2014-01-02

    Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights

  19. Concurrent study of stability and cytotoxicity of a novel nanoemulsion system - an artificial neural networks approach.

    PubMed

    Seyedhassantehrani, Negar; Karimi, Roya; Tavoosidana, Gholamreza; Amani, Amir

    2017-05-01

    Problems commonly associated with using nanoemulsions are their cytotoxic effects and low stability profiles. Here, for the first time, concentrations of ingredients of a nanoemulsion system were investigated to obtain the most stable nanoemulsion system with the least cytotoxic effect on MCF7 cell line. Artificial neural networks (ANNs) were used to model the experimentally obtained data. Surfactant concentration was found to be the dominant factor in determining the stability - surfactant concentration above a critical point made the preparation unstable, while it appeared not to be influencing the cytotoxicity. Concentration of oil showed a direct relationship to the cytotoxicity with a minimum value required to provide an acceptable safety profile for the preparation. Co-surfactant appeared not to be considerably effective on neither stability nor cytotoxicity. To obtain the optimum preparation with maximum stability and minimum cytotoxicity, surfactant and oil values need to be kept at their maximum and minimum possible, respectively.

  20. Argan oil nanoemulsions as new hydrophobic drug-loaded delivery system for transdermal application.

    PubMed

    Lococo, D; Mora-Huertas, C E; Fessi, H; Zaanoun, I; Elaissari, A

    2012-10-01

    This research work deals with the development of argan oil-based nanoemulsions as vehicle of hydrophobic drugs such as diclofenac used as model. Nanoemulsions of oil in water were prepared using the ultrasonication method in order to obtain submicron size colloidal dispersion. The size, zeta potential and encapsulation efficiency of the dispersions obtained were investigated. In addition, the ability of sorbitan ester derivatives to form nanovesicles (niosomes), which in turn were used for encapsulating drug in oily solutions forming stable nanoemulsions, was particularly examined. Thus, additional stabilizing agents were not required in the recipe and formulations using only sorbitan monolaurate, argan oil and water lead to attractive results. Their submicronic size (<250 nm), high negative zeta potential (between -40 and -50 mV) and drug-encapsulation efficiency (higher than 85%) allow predicting both a good physical stability and a good performance as drug carriers.

  1. Nanoemulsion of D-limonene in water system prepared by ultrasonic emulsification.

    PubMed

    Lu, Wen-Chien; Zhang, Ting-Jie; Huang, Da-Wei; Li, Po-Hsien

    2014-01-01

    D-Limonene is a component of essential oil extracted from citrus fruits. This component has shown chemopreventive and therapeutic activity against a wide variety of experimental tumors, but D-limonene is unstable and lose its lemon-like flavor under normal storage condition, and it is almost insoluble in water. Therefore, studying the formation of nanoemulsion in D-limonene in water system is probably a good method to prevent the oxidation degradation of D-limonene. For the purpose of our study, we used mixed surfactant to form D- limonene-in-water emulsion, and found the best formula for forming nanoemulsion droplets with specified hydrophilic-lipophilic balance (HLB) value and droplet size. The results demonstrated that nanoemulsion droplets formed at So ratio of 0.4 and applied power of 18 W for 120 s under mixed surfactant at HLB values 12 and had droplet size of 20-50 nm.

  2. Synthesis of low-melting-point metallic nanoparticles with an ultrasonic nanoemulsion method.

    PubMed

    Han, Z H; Yang, B; Qi, Y; Cumings, J

    2011-05-01

    A one-step, economical nanoemulsion method has been introduced to synthesize low-melting-point metallic nanoparticles. This nanoemulsion technique exploits the extremely high shear rates generated by the ultrasonic agitation and the relatively large viscosity of the continuous phase - polyalphaolefin (PAO), to rupture the molten metal down to diameter below 100 nm. Field's metal nanoparticles and Indium nanoparticles of respective average diameters of 15 nm and 30 nm have been obtained. The nanoparticles size and shape are determined by transmission electron microscopy (TEM). Their phase transition behavior is examined using a differential scanning calorimeter (DSC). It is found that these nanoparticles dispersed in PAO can undergo reversible, melting-freezing phase transition, and exhibit a relatively large hysteresis. The experimental results suggest that the nanoemulsion method is a viable route for mass production of low-melting nanoparticles. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Structure and dynamics of nanoemulsions: Insights from combining dynamic and static neutron scattering

    NASA Astrophysics Data System (ADS)

    Hoffmann, I.; Heunemann, P.; Farago, B.; Grillo, I.; Holderer, O.; Päch, M.; Gradzielski, M.

    2012-12-01

    Despite their lack of thermodynamical stability, nanoemulsions can show a remarkable degree of kinetic stability. Among the various different preparation methods the phase-inversion concentration method is particularly interesting as it occurs spontaneously. Here we investigate such a system composed of a surfactant, cosurfactant, and oil that upon dilution with water forms long time metastable oil-in-water nanoemulsion droplets. The dynamics of the amphiphilic monolayers and its elastic properties is important for their stability and therefore the monolayer dynamics have been investigated by neutron spin echo (NSE). Despite the difficulties arising from the inherently polydisperse nature and the large number of different components necessarily contained in commercial nanoemulsion formulations, information concerning the membrane rigidity was extracted from the combination of small angle neutron scattering and NSE and several different formulations are compared. These results show that small amounts of different admixed ionic surfactants can modify the monolayer rigidity substantially and similarly effects of surface bound polyelectrolytes have been evaluated.

  4. Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.

    PubMed

    Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C

    2017-07-13

    The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Cavitation technology - a greener processing technique for the generation of pharmaceutical nanoemulsions.

    PubMed

    Sivakumar, Manickam; Tang, Siah Ying; Tan, Khang Wei

    2014-11-01

    Novel nanoemulsion-based drug delivery systems (DDS) have been proposed as alternative and effective approach for the delivery of various types of poorly water-soluble drugs in the last decade. This nanoformulation strategy significantly improves the cell uptake and bioavailability of numerous hydrophobic drugs by increasing their solubility and dissolution rate, maintaining drug concentration within the therapeutic range by controlling the drug release rate, and reducing systemic side effects by targeting to specific disease site, thus offering a better patient compliance. To date, cavitation technology has emerged to be an energy-efficient and promising technique to generate such nanoscale emulsions encapsulating a variety of highly potent pharmaceutical agents that are water-insoluble. The micro-turbulent implosions of cavitation bubbles tear-off primary giant oily emulsion droplets to nano-scale, spontaneously leading to the formation of highly uniform drug contained nanodroplets. A substantial body of recent literatures in the field of nanoemulsions suggests that cavitation is a facile, cost-reducing yet safer generation tool, remarkably highlighting its industrial commercial viability in the development of designing novel nanocarriers or enhancing the properties of existing pharmaceutical products. In this review, the fundamentals of nanoemulsion and the principles involved in their formation are presented. The underlying mechanisms in the generation of pharmaceutical nanoemulsion under acoustic field as well as the advantages of using cavitation compared to the conventional techniques are also highlighted. This review focuses on recent nanoemulsion-based DDS development and how cavitation through ultrasound and hydrodynamic means is useful to generate the pharmaceutical grade nanoemulsions including the complex double or submicron multiple emulsions.

  6. Enhanced skin permeation of glabridin using eutectic mixture-based nanoemulsion.

    PubMed

    Liu, Chen; Hu, Jin; Sui, Hong; Zhao, Qipeng; Zhang, Xia; Wang, Wenping

    2017-04-01

    This study aimed to investigate the performance of the eutectic mixture of menthol and camphor (1:1, w/w) in nanoemulsion formulation for enhanced transdermal penetration of water-insoluble glabridin. Glabridin solubility in different media was determined by a shaking bottle method. The pseudoternary phase diagrams of the oil phase (drug-loaded eutectic mixture or IPM), the surfactant (Tween 80:glycerol = 2:1, w/w), and water were constructed using the aqueous titration method. The obtained glabridin nanoemulsions were characterized and compared on their particle sizes, in vitro and in vivo penetration performance on rat skin, and storage stability. The nanoemulsion formulation was optimized as 0.25% glabridin, 5% oil phase, 10% Tween 80, 5% glycerol, and 79.75% water. The obtained nanoemulsions showed a mean droplet size of nearly 100 nm for different oil phases. And the stability of both formulations was similar after storage for 3 months. In vitro skin permeation study showed that the nanoemulsion formulation with eutectic mixture exhibited higher skin permeability (28.26 μg/cm(2)) than that with IPM (9.94 μg/cm(2)) or the drug solution formulation (3.82 μg/cm(2)), which was further confirmed by in vivo skin permeation tests on the rat skin and human skin. The eutectic mixture is a preferable solvent for glabridin, and its nanoemulsion can be used as an excellent nanocarrier for enhanced transdermal delivery of glabridin.

  7. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy.

    PubMed

    Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Alam, Nawazish; Siddiqui, Masoom Raza

    2014-01-01

    Benign prostatic hyperplasia (BPH)is the most common condition in aging men, associated with lower urinary tract symptoms. It is caused due to the augmented levels of the androgen dihydrotestosterone. Dutasteride, a 5α-Reductase inhibitor has been recommended for the treatment of BPH upon oral administration. However, long term oral administration of dutasteride may cause sexual problem in man. Therefore the main objective of this study was to develop transdermal patch having nanoemulsion gel of dutasteride in order to enhance physical and chemical stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was prepared by aqueous phase-titration method and characterized by droplet size, viscosity and refractive index. In-vitro skin permeation of dutasteride through rat abdominal skin was determined by the Franz diffusion cell.Significant increase in the steady state flux (J ss), permeability coefficient (K p) and enhancement ratio (E r) was observed in optimized nanoemulsion formulation A1 (p < 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with respect to control which indicates transdermal delivery may be better approach for BPH. Stability studies were performed for the period of 3 months. It was found that droplet size, viscosity and refractive index were slightly increased at refrigerator and room temperature in 3 months period. However, the changes in these parameters were not statistically significant (p ≥ 0.05). The shelf-life of optimized nanoemulsion A1 was found to be 2.18 years at room temperature. These results indicated that both physical as well as chemical stability of dutasteride in nanoemulsion formulation.

  8. Evaluation of a Nanoemulsion Formulation Strategy for Oral Bioavailability Enhancement of Danazol in Rats and Dogs

    PubMed Central

    Devalapally, Harikrishna; Silchenko, Svitlana; Zhou, Feng; McDade, Jessica; Goloverda, Galina; Owen, Albert; Hidalgo, Ismael J.

    2013-01-01

    The objective of this study was to determine whether nanoemulsion formulations constitute a viable strategy to improve the oral bioavailability of danazol, a compound whose poor aqueous solubility limits its oral bioavailability. Danazol-containing oil-in-water nanoemulsions (NE) with and without co-surfactants stearylamine (SA) and deoxycholic acid (DCA) were prepared and characterized. Nanoemulsion droplets size ranging from 238 to 344 nm and with surface charges of −24.8 mV (NE), −26.5 mV (NE-DCA), and +27.8 mV (NE-SA) were reproducibly obtained. Oral bioavailability of danazol in nanoemulsions was compared with other vehicles such as, PEG400, 1% methylcellulose in water (1% MC), Labrafil, and a Labrafil/Tween 80 (9:1) mixture, after intragastric administration to rats and after oral administration of NE-SA, a Labrafil solution, or a Danocrine® tablet to dogs. The absolute bioavailability of danazol was 0.6% (PEG400), 1.2% (1% MC), 6.0% (Labrafil), 7.5% (Labrafil/Tween80), 8.1% (NE-DCA), 14.8% (NE), and 17.4% (NE-SA) in rats, and 0.24% (Danocrine), 6.2% (Labrafil), and 58.7% (NE-SA) in dogs. Overall, danazol bioavailability in any nanoemulsion was higher than any other formulation. Danazol bioavailability from NE and NE-SA was 1.8 to 2.2-fold higher than NE-DCA nanoemulsion and could be due to significant difference in droplet size. PMID:23878097

  9. Ostwald Ripening Stability of Curcumin-Loaded MCT Nanoemulsion: Influence of Various Emulsifiers

    PubMed Central

    Kim, Sun-Hyung; Ji, Yeun-Sun; Lee, Eui-Seok; Hong, Soon-Taek

    2016-01-01

    Curcumin is a flavonoid found in the rhizome of the turmeric plant (Curcuma longa L.) and has recently attracted interest because it has numerous biological functions and therapeutic properties. In the present study, we attempted to incorporate curcumin into medium-chain triglyceride (MCT) nanoemulsions (0.15 wt% curcumin, 10 wt% MCT oil, and 10 wt% emulsifiers) with various emulsifiers [polyoxyethylene (20) sorbitan monolaurate (Tween-20), sorbitan monooleate (SM), and soy lecithin (SL)]. The physicochemical properties of the nanoemulsions including the Ostwald ripening stability were investigated. The initial droplet size was found to be 89.08 nm for the nanoemulsion with 10 wt% Tween-20 (control), and when Tween-20 was partially replaced with SM and SL, the size decreased: 73.43 nm with 4 wt% SM+6 wt% Tween-20 and 67.68 nm with 4 wt% SL+6 wt% Tween-20 (prepared at 15,000 psi). When the nanoemulsions were stored for 28 days at room temperature, the droplet size increased as the storage time increased. The largest increase was observed for the control nanoemulsion, followed by the 4 wt% SL+6 wt% Tween-20 and 4 wt% SM+6 wt% Tween-20 systems. The Turbiscan dispersion stability results strongly supported the relationship between droplet size and storage time. The time-dependent increase in droplet size was attributed to the Ostwald ripening phenomenon. Thus, the Ostwald ripening stability of curcumin-loaded MCT nanoemulsions with Tween-20 was considerably improved by partially replacing the Tween-20 with SM or SL. In addition, curcumin may have acted as an Ostwald ripening inhibitor. PMID:27752506

  10. Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection

    PubMed Central

    Ledet, Grace A.; Biswas, Shukla; Kumar, Vidya P.; Graves, Richard A.; Mitchner, Demaurian M.; Parker, Taylor M.; Bostanian, Levon A.; Ghosh, Sanchita P.; Mandal, Tarun K.

    2016-01-01

    The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography–mass spectroscopy (UPLC–MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at −20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation. PMID:28029115

  11. Novel paclitaxel formulations solubilized by parenteral nutrition nanoemulsions for application against glioma cell lines.

    PubMed

    Najlah, Mohammad; Kadam, Alisha; Wan, Ka-Wai; Ahmed, Waqar; Taylor, Kevin M G; Elhissi, Abdelbary M A

    2016-06-15

    The aim of this study is to investigate using nanoemulsion formulations as drug-delivery vehicles of paclitaxel (PX), a poor water-soluble anticancer drug. Two commercially available nanoemulsion fat formulations (Clinoleic 20% and Intralipid 20%) were loaded with PX and characterised based on their size, zeta potential, pH and loading efficiency. The effect of formulation on the cytotoxicity of PX was also evaluated using MTT assay. The droplet size of the Clinoleic emulsion increased from 254.1nm to 264.7nm when paclitaxel (6mg/ml) was loaded into the formulation, compared to the drug-free formulation. Similarly, the droplet size of Intralipid increased from 283.3 to 294.6nm on inclusion of 6mg/ml paclitaxel. The Polydispersity Indexes (PDIs) of all the nanoemulsion formulations (Clinoleic and Intralipid) were less than 0.2 irrespective of paclitaxel concentration indicating that all nanoemulsion formulations used were homogeneously sized. The pH range for the Clinoleic formulations (7.1-7.5) was slightly higher than that of the Intralipid formulations (6.5-6.9). The zeta potential of linoleic had a greater negative value than that of Intralipid. Loading efficiencies for paclitaxel were 70.4-80.2% and 44.2-57.4% for Clinoleic and Intralipid formulations, respectively. Clinoleic loaded with paclitaxel decreased the viability of U87-MG cell to 6.4±2.3%, compared to Intralipid loaded with paclitaxel (21.29±3.82%). Both nanoemulsions were less toxic to the normal glial cells (SVG-P12), decreasing the cell viability to 25-35%. This study suggests that nanoemulsions are useful and potentially applicable vehicles of paclitaxel for treatment of glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation.

    PubMed

    Cheng, Ying; Liu, Miao; Hu, Huijing; Liu, Daozhou; Zhou, Siyuan

    2016-04-01

    Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of -14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

  13. Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection.

    PubMed

    Ledet, Grace A; Biswas, Shukla; Kumar, Vidya P; Graves, Richard A; Mitchner, Demaurian M; Parker, Taylor M; Bostanian, Levon A; Ghosh, Sanchita P; Mandal, Tarun K

    2016-12-24

    The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

  14. Preparation, Characterization and Stability Study of Dutasteride Loaded Nanoemulsion for Treatment of Benign Prostatic Hypertrophy

    PubMed Central

    Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Alam, Nawazish; Siddiqui, Masoom Raza

    2014-01-01

    Benign prostatic hyperplasia (BPH)is the most common condition in aging men, associated with lower urinary tract symptoms. It is caused due to the augmented levels of the androgen dihydrotestosterone. Dutasteride, a 5α-Reductase inhibitor has been recommended for the treatment of BPH upon oral administration. However, long term oral administration of dutasteride may cause sexual problem in man. Therefore the main objective of this study was to develop transdermal patch having nanoemulsion gel of dutasteride in order to enhance physical and chemical stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was prepared by aqueous phase-titration method and characterized by droplet size, viscosity and refractive index. In-vitro skin permeation of dutasteride through rat abdominal skin was determined by the Franz diffusion cell.Significant increase in the steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) was observed in optimized nanoemulsion formulation A1 (p < 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with respect to control which indicates transdermal delivery may be better approach for BPH. Stability studies were performed for the period of 3 months. It was found that droplet size, viscosity and refractive index were slightly increased at refrigerator and room temperature in 3 months period. However, the changes in these parameters were not statistically significant (p ≥ 0.05). The shelf-life of optimized nanoemulsion A1 was found to be 2.18 years at room temperature. These results indicated that both physical as well as chemical stability of dutasteride in nanoemulsion formulation. PMID:25587300

  15. Tunable stability of monodisperse secondary O/W nano-emulsions

    NASA Astrophysics Data System (ADS)

    Vecchione, R.; Ciotola, U.; Sagliano, A.; Bianchini, P.; Diaspro, A.; Netti, P. A.

    2014-07-01

    Stable and biodegradable oil in water (O/W) nano-emulsions can have a huge impact on a wide range of bio-applications, from food to cosmetics and pharmaceuticals. Emulsions, however, are immiscible systems unstable over time; polymer coatings are known to be helpful, but an effective procedure to stabilize monodisperse and biodegradable O/W nano-emulsions is yet to be designed. Here, we coat biodegradable O/W nano-emulsions with a molecular layer of biodegradable polyelectrolytes such as polysaccharides - like chitosan - and polypeptides - like polylysine - and effectively re-disperse and densify the polymer coating at high pressure, thus obtaining monodisperse and stable systems. In particular, focusing on chitosan, our tests show that it is possible to obtain unprecedented ultra-stable O/W secondary nano-emulsions (diameter sizes tunable from ~80 to 160 nm and polydispersion indices below 0.1) by combining this process with high concentrations of polymers. Depending on the polymer concentration, it is possible to control the level of coating that results in a tunable stability ranging from a few weeks to several months. The above range of concentrations has been investigated using a fluorescence-based approach with new insights into the coating evolution.Stable and biodegradable oil in water (O/W) nano-emulsions can have a huge impact on a wide range of bio-applications, from food to cosmetics and pharmaceuticals. Emulsions, however, are immiscible systems unstable over time; polymer coatings are known to be helpful, but an effective procedure to stabilize monodisperse and biodegradable O/W nano-emulsions is yet to be designed. Here, we coat biodegradable O/W nano-emulsions with a molecular layer of biodegradable polyelectrolytes such as polysaccharides - like chitosan - and polypeptides - like polylysine - and effectively re-disperse and densify the polymer coating at high pressure, thus obtaining monodisperse and stable systems. In particular, focusing on

  16. Pterodon emarginatus oleoresin-based nanoemulsion as a promising tool for Culex quinquefasciatus (Diptera: Culicidae) control.

    PubMed

    Oliveira, Anna E M F M; Duarte, Jonatas L; Cruz, Rodrigo A S; Souto, Raimundo N P; Ferreira, Ricardo M A; Peniche, Taires; da Conceição, Edemilson C; de Oliveira, Leandra A R; Faustino, Silvia M M; Florentino, Alexandro C; Carvalho, José C T; Fernandes, Caio P

    2017-01-03

    Preparation of nanoformulations using natural products as bioactive substances is considered very promising for innovative larvicidal agents. On this context, oil in water nanoemulsions develop a main role, since they satisfactorily disperse poor-water soluble substances, such as herbal oils, in aqueous media. Pterodon emarginatus, popularly known as sucupira, has a promising bioactive oleoresin. However, to our knowledge, no previous studies were carried out to evaluate its potential against Culex quinquefasciatus, the main vector of the tropical neglected disease called lymphatic filariasis or elephantiasis. Thus, we aimed to investigate influence of different pairs of surfactants in nanoemulsion formation and investigate if a sucupira oleoresin-based nanoemulsion has promising larvicidal activity against this C. quinquefasciatus. We also evaluated morphological alteration, possible mechanism of insecticidal action and ecotoxicity of the nanoemulsion against a non-target organism. Among the different pairs of surfactants that were tested, nanoemulsions obtained with polysorbate 80/sorbitan monooleate and polysorbate 80/sorbitan trioleate presented smallest mean droplet size just afterwards preparation, respectively 151.0 ± 2.252 and 160.7 ± 1.493 nm. They presented high negative zeta potential values, low polydispersity index (<0.300) and did not present great alteration in mean droplet size and polydispersity index after 1 day of preparation. Overall, nanoemulsion prepared with polysorbate 80/sorbitan monooleate was considered more stable and was chosen for biological assays. It presented low LC50 value against larvae (34.75; 7.31-51.86 mg/L) after 48 h of treatment and some morphological alteration was observed. The nanoemulsion did not inhibit acetylcholinesterase of C. quinquefasciatus larvae. It was not toxic to green algae Chlorella vulgaris at low concentration (25 mg/L). Our results suggest that optimal nanoemulsions may be prepared with

  17. Atmospheric air-plasma treatment of polyester fiber to improve the performance of nanoemulsion silicone

    NASA Astrophysics Data System (ADS)

    Parvinzadeh, Mazeyar; Ebrahimi, Izadyar

    2011-02-01

    Influence of atmospheric air plasma treatment on performance of nanoemulsion silicone softener on polyethylene terephthalate fibers was investigated by the use of fourier transform infrared spectroscopy (FTIR), bending lengths (BL), wrinkle recovery angles (WRA), fiber friction coefficient analysis (FFCA), moisture absorbency (MA), scanning electron microscopy (SEM) and reflectance spectroscopy (RS). Results indicated that the plasma pretreatment modifies the surface of fibers and increases the reactivity of substrate toward nanoemulsion silicone. Moisture regain and microscopic tests showed that the combination of plasma and silicone treatments on polyethylene terephthalate can decrease moisture absorption due to uniform coating of silicone emulsion on surface of fibers.

  18. Irreversible shear-induced vitrification of droplets into elastic nanoemulsions by extreme rupturing

    SciTech Connect

    Wilking, James N.; Mason, Thomas G.

    2007-04-15

    Many materials weaken through fracturing when subjected to extreme stresses. By contrast, we show that breaking down repulsive bits of matter dispersed in a viscous liquid can cause a dramatic and irreversible increase in the dispersion's elasticity. Anionically stabilized microscale emulsions subjected to a history of high-pressure microfluidic flow can develop an unusually large elastic modulus as droplets are ruptured to the nanoscale, yielding 'nanonaise'. As the droplet size approaches the Debye screening length, the nanoemulsion vitrifies. Consequently, the onset of elasticity for disordered uniform nanoemulsions can occur at droplet volume fractions far below maximal random jamming of spheres.

  19. Eucalyptus oil nanoemulsion-impregnated chitosan film: antibacterial effects against a clinical pathogen, Staphylococcus aureus, in vitro

    PubMed Central

    Sugumar, Saranya; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Eucalyptus oil (Eucalyptus globulus) nanoemulsion was formulated using low-and high-energy emulsification methods. Development of nanoemulsion was optimized for system parameters such as emulsifier type, emulsifier concentration, and emulsification methods to obtain a lower droplet size with greater stability. The minimized droplet diameter was achieved using the high-energy method of ultrasonication. Tween 80 was more effective in reducing droplet size and emulsion appearance when compared to Tween 20. Stable nanoemulsion was formulated with Tween 80 as a surfactant, and the particle size was found to be 9.4 nm (1:2 v/v). The eucalyptus oil nanoemulsion was impregnated into chitosan (1%) as a biopolymer in varying concentrations. Further, the film was characterized by moisture content, microscopic study, X-ray diffraction, and Fourier transform infrared spectroscopy. Also, the film with and without nanoemulsion was evaluated against Staphylococcus aureus. The nanoemulsion-impregnated chitosan film showed higher antibacterial activity than chitosan film. These results support the inclusion of nanoemulsion-impregnated chitosan film in wound management studies. PMID:26491308

  20. Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of Rapanea ferruginea

    PubMed Central

    Dal Mas, Juarana; Zermiani, Tailyn; Thiesen, Liliani C; Silveira, Joana LM; da Silva, Kathryn ABS; de Souza, Márcia M; Malheiros, Angela; Bresolin, Tania MB; Lucinda-Silva, Ruth M

    2016-01-01

    The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88±8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was −34.7±1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10±0.08 and 53.03 μg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity. PMID:27660442

  1. Multimodal Perfluorocarbon Nanoemulsions for 19F MRI, Ultrasonography, and Catalysis of MRgFUS-Mediated Drug Delivery

    NASA Astrophysics Data System (ADS)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Parker, D. L.; Payne, A. H.; Todd, N.; Shea, J. E.; Scaife, C. L.

    2011-09-01

    Perfluorocarbon nanoemulsions can target lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent droplet-to-bubble transition upon injection that was hard to control. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. The size of paclitaxel-loaded PFCE nanodroplets (300 nm to 500 nm depending on emulsification conditions) favors their passive accumulation in tumor tissue. PFCE nanodroplets manifest both ultrasound and 19F MR contrast properties, which allows the use of multimodal imaging to monitor nanodroplet biodistribution. Ultrasonography and 19F MRI produced consistent results on nanodroplet biodistribution. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization underwent stable cavitation. In a pilot study on ultrasound-mediated therapy of a large breast cancer tumor, paclitaxel-loaded PFCE nanoemulsions combined with 1-MHz ultrasound (MI≥1.75) showed excellent therapeutic properties. Anticipated mechanisms of the observed effects are discussed.

  2. Eucalyptus oil nanoemulsion-impregnated chitosan film: antibacterial effects against a clinical pathogen, Staphylococcus aureus, in vitro.

    PubMed

    Sugumar, Saranya; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Eucalyptus oil (Eucalyptus globulus) nanoemulsion was formulated using low-and high-energy emulsification methods. Development of nanoemulsion was optimized for system parameters such as emulsifier type, emulsifier concentration, and emulsification methods to obtain a lower droplet size with greater stability. The minimized droplet diameter was achieved using the high-energy method of ultrasonication. Tween 80 was more effective in reducing droplet size and emulsion appearance when compared to Tween 20. Stable nanoemulsion was formulated with Tween 80 as a surfactant, and the particle size was found to be 9.4 nm (1:2 v/v). The eucalyptus oil nanoemulsion was impregnated into chitosan (1%) as a biopolymer in varying concentrations. Further, the film was characterized by moisture content, microscopic study, X-ray diffraction, and Fourier transform infrared spectroscopy. Also, the film with and without nanoemulsion was evaluated against Staphylococcus aureus. The nanoemulsion-impregnated chitosan film showed higher antibacterial activity than chitosan film. These results support the inclusion of nanoemulsion-impregnated chitosan film in wound management studies.

  3. Intranasal brain delivery of cationic nanoemulsion-encapsulated TNFα siRNA in prevention of experimental neuroinflammation.

    PubMed

    Yadav, Sunita; Gandham, Srujan K; Panicucci, Riccardo; Amiji, Mansoor M

    2016-05-01

    Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsion encapsulating an anti-TNFα siRNA, for potential anti-inflammatory therapy. TNFα siRNA nanoemulsions were prepared and characterized for particle size, surface charge, morphology, and stability and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed higher uptake compared to Lipofectamine® transfected siRNA. Nanoemulsion significantly lowered TNFα levels in LPS-stimulated cells. Upon intranasal delivery of cationic nanoemulsions almost 5 fold higher uptake was observed in the rat brain compared to non-encapsulated siRNA. More importantly, intranasal delivery of TNFα siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNFα in an LPS-induced model of neuroinflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNFα siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation. Neuroinflammation is often seen in patients with neurodegenerative disorders and tumor necrosis factor-alpha (TNFα) plays a significant role in contributing to neuronal dysfunction. As a result, inhibition of TNFα may alleviate disease severity. In this article, the authors investigated using a cationic nanoemulsion system carrying TNFα siRNA intra-nasally to protect against neuroinflammation. This new method may provide a future approach in this clinical setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Intranasal Brain Delivery of Cationic Nanoemulsion-Encapsulated TNFα siRNA in Prevention of Experimental Neuroinflammation

    PubMed Central

    Yadav, Sunita; Gandham, Srujan K.; Panicucci, Riccardo; Amiji, Mansoor M.

    2016-01-01

    Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. Activated microglia and secreted factors such as tumor necrosis factor-alpha (TNFα) are key mediators of neuroinflammation and may contribute to neuronal dysfunction. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsions encapsulating an anti-TNFα siRNA, for potential anti-inflammatory therapy, tested in an LPS induced model of neuroinflammation. The strategy of developing a cationic nanoemulsion system for silencing the TNFα gene was to efficiently provide neuroprotection against inflammation. TNFα siRNA nanoemulsions were prepared and characterized for particle size, surface charge, morphology, and stability and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed higher uptake compared to Lipofectamine® transfected siRNA. Nanoemulsions showed significantly lower (p<0.01) levels of TNFα in LPS-stimulated cells. Upon intranasal delivery of cationic nanoemulsions almost 5 fold higher uptake was observed in the rat brain compared to non-encapsulated siRNA. More importantly, intranasal delivery of TNFα siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNFα in an LPS-induced model of neuroinflammation where TNFα functions as a signaling molecule, which aggravates inflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNFα siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation. PMID:26767514

  5. Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of Rapanea ferruginea.

    PubMed

    Dal Mas, Juarana; Zermiani, Tailyn; Thiesen, Liliani C; Silveira, Joana Lm; da Silva, Kathryn Abs; de Souza, Márcia M; Malheiros, Angela; Bresolin, Tania Mb; Lucinda-Silva, Ruth M

    The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88±8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was -34.7±1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10±0.08 and 53.03 μg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity.

  6. Nanoemulsion of ethanolic extracts of propolis and its antioxidant activity

    NASA Astrophysics Data System (ADS)

    Mauludin, R.; Primaviri, D. S.; Fidrianny, I.

    2015-09-01

    Propolis contains several antioxidant compounds which can be used in topical application to protect skin against free radical and prevent skin cancer and skin aging. Ethanolic extracts of propolis (EEP) provided the greatest antioxidant activity but has very small solubility in water thus was prepared in nanoemulsion (NE). EEP contains steroid/triterpenoid, flavonoid, and saponin. EEP had the value of DPPH scavenging activity 61.14% and IC50 0.41629 ppm. The best NE formulation consisted of 26.25% Kolliphor RH40; 8.75% glycerin; 5% rice bran oil; and 3% EEP. NE was transparent, had particle size of 23.72 nm and polydispersity index of 0.338. Based on TEM morphology, NE was almost spherical and has particle size below 50 nm. NE propolis revealed to be physically stable after stability test within 63 days at 25°C and passed 6 cycles of Freeze and Thaw test without separated. NE propolis reduced around 58% of free radical DPPH similar to antioxidant activity of the original extracts. Antioxidant activity of NE propolis is relatively stable after stored for 6 weeks. NE propolis was proven to be safe by primary irritation test with the value of primary irritation index (OECD) was 0.

  7. Optimization of orange oil nanoemulsion formation by isothermal low-energy methods: influence of the oil phase, surfactant, and temperature.

    PubMed

    Chang, Yuhua; McClements, David Julian

    2014-03-12

    Nanoemulsions are particularly suitable as a platform in the development of delivery systems for lipophilic functional agents. This study shows that transparent orange oil nanoemulsions can be fabricated using an isothermal low-energy method (spontaneous emulsification), which offers the advantage of fabricating flavor oil delivery systems using rapid and simple processing operations. Orange oil nanoemulsions were formed spontaneously by titration of a mixture of orange oil, carrier oil [medium-chain triglyceride (MCT)], and non-ionic surfactant (Tween) into an aqueous solution (5 mM citrate buffer at pH 3.5) with continuous stirring. The oil/emulsion ratio content was kept constant (10 wt %), while the surfactant/emulsion ratio (SER) was varied (2.5-20 wt %). Oil-phase composition (orange oil/MCT ratio), SER, and surfactant type all had an appreciable effect on nanoemulsion formation and stability. Transparent nanoemulsions could be formed under certain conditions: 20% surfactant (Tween 40, 60, or 80) and 10% oil phase (4-6% orange oil + 6-4% MCT). Surfactant type and oil-phase composition also affected the thermal stability of the nanoemulsions. Most of the nanoemulsions broke down after thermal cycling (from 20 to 90 °C and back to 20 °C); however, one system remained transparent after thermal cycling: 20% Tween 80, 5% orange oil, and 5% MCT. The mean droplet size of these nanoemulsions increased over time, but the droplet growth rate was reduced appreciably after dilution. These results have important implications for the design and utilization of nanoemulsions as delivery systems in the food and other industries.

  8. Characterization and side effect analysis of a newly designed nanoemulsion targeting human serum albumin for drug delivery.

    PubMed

    Divsalar, Adeleh; Saboury, Ali Akbar; Nabiuni, Mohammad; Zare, Zohre; Kefayati, Mohammad Esmaeil; Seyedarabi, Arefeh

    2012-10-01

    Human serum albumin (HSA), the most abundant protein in plasma, plays an important role in the transportation of metabolic and exogenous compounds, particularly drugs. However, it takes a carrier to bring the metabolite or compound to the plasma for subsequent transportation in blood using HSA. A nanoemulsion which constitutes a mixture of two immiscible liquid phases can act as an effective drug carrier due to its unique properties. In this study, we report the characterization results of a newly designed nanoemulsion via dynamic light scattering (DLS) and scanning electron microscopy (SEM), followed by results on the alterations in the structure of HSA upon interaction with the nanoemulsion using circular dichroism (CD) as well as intrinsic and extrinsic fluorescence spectroscopy methods at ambient and physiological temperatures. Results of SEM and DLS show that particles making up the nanoemulsion have a nearly monodisperse size distribution and spherical morphology. Results of intrinsic fluorescence spectroscopy show decreasing emission intensity with increasing nanoemulsion concentration. Results from this study using 1-anilino-8-naphthalene sulfonic acid (ANS) confirm the intrinsic fluorescence data and reveal that adding the nanoemulsion to HSA leads to an increase in fluorescence intensity. These results imply that the interaction between the nanoemulsion and HSA cause a structural transformation in which native HSA turns "inside out" to expose its hydrophobic core to the surrounding environment. Far-UV-CD results indicate that the nanoemulsion induces a loss in α-helical structure of the HSA protein. In summary, the exposure of the blood carrier protein HSA to a newly designed nanoemulsion resulted in significant alterations of protein structure and conformation depicted by a red shift in maximum fluorescence intensity, decreased α-helical structure, and increased exposure of nonpolar or accessible hydrophobic surface of HSA to the solvent. Crown

  9. Ultrasound processed nanoemulsion: A comparative approach between resveratrol and resveratrol cyclodextrin inclusion complex to study its binding interactions, antioxidant activity and UV light stability.

    PubMed

    Kumar, Raj; Kaur, Khushwinder; Uppal, Shivani; Mehta, S K

    2017-07-01

    Resveratrol is a naturally occurring therapeutic molecule used for treatment of diseases caused by oxidative stress. This investigation elucidates the advantages of fabrication of size controlled resveratrol inclusion complex. This has been done by encapsulating resveratrol-cyclodextrin inclusion complex in a phospholipid stabilized nanoemulsion formulated by ultrasonication emulsification method. The prepared nanoemulsion has been compared with resveratrol encapsulated nanoemulsion system. The morphology of the resveratrol nanoemulsion and inclusion complex nanoemulsion have been observed using transmission electron microscopy with average size 20.41±3.41 and 24.48±5.70nm respectively. The nanoemulsion showed good loading and release efficiency. The radical diminishing potential of resveratrol and its inclusion complex has been compared in nanoemulsion. The effect of UV irradiation (365nm) on resveratrol in different solvent systems (ethanol, water and nanoemulsion) indicated that nanoemulsion prevents degradation of resveratrol. Efforts have also been made to explore the interactions between bovine serum albumin and resveratrol in nanoemulsion. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evaluation of transdermal delivery of nanoemulsions in ex vivo porcine skin using two-photon microscopy and confocal laser-scanning microscopy.

    PubMed

    Choi, Sanghoon; Kim, Jin Woong; Lee, Yong Joong; Delmas, Thomas; Kim, Changhwan; Park, Soyeun; Lee, Ho

    2014-01-01

    This study experimentally evaluates the self-targeting ability of asiaticoside-loaded nanoemulsions compared with nontargeted nanoemulsions in ex vivo experiments with porcine skin samples. Homebuilt two-photon and confocal laser-scanning microscopes were employed to noninvasively examine the transdermal delivery of two distinct nanoemulsions. Prior to the application of nanoemulsions, we noninvasively observed the morphology of porcine skin using two-photon microscopy. We have successfully visualized the distributions of the targeted and nontargeted nanoemulsions absorbed into the porcine skin samples. Asiaticoside-loaded nanoemulsions showed an improved ex vivo transdermal delivery through the stratum corneum compared with nonloaded nanoemulsions. As a secondary measure, nanoemulsions-applied samples were sliced in the depth direction with a surgical knife in order to obtain the complete depth-direction distribution profile of Nile red fluorescence. XZ images demonstrated that asiaticoside-loaded nanoemulsion penetrated deeper into the skin compared with nontargeted nanoemulsions. The basal layer boundary is clearly visible in the case of the asiaticoside-loaded skin sample. These results reaffirm the feasibility of using self-targeting ligands to improve permeation through the skin barrier for cosmetics and topical drug applications.

  11. Evaluation of transdermal delivery of nanoemulsions in ex vivo porcine skin using two-photon microscopy and confocal laser-scanning microscopy

    NASA Astrophysics Data System (ADS)

    Choi, Sanghoon; Kim, Jin Woong; Lee, Yong Joong; Delmas, Thomas; Kim, Changhwan; Park, Soyeun; Lee, Ho

    2014-10-01

    This study experimentally evaluates the self-targeting ability of asiaticoside-loaded nanoemulsions compared with nontargeted nanoemulsions in ex vivo experiments with porcine skin samples. Homebuilt two-photon and confocal laser-scanning microscopes were employed to noninvasively examine the transdermal delivery of two distinct nanoemulsions. Prior to the application of nanoemulsions, we noninvasively observed the morphology of porcine skin using two-photon microscopy. We have successfully visualized the distributions of the targeted and nontargeted nanoemulsions absorbed into the porcine skin samples. Asiaticoside-loaded nanoemulsions showed an improved ex vivo transdermal delivery through the stratum corneum compared with nonloaded nanoemulsions. As a secondary measure, nanoemulsions-applied samples were sliced in the depth direction with a surgical knife in order to obtain the complete depth-direction distribution profile of Nile red fluorescence. XZ images demonstrated that asiaticoside-loaded nanoemulsion penetrated deeper into the skin compared with nontargeted nanoemulsions. The basal layer boundary is clearly visible in the case of the asiaticoside-loaded skin sample. These results reaffirm the feasibility of using self-targeting ligands to improve permeation through the skin barrier for cosmetics and topical drug applications.

  12. Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of vernix caseosa lipids.

    PubMed

    Rissmann, Robert; Oudshoorn, Marion H M; Kocks, Elise; Hennink, Wim E; Ponec, Maria; Bouwstra, Joke A

    2008-10-01

    The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters--the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.

  13. Analysis of anti-neoplastic drug in bacterial ghost matrix, w/o/w double nanoemulsion and w/o nanoemulsion by a validated 'green' liquid chromatographic method.

    PubMed

    Youssof, Abdullah M E; Salem-Bekhit, Mounir M; Shakeel, Faiyaz; Alanazi, Fars K; Haq, Nazrul

    2016-07-01

    The objective of the present investigation was to develop and validate a 'green' reversed phase high-performance liquid chromatography (RP-HPLC) method for rapid analysis of a cytotoxic drug 5-fluorouracil (5-FU) in bulk drug, marketed injection, water-in-oil (w/o) nanoemulsion, double water-in-oil-in-water (w/o/w) nanoemulsion and bacterial ghost (BG) matrix. The chromatography study was carried out at room temperature (25±1°C) using an HPLC system with the help of ultraviolet (UV)-visible detector. The chromatographic performance was achieved with a Nucleodur 150mm×4.6mm RP C8 column filled with 5µm filler as a static phase. The mobile phase consisted of ethyl acetate: methanol (7:3% v/v) which was delivered at a flow rate of 1.0mLmin(-1) and the drug was detected in UV mode at 254nm. The developed method was validated in terms of linearity (r(2)=0.998), accuracy (98.19-102.09%), precision (% RSD=0.58-1.17), robustness (% RSD=0.12-0.53) and sensitivity with satisfactory results. The efficiency of the method was demonstrated by the assay of the drug in marketed injection, w/o nanoemulsion, w/o/w nanoemulsion and BG with satisfactory results. The successful resolution of the drug along with its degradation products clearly established the stability-indicating nature of the proposed method. Overall, these results suggested that the proposed analytical method could be effectively applied to the routine analysis of 5-FU in bulk drug, various pharmaceutical dosage forms and BG. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Preparation and in vitro /ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone

    NASA Astrophysics Data System (ADS)

    Patel, Mrunali R.; Patel, Mitali H.; Patel, Rashmin B.

    2016-11-01

    Paliperidone was formulated in mucoadhesive nanoemulsion with the aim of improving its solubility and transnasal delivery, which can further utilized for its preclinical evaluation. Solubility of Paliperidone in oils, emulsifiers, co-emulsifiers was determined to identify nanoemulsion components. Emulsifier and co-emulsifiers were screened for their ability to emulsify selected oily phase. Phase diagrams were constructed to identify the area of nanoemulsification. Paliperidone nanoemulsion was formulated using spontaneous nanoemulsification method. The three nanoemulsions (PMNE4, PMNE5, and PMNE6) containing 5.71-6.80 % oleic acid as an oily phase, 47.62-51.63 % labrasol and plurol oleique CC 497 as emulsifier mixture (1:1), 42.86-45.58 % (wt/wt) aqueous phase having a suitable optical transparency of 98.33-99.33 %, globule size of 28.8-43.2 nm and polydispersity of 0.129-0.152 were selected for the incorporation of mucoadhesive polymer. The PMNE6 showed highest flux (5.072 ± 0.13 µg/cm2/min) with enhancement ratio of 1.1 as compared to Paliperidone solution (PS). The diffusion co-efficient of PMNE6 was significantly higher than PMNE5, PMNE4 and PS and followed higuchi model. The formulation was found to be free from nasal cilio toxicity. All formulations were found to be stable for 6 months at room temperature.

  15. Benefits of cetalkonium chloride cationic oil-in-water nanoemulsions for topical ophthalmic drug delivery

    PubMed Central

    Daull, Philippe; Lallemand, Frédéric; Garrigue, Jean-Sébastien

    2014-01-01

    Objectives Topical ocular administration is the most convenient route of administration of drugs for the treatment of eye diseases. However, the bioavailability of drugs following eye instillations of eye drops is very low. Over the past 20 years, extensive efforts have been put into research to improve drug bioavailability without compromising treatment compliance and patients' quality of life. Key findings One of the most efficient ways to improve drug bioavailability is to increase the precorneal residence time of the eye drop formulations. As a result, new eye drops, with bioadhesive properties, have been developed based on the cationic oil-in-water (o/w) nanoemulsion technology. These low viscosity eye drop nanoemulsions have improved precorneal residence time through the electrostatic interactions between the positively charged oil nanodroplets and the negatively charged ocular surface epithelium. Summary This review is the first to present the benefits of this new strategy used to improve ocular drug bioavailability. The roles of the cationic agent in the stabilization of a safe cationic o/w nanoemulsion have been discussed, as well as the unexpected benefits of the cationic o/w nanoemulsion for the protection and restoration of a healthy tear film and corneal epithelium. PMID:24001405

  16. Thermal conductivity and viscosity of self-assembled alcohol/polyalphaolefin nanoemulsion fluids

    PubMed Central

    2011-01-01

    Very large thermal conductivity enhancement had been reported earlier in colloidal suspensions of solid nanoparticles (i.e., nanofluids) and more recently also in oil-in-water emulsions. In this study, nanoemulsions of alcohol and polyalphaolefin (PAO) are spontaneously generated by self-assembly, and their thermal conductivity and viscosity are investigated experimentally. Alcohol and PAO have similar thermal conductivity values, so that the abnormal effects, such as particle Brownian motion, on thermal transport could be deducted in these alcohol/PAO nanoemulsion fluids. Small angle neutron-scattering measurement shows that the alcohol droplets are spheres of 0.8-nm radius in these nanoemulsion fluids. Both thermal conductivity and dynamic viscosity of the fluids are found to increase with alcohol droplet loading, as expected from classical theories. However, the measured conductivity increase is very moderate, e.g., a 2.3% increase for 9 vol%, in these fluids. This suggests that no anomalous enhancement of thermal conductivity is observed in the alcohol/PAO nanoemulsion fluids tested in this study. PMID:21711807

  17. Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

    PubMed

    Davidov-Pardo, Gabriel; McClements, David Julian

    2015-01-15

    The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Stability of orange oil/water nanoemulsions prepared by the PIT method.

    PubMed

    Souza, Verônica B; Almeida, Sarah M; Spinelli, Luciana S; Mansur, Claudia R E

    2011-03-01

    This article reports the preparation and characterization of orange oil/water nanoemulsions stabilized by commercial nonionic surfactants based on ethoxylated lauryl ether (Ultrol line), by the phase inversion temperature (PIT) method. The orange oil/surfactant/water dispersions were prepared at different HLB values, by varying the concentrations of the surfactants as well as the concentration of the oil phase. The stability of the o/w nanoemulsions and the size distribution of the dispersed particles in these systems in general depended on the concentration of the oil phase used: the emulsions prepared with an oil phase of 14 wt% had smaller droplet size in the dispersed phase than the emulsions prepared in the presence of oil phases of 20 and 30 wt%. The nanoemulsions prepared with pure surfactants were more stable in the presence of Ultrol L60, but the surfactants' cloud point had a strong influence on the stability of the emulsions formed when this was very near room temperature. Because of this, we prepared systems containing mixtures of surfactants. Among these systems, the most stable nanoemulsions were those prepared with a Ultrol L100/Ultrol L20 mixture with HLB of 12.40. This behavior can be attributed to the complete solubilization in mixed micelles of the more hydrophobic surfactant.

  19. Bactericidal action mechanism of negatively charged food grade clove oil nanoemulsions.

    PubMed

    Majeed, Hamid; Liu, Fei; Hategekimana, Joseph; Sharif, Hafiz Rizwan; Qi, Jing; Ali, Barkat; Bian, Yuan-Yuan; Ma, Jianguo; Yokoyama, Wallace; Zhong, Fang

    2016-04-15

    Clove oil (CO) anionic nanoemulsions were prepared with varying ratios of CO to canola oil (CA), emulsified and stabilized with purity gum ultra (PGU), a newly developed succinylated waxy maize starch. Interfacial tension measurements showed that CO acted as a co-surfactant and there was a gradual decrease in interfacial tension which favored the formation of small droplet sizes on homogenization until a critical limit (5:5% v/v CO:CA) was reached. Antimicrobial activity of the negatively charged CO nanoemulsion was determined against Gram positive GPB (Listeria monocytogenes and Staphylococcus aureus) and Gram negative GNB (Escherichia coli) bacterial strains using minimum inhibitory concentration (MIC) and a time kill dynamic method. Negatively charged PGU emulsified CO nanoemulsion showed prolonged antibacterial activities against Gram positive bacterial strains. We concluded that negatively charged CO nanoemulsion droplets self-assemble with GPB cell membrane, and facilitated interaction with cellular components of bacteria. Moreover, no electrostatic interaction existed between negatively charged droplets and the GPB membrane.

  20. Self-assembly formation of palm-based esters nano-emulsion: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Abdul Rahman, Mohd. Basyaruddin; Huan, Qiu-Yi; Tejo, Bimo A.; Basri, Mahiran; Salleh, Abu Bakar; Rahman, Raja Noor Zaliha Abdul

    2009-10-01

    Palm-oil esters (POEs) are unsaturated and non-ionic esters that can be prepared by enzymatic synthesis from palm oil. Their nano-emulsion properties possess great potential to act as drug carrier for transdermal drug delivery system. A ratio of 75:5:20 (water/POEs/Span20) was chosen from homogenous region in the phase diagram of our previous experimental work to undergo molecular dynamics simulation. A 15 ns molecular dynamics simulation of nano-emulsion system (water/POEs/Span20) was carried out using OPLS-AA force field. The aggregations of the oil and surfactant molecules are observed throughout the simulation. After 8 ns of simulation, the molecules start to aggregate to form one spherical micelle where the POEs molecules are surrounded by the non-ionic surfactant (Span20) molecules with an average size of 4.2 ± 0.05 nm. The size of the micelle and the ability of palm-based nano-emulsion to self-assemble suggest that this nano-emulsion can potentially use in transdermal drug delivery system.

  1. Enhanced Bioavailability of Curcumin Nanoemulsions Stabilized with Phosphatidylcholine Modified with Medium Chain Fatty Acids.

    PubMed

    Ochoa-Flores, Angélica A; Hernández-Becerra, Josafat A; Cavazos-Garduño, Adriana; Soto-Rodríguez, Ida; Sanchez-Otero, Maria Guadalupe; Vernon-Carter, Eduardo J; García, Hugo S

    2017-01-01

    Curcumin is a natural, oil-soluble polyphenolic compound with potent anticancer, anti-inflammatory, and antioxidant activities. In its free form, it is very poorly absorbed in the gut due to its very low solubility. The use of nanoemulsions as carrier is a feasible way for improving curcumin bioavailability. To this end, the choice of emulsifying agent for stabilizing the nanoemulsions is of the upmost importance for achieving a desired functionality. Phosphatidylcholine (PC) and phosphatidycholine enriched (PCE) with medium chain fatty acids (42.5 mol %) in combination with glycerol as co-surfactant, were used for preparing oil-in water nanoemulsions coded as NEPC and NEPCE, respectively. NEPCE displayed significantly smaller mean droplet size (30 nm), equal entrapment efficiency (100%), better droplet stability and suffered lower encapsulation efficiency loss (3%) during storage time (120 days, 4ºC) than NEPC. Bioavailability, measured in terms of area under the curve of curcumin concentration versus time, and maximum curcumin plasma concentration, was in general terms significantly higher for NEPCE than for NEPC, and for curcumin coarse aqueous suspension (CCS). Also, NEPCE produced significantly higher curcumin concentrations in liver and lung than NEPC and CCS. These data support the role of phosphatidylcholine enriched with medium chain fatty acids to increase the bioavailability of nanoemulsions for therapeutic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment.

    PubMed

    Sood, Sumeet; Jain, Kunal; Gowthamarajan, K

    2014-01-01

    The objective of the study was to optimize curcumin nanoemulsion for intranasal delivery using design of experiment. Box-Behnken design was constructed using oil, surfactant and co-surfactant concentration as independent variables and their affect on response y1 (globule size) and y2 (zeta potential) were studied. The ANOVA test identified the significant factors that affected the responses. For globule size, percentage of oil, surfactant and co-surfactant were identified as significant model terms whereas for zeta potential, oil and co-surfactant were found to be significant. Critical factors affecting the responses were identified using perturbation and contour plots. The derived polynomial equation and contour graph aid in predicting the values of selected independent variables for preparation of optimum nanoemulsion with desired properties. Further, 2(4) factorial design was used to study influence of chitosan on particle size and zeta potential. The formulations were subjected to in vitro cytotoxicity using SK-N-SH cell line and nasal ciliotoxicity studies. The developed formulations did not show any toxicity and were safe for intranasal delivery for brain targeting. In vitro diffusion studies revealed that nanoemulsions had a significantly higher release compared to drug solution. Ex vivo diffusion studies were carried out using sheep nasal mucosa fixed onto Franz diffusion cells. Mucoadhesive nanoemulsion showed higher flux and permeation across sheep nasal mucosa.

  3. Thermal conductivity and viscosity of self-assembled alcohol/polyalphaolefin nanoemulsion fluids

    NASA Astrophysics Data System (ADS)

    Xu, Jiajun; Yang, Bao; Hammouda, Boualem

    2011-12-01

    Very large thermal conductivity enhancement had been reported earlier in colloidal suspensions of solid nanoparticles (i.e., nanofluids) and more recently also in oil-in-water emulsions. In this study, nanoemulsions of alcohol and polyalphaolefin (PAO) are spontaneously generated by self-assembly, and their thermal conductivity and viscosity are investigated experimentally. Alcohol and PAO have similar thermal conductivity values, so that the abnormal effects, such as particle Brownian motion, on thermal transport could be deducted in these alcohol/PAO nanoemulsion fluids. Small angle neutron-scattering measurement shows that the alcohol droplets are spheres of 0.8-nm radius in these nanoemulsion fluids. Both thermal conductivity and dynamic viscosity of the fluids are found to increase with alcohol droplet loading, as expected from classical theories. However, the measured conductivity increase is very moderate, e.g., a 2.3% increase for 9 vol%, in these fluids. This suggests that no anomalous enhancement of thermal conductivity is observed in the alcohol/PAO nanoemulsion fluids tested in this study.

  4. Enhancing the antimicrobial activity of d-limonene nanoemulsion with the inclusion of ε-polylysine.

    PubMed

    Zahi, Mohamed Reda; El Hattab, Mohamed; Liang, Hao; Yuan, Qipeng

    2017-04-15

    The objective of this research was to investigate the synergism between ε-polylysine and d-limonene and develop a novel nanoemulsion system by merging the positive effect of these two antimicrobial agents. Results from the checkerboard method showed that ε-polylysine and d-limonene exhibit strong synergistic and useful additive effects against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Saccharomyces cerevisiae. In addition, d-limonene nanoemulsion with the inclusion of ε-polylysine was successfully prepared by high pressure homogenizer technology. Its antimicrobial efficiency was compared with pure d-limonene nanoemulsion by measuring the minimal inhibitory concentration, electronic microscope observation and the leakage of the intercellular constituents. The results demonstrated a wide improvement of the antimicrobial activity of d-limonene nanoemulsion following the inclusion of ε-polylysine. Overall, the current study may have a valuable contribution to make in developing a more efficient antimicrobial system in the food industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Near infrared light absorption in magnetic nanoemulsion under external magnetic field

    NASA Astrophysics Data System (ADS)

    Brojabasi, Surajit; Mahendran, V.; Lahiri, B. B.; Philip, John

    2014-07-01

    We study the magnetic field dependent near infrared photon absorption behavior in a magnetically polarizable oil-in-water emulsion of droplet radius ~110 nm. The absorption of near infrared photons in magnetic nanoemulsion is found to be dependent on the volume fraction and applied magnetic field, which is attributed to the variation in the Mie absorption efficiency during the structural transitions of nanoemulsion droplets in dispersion. Also, the absorption linearly increases with incident near infrared photon energy up to certain external magnetic field. The imaginary part of the refractive index (k1) of magnetic nanoemulsion obtained from the near infrared absorption profile in the Rayleigh regime is found to vary with external magnetic field and the sample volume fraction (ϕ). The measured k1 follows a power law increment with sample volume fraction (k1~ϕ, where p is the exponent). The exponent (p) decreases with external magnetic field implying that the structural transition of nanoemulsion droplets increases k1. After a critical magnetic field (beyond Rayleigh regime), field induced absorption of near infrared photons decreases because of the increase in the aspect ratio of the chain like aggregates and interchain spacing which in turn reduces the Mie absorption efficiency.

  6. Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization.

    PubMed

    Goh, Pik Seah; Ng, Mei Han; Choo, Yuen May; Amru, Nasrulhaq Boyce; Chuah, Cheng Hock

    2015-11-05

    In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%-25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification.

  7. Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation.

    PubMed

    Tang, Siah Ying; Manickam, Sivakumar; Wei, Tan Khang; Nashiru, Billa

    2012-03-01

    In the present study, response surface methodology (RSM) based on central composite design (CCD) was employed to investigate the influence of main emulsion composition variables, namely drug loading, oil content, emulsifier content as well as the effect of the ultrasonic operating parameters such as pre-mixing time, ultrasonic amplitude, and irradiation time on the properties of aspirin-loaded nanoemulsions. The two main emulsion properties studied as response variables were: mean droplet size and polydispersity index. The ultimate goal of the present work was to determine the optimum level of the six independent variables in which an optimal aspirin nanoemulsion with desirable properties could be produced. The response surface analysis results clearly showed that the variability of two responses could be depicted as a linear function of the content of main emulsion compositions and ultrasonic processing variables. In the present investigation, it is evidently shown that ultrasound cavitation is a powerful yet promising approach in the controlled production of aspirin nanoemulsions with smaller average droplet size in a range of 200-300 nm and with a polydispersity index (PDI) of about 0.30. This study proved that the use of low frequency ultrasound is of considerable importance in the controlled production of pharmaceutical nanoemulsions in the drug delivery system. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Antimicrobial eugenol nanoemulsion prepared by gum arabic and lecithin and evaluation of drying technologies.

    PubMed

    Hu, Qiaobin; Gerhard, Hannah; Upadhyaya, Indu; Venkitanarayanan, Kumar; Luo, Yangchao

    2016-06-01

    The purpose of present work was to develop eugenol oil nanoemulsions using gum arabic and lecithin as food grade natural emulsifiers, and study their antimicrobial activity. In addition, our study also evaluated different drying techniques (spray drying and freeze drying) on the morphology and redispersibility of nanoemulsion powders. The optimal fabrication method, physicochemical and structural characterization, stability, and antimicrobial activity were investigated. Results showed that nanoemusions with a particle size of 103.6±7.5nm were obtained by mixing aqueous phase (0.5% gum arabic, 0.5% lecithin, w/v) and eugenol oil (1.25%, w/v), which was premixed with ethanol (as a co-surfactant), followed by high speed homogenization process. The molecular interactions among emulsifiers and eugenol were evidenced by Fourier transform infrared spectroscopy. Buchi B-90 Nano Spray Dryer was evaluated as a powerful tool to obtain ultrafine spherical powders with a size of less than 500nm, compared to flake-like aggregation obtained by freeze-drying. The dried powders exhibited excellent re-dispersibility in water and maintained their physicochemical properties after re-hydration. The nanoemulsions did not adversely affect the antimicrobial activity of eugenol against Listeria monocytogenes and Salmonella Enteritidis. Therefore, the nanoemulsions have the potential to be applied in the food industry as a food preservative or sanitizer. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Characteristics of cinnamaldehyde nanoemulsion prepared using APV-high pressure homogenizer and ultra turrax

    NASA Astrophysics Data System (ADS)

    Asmawati, Mustapha, Wan Aida Wan; Yusop, Salma Mohamad; Maskat, Mohamad Yusof; Shamsuddin, Ahmad Fuad

    2014-09-01

    This work aims at determining the optimized parameter to prepare cinnamaldehyde nanoemulsion by using high pressure homogenizer (2 passes at 900 bar) and ultra turrax T25 (12000 rpm for 5 min). Thirteen formulation of cinnamaldehyde nanoemulsion obtained by Design Expert software were prepared at a range of oil and surfactant concentration between of 5% and 10% (v/v). Commercial cinnamaldehyde was blended with deionized water and Tween 80 (emulsifier). The responses used in obtaining the optimized condition were droplet size, polydispersity index (PDI) and emulsion stability (ζ-potential). Result showed that nanoemulsion prepared using 5% (v/v) cinnamaldehyde and 5% (v/v) Tween 80 and homogenized using high pressure homogenizer (APV, Germany) has the smallest size of droplet. The response surface plots for droplet size showed that droplet size (diameter, nm) decreased as the concentration of cinnamaldehyde oil and Tween 80 decreased. However ζ-potential value (mV) showed an increment as the cinnamaldehyde oil concentration decreased and Tween 80 increased. The optimum formulation as predicted by response surface methodology in order to produce a stable cinnamaldehyde nanoemulsion was at 5% cinnamaldehyde oil and 7.11% Tween 80. At this optimized conditions the droplet size and ζ-potential values were 56.56 nm and -4.32 mV, respectively.

  10. Application of an oregano oil nanoemulsion to the control of foodborne bacteria on fresh lettuce.

    PubMed

    Bhargava, Kanika; Conti, Denise S; da Rocha, Sandro R P; Zhang, Yifan

    2015-05-01

    Although antimicrobial activities of plant essential oils are well documented, challenges remain as to their application in fresh produce due to the hydrophobic nature of essential oils. Oregano oil nanoemulsions were formulated with a food-grade emulsifier and evaluated for their efficacy in inactivating the growth of foodborne bacteria on fresh lettuce. Lettuce was artificially inoculated with Listeria monocytogenes, Salmonella Typhimurium and Escherichia coli O157:H7, followed by a one-minute dipping in oregano oil nanoemulsions (0.05% or 0.1%). Samples were stored at 4 °C and enumerated for bacteria at fixed intervals (0 h, 3 h, 24 h, and 72 h). Compared to control, 0.05% nanoemulsion showed an up to 3.44, 2.31, and 3.05 log CFU/g reductions in L. monocytogenes, S. Typhimurium, and E. coli O157:H7, respectively. Up to 3.57, 3.26, and 3.35 log CFU/g reductions were observed on the same bacteria by the 0.1% treatment. Scanning Electron Microscopy (SEM) demonstrated disrupted bacterial membranes due to the oregano oil treatment. The data suggest that applying oregano oil nanoemulsions to fresh produce may be an effective antimicrobial control strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Physico-chemical characterization of nano-emulsions in cosmetic matrix enriched on omega-3

    PubMed Central

    2011-01-01

    Background Nano-emulsions, as non-equilibrium systems, present characteristics and properties which depend not only on composition but also on their method of preparation. To obtain better penetration, nanocosmeceuticals use nano-sized systems for the delivery of active ingredients to targeted cells. In this work, nano-emulsions composed of miglyol, rapeseed oil and salmon oil were developed as a cosmetic matrix. Measurements of different physico-chemical properties of nano-emulsions were taken according to size, electrophoretic mobility, conductivity, viscosity, turbidity, cristallization and melting point. The RHLB was calculated for each formulation in order to achieve maximum stability. Results Both tween 80 and soya lecithin were found to stabilize formulations. The results showed that rapeseed oil and miglyol are the predominant parameters for determining the expression of results concerning the characterization of emulsion. Based on the mixture design, we achieved the optimal point using the following formulation: 56.5% rapessed oil, 35.5% miglyol, and 8% salmon oil. We considered this formulation to be the best as a nanocosmeceutical product due to the small size, good turbidity, and average HLB. Conclusions This study demonstrates the influence of formulation on the physico-chemical properties of each nano-emulsion obtained by the mixture design. PMID:21936893

  12. Ultrathin cellulose nanosheet membranes for superfast separation of oil-in-water nanoemulsions

    NASA Astrophysics Data System (ADS)

    Zhou, Ke; Zhang, Qiu Gen; Li, Hong Mei; Guo, Nan Nan; Zhu, Ai Mei; Liu, Qing Lin

    2014-08-01

    Oily wastewater is generated in diverse industrial processes, and its treatment has become crucial due to increasing environmental concerns. Herein, novel ultrathin nanoporous membranes of cellulose nanosheets have been fabricated for separation of oil-in-water nanoemulsions. The fabrication approach is facile and environmentally friendly, in which cellulose nanosheets are prepared by freeze-extraction of a very dilute cellulose solution. The as-prepared membranes have a cellulose nanosheet layer with a cut-off of 10-12 nm and a controllable thickness of 80-220 nm. They allow ultrafast water permeation and exhibit excellent size-selective separation properties. A 112 nm-thick membrane has a water flux of 1620 l m-2 h-1 bar-1 and a ferritin rejection of 92.5%. These membranes have been applied to remove oil from its aqueous nanoemulsions successfully, and they show an ultrafast and effective separation of oil-in-water nanoemulsions. The newly developed ultrathin cellulose membranes have a wide application in oily wastewater treatment, separation and purification of nanomaterials.Oily wastewater is generated in diverse industrial processes, and its treatment has become crucial due to increasing environmental concerns. Herein, novel ultrathin nanoporous membranes of cellulose nanosheets have been fabricated for separation of oil-in-water nanoemulsions. The fabrication approach is facile and environmentally friendly, in which cellulose nanosheets are prepared by freeze-extraction of a very dilute cellulose solution. The as-prepared membranes have a cellulose nanosheet layer with a cut-off of 10-12 nm and a controllable thickness of 80-220 nm. They allow ultrafast water permeation and exhibit excellent size-selective separation properties. A 112 nm-thick membrane has a water flux of 1620 l m-2 h-1 bar-1 and a ferritin rejection of 92.5%. These membranes have been applied to remove oil from its aqueous nanoemulsions successfully, and they show an ultrafast and effective

  13. Eugenol oil nanoemulsion: antifungal activity against Fusarium oxysporum f. sp. vasinfectum and phytotoxicity on cottonseeds

    NASA Astrophysics Data System (ADS)

    Abd-Elsalam, Kamel A.; Khokhlov, Alexei R.

    2015-02-01

    The current research deals with the formulation and characterization of bio-based oil-in-water nanoemulsion. The formulated eugenol oil nanoemulsion was characterized by dynamic light scattering, stability test, transmission electron microscopy and thin layer chromatography. The nanoemulsion droplets were found to have a Z-average diameter of 80 nm and TEM study reveals the spherical shape of eugenol oil nanoemulsion (EON). The size of the nanoemulsion was found to be physically stable up to more than 1-month when it was kept at room temperature (25 °C). The TEM micrograph showed that the EON was spherical in shape and moderately mono or di-dispersed and was in the range of 50-110 nm. Three concentrations of the nanoformulation were used to evalute the anti-fusarium activity both in vitro and in vivo experiments. SDS-PAGE results of total protein from the Fusarium oxysporum f. sp. vasinfectum (FOV) isolate before and after treatment with eugenol oil nanoemulsion indicate that the content of extra cellular soluble small molecular proteins decreased significantly in EON-treated fungus. Light micrographs of mycelia and spores treated with EON showed the disruption of the fungal structures. The analysis of variance (ANOVA) for Fusarium wilt incidence indicated highly significant ( p = 0.000) effects of concentration, genotype, and their interaction. The difference in wilt incidence between concentrations and control was not the same for each genotype, that is, the genotypes responded differently to concentrations. Effects of three EON concentration on germination percentage, and radicle length, were determined in the laboratory. One very interesting finding in the current study is that cotton genotypes was the most important factors in determining wilt incidence as it accounted for 93.18 % of the explained (model) variation. In vitro experiments were conducted to evaluate the potential phytotoxic effect of three EON concentrations. Concentration, genotype and

  14. Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells.

    PubMed

    Mota Ferreira, Luana; Gehrcke, Mailine; Ferrari Cervi, Verônica; Eliete Rodrigues Bitencourt, Paula; Ferreira da Silveira, Elita; Hofstatter Azambuja, Juliana; Prates Ramos, Andiara; Nascimento, Kátia; Beatriz Moretto, Maria; Braganhol, Elizandra; Rorato Sagrillo, Michele; Cruz, Letícia

    2016-12-01

    Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment. The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.

  15. Real-time sono-photoacoustic imaging of gold nanoemulsions

    NASA Astrophysics Data System (ADS)

    Arnal, Bastien; Wei, Chen-Wei; Perez, Camilo; Lombardo, Michael; Pelivanov, Ivan M.; Pozzo, Danilo; O'Donnell, Matthew

    2015-03-01

    Phase transition contrast agents were first introduced in ultrasound (US) in the form of perfluorocarbon droplets. When their size is reduced to the nanoscale, surface tension dominates their stability and high pressure is required to vaporize them using long US emissions at high frequencies. Our group recently showed that nanoemulsion beads (100-300 nm) coated with gold nanopsheres could be used as non-linear contrast agents. Beads can be vaporized with light only, inducing stronger photoacoustic signals by increasing thermal expansion. A photoacoustic cavitation threshold study (US: 1.2 MHz, Laser 750 nm and 10-ns pulse) shows that the vaporization thresholds of NEB-GNS can be greatly reduced using simultaneous light and US excitations. The resulting signal is driven only by the pressure amplitude for a fluence higher than 2.4 mJ/cm2. At diagnostic exposures, it is possible to capture very high signals from the vaporized beads at concentrations reduced to 10 pM with optical absorption smaller than 0.01 cm-1. A real-time imaging mode selectively isolating vaporization signals was implemented on a Verasonics system. A linear US probe (L74, 3 MHz) launched short US bursts before light was emitted from the laser. Vaporization of NEB-GNS resulted in a persistent 30-dB signal enhancement compared to a dye with the same absorption. Specific vaporization signals were retrieved in phantom experiments with US scatterers. This technique, called sonophotoacoustics, has great potential for targeted molecular imaging and therapy using compact nanoprobes with potentially high-penetrability into tissue.

  16. Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization.

    PubMed

    Gogoll, Karsten; Stein, Pamela; Lee, K D; Arnold, Philipp; Peters, Tanja; Schild, Hansjörg; Radsak, Markus; Langguth, Peter

    2016-10-01

    Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene are high pressure homogenized together with the antigen SIINFEKL. Freeze drying was performed to eliminate water and to achieve spreadable properties of the formulation for dermal administration. The influence of the different oil components was assessed regarding in vitro drug permeation in a Franz diffusion cell model using a murine skin setup. In vivo performance in terms of cytotoxic T-cell response was assessed in a C57BL/6 mouse model. Whereas Aldara® cream contains imiquimod in a dissolved state, the SN formulations carry the active in a suspended state. This resulted in a reduction of imiquimod permeation across murine skin from the SN when compared to Aldara® cream. In spite of this permeation rate reduction, each SN induced an in vivo immune response by specific T-cell lysis. A stabilized solid nanosuspension containing squalene/tocopherol exhibited a significantly higher performance (p⩽0.05) in comparison with Aldara® cream. MCT based SN exerted an in vivo effect comparable to Aldara®. In conclusion, anhydrous highly dispersed vehicles containing imiquimod in a submicron particle size distribution can represent promising formulations for TCI. The choice of the oil component has a strong influence on SN performance, independent of in vitro drug permeation

  17. Pre-Clinical Evaluation of a Novel Nanoemulsion-Based Hepatitis B Mucosal Vaccine

    PubMed Central

    Nigavekar, Shraddha S.; Janczak, Katarzyna W.; Knowlton, Jessica; Scott, Alison J.; Mank, Nicholas; Cao, Zhengyi; Rathinavelu, Sivaprakash; Beer, Michael R.; Wilkinson, J. Erby; Blanco, Luz P.; Landers, Jeffrey J.; Baker, James R.

    2008-01-01

    Background Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations. Methodology and Principal Findings Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/−17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached ≥106 titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-γ and TNF-α cytokine production and elevated levels of IgG2 subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4°C, 6 months at 25°C and 6 weeks at 40°C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models. Conclusions Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long

  18. Development of sucrose stearate-based nanoemulsions and optimisation through γ-cyclodextrin.

    PubMed

    Klang, Victoria; Matsko, Nadejda; Raupach, Karoline; El-Hagin, Nivine; Valenta, Claudia

    2011-09-01

    Nanoemulsions aimed at dermal drug delivery are usually stabilised by natural lecithins. However, lecithin has a high tendency towards self-aggregation and is prone to chemical degradation. Therefore, the aim of this study was to develop nanoemulsions with improved structure and long-term stability by employing a natural sucrose ester mixture as sole surfactant. A thorough comparison between the novel sucrose stearate-based nanoemulsions and corresponding lecithin-based nanoemulsions revealed that the sucrose ester is superior in terms of emulsifying efficiency, droplet formation as well as physical and chemical stability. The novel formulations exhibited a remarkably homogeneous structure in cryo TEM investigations, as opposed to the variable structure observed for lecithin-based systems. The in vitro skin permeation rates of lipophilic drugs from sucrose stearate nanoemulsions were comparable to those obtained with their lecithin-based counterparts. Furthermore, it was observed that addition of γ-cyclodextrin led to enhanced skin permeation of the steroidal drug fludrocortisone acetate from 9.99±0.46 to 55.10±3.67 μg cm(-2) after 24 h in the case of sucrose stearate-based systems and from 9.98±0.64 to 98.62±24.89 μg cm(-2) after 24 h in the case of lecithin-based systems. This enhancement effect was significantly stronger in formulations based on lecithin (P<0.05), which indicates that synergistic mechanisms between the surfactant and the cyclodextrin are involved. Cryo TEM images suggest that the cyclodextrin is incorporated into the interfacial film, which might alter drug release rates and improve the droplet microstructure. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Formulation development and optimization of palm kernel oil esters-based nanoemulsions containing sodium diclofenac

    PubMed Central

    Rezaee, Malahat; Basri, Mahiran; Rahman, Raja Noor Zaliha Raja Abdul; Salleh, Abu Bakar; Chaibakhsh, Naz; Karjiban, Roghayeh Abedi

    2014-01-01

    Response surface methodology was employed to study the effect of formulation composition variables, water content (60%–80%, w/w) and oil and surfactant (O/S) ratio (0.17–1.33), as well as high-shear emulsification conditions, mixing rate (300–3,000 rpm) and mixing time (5–30 minutes) on the properties of sodium diclofenac-loaded palm kernel oil esters-nanoemulsions. The two response variables were droplet size and viscosity. Optimization of the conditions according to the four variables was performed for preparation of the nanoemulsions with the minimum values of particle size and viscosity. The results showed that the experimental data could be sufficiently fitted into a third-order polynomial model with multiple regression coefficients (R2) of 0.938 and 0.994 for the particle size and viscosity, respectively. Water content, O/S ratio and mixing time, quadrics of all independent variables, interaction between O/S ratio and mixing rate and between mixing time and rate, as well as cubic term of water content had a significant effect (P<0.05) on the particle size of nanoemulsions. The linear effect of all independent variables, quadrics of water content and O/S ratio, interaction of water content and O/S ratio, as well as cubic term of water content and O/S ratio had significant effects (P<0.05) on the viscosity of all nanoemulsions. The optimum conditions for preparation of sodium diclofenac nanoemulsions were predicted to be: 71.36% water content; 0.69 O/S ratio; 950 rpm mixing rate, and 5 minute mixing time. The optimized formulation showed good storage stability in different temperatures. PMID:24531324

  20. Optimization of homogenization-evaporation process for lycopene nanoemulsion production and its beverage applications.

    PubMed

    Kim, Sang Oh; Ha, Thi Van Anh; Choi, Young Jin; Ko, Sanghoon

    2014-08-01

    Lycopene is a natural antioxidant which has several health benefits. Undesirable oxidation of lycopene compromises its health benefits and also affects the sensory quality of food products containing lycopene. Health benefits associated with lycopene in food preparations can be enhanced by preventing its degradation by incorporating it into the oil phase of an oil-in-water nanoemulsion. In this study, lycopene nanoemulsions were prepared from a low-concentration lycopene extract using an emulsification-evaporation technique. The effects of the concentrations of the lycopene extract (0.015 to 0.085 mg/mL) and emulsifier (0.3 to 0.7 mg/mL), and the number of homogenization cycles (2 to 4) on the droplet size, emulsification efficiency (EE), and nanoemulsion stability were investigated and optimized by statistical analysis using a Box-Behnken design. Regression analysis was used to determine the 2nd-order polynomial model relationship of independent and dependent variables, with multiple regression coefficients (R(2)) of 0.924, 0.933, and 0.872, for the droplet size, EE, and nanoemulsion stability, respectively. Analysis of variance showed that the lycopene extract concentration has the most significant effect on all the response variables. Response surface methodology predicted that a formulation containing 0.085 mg/mL of lycopene extract and 0.7 mg/mL of emulsifier, subjected to 3 homogenization cycles, is optimal for achieving the smallest droplet size, greatest emulsion stability, and acceptable EE. The observed responses were in agreement with the predicted values of the optimized formulation. This study provided important information about the statistical design of lycopene nanoemulsion preparation.

  1. Antimicrobial and antibiofilm activities of nanoemulsions containing Eucalyptus globulus oil against Pseudomonas aeruginosa and Candida spp.

    PubMed

    Quatrin, Priscilla Maciel; Verdi, Camila Marina; Ebling de Souza, Márcia; Nunes de Godoi, Samantha; Klein, Bruna; Gundel, Andre; Wagner, Roger; de Almeida Vaucher, Rodrigo; Ourique, Aline Ferreira; Vianna Santos, Roberto Christ

    2017-09-29

    Candida species are the main responsible microorganisms for causing fungal infections worldwide, and Candida albicans is most frequently associated with infectious processes. Pseudomonas aeruginosa is a gram-negative bacterium commonly found in immunocompromised patients. The infection persistence caused by these microorganisms is often related to antimicrobial resistance and biofilm formation. In this context, the objective of the present study was to prepare and characterize nanoemulsions containing Eucalyptus globulus oil and to verify its antimicrobial and antibiofilm activities against P. aeruginosa and Candida spp. The nanoemulsions had a size of approximately 76 nm, a polydispersity index of 0.22, a zeta potential of - 9,42 mV and a pH of approximately 5.0. The E. globulus oil was characterized by gas chromatography, being possible to observe its main components, such as 1-8-Cineol (75.8%), p- Cymene (7.5%), α-Pinene (7.4%) and Limonene (6.4%). The antimicrobial activity of the nanoemulsion was determined from the macrodilution tests and the cell viability curve, where the minimum fungicidal concentration of 0.7 mg/mL for C. albicans and 1.4 mg/mL for C. tropicalis and C. glabrata were obtained. However, the nanoemulsions did not present antimicrobial activity against P. aeruginosa, since it contains only 5% of the oil, being ineffective for this microorganism. The nanoencapsulated oil action against the formed biofilm was evaluated by atomic force microscopy and calcofluor staining, and the nanoemulsion was more efficient for two of the three Candida species when compared to free oil. Copyright © 2017. Published by Elsevier Ltd.

  2. Hyperosmotic nanoemulsions: Development and application of a new antimicrobial treatment for wound care

    NASA Astrophysics Data System (ADS)

    Connell, Sean

    Wound healing is the intricate process that restores function to damaged skin. The process consists of the inflammatory, proliferative and remodeling phases that orchestrate dynamic cellular responses to regenerate the cutaneous barrier. However, microbial contamination of the wound site stimulates a deleterious inflammatory response with the production of endotoxins, exotoxins and proteases that result in secondary injury. The end result is delayed healing, protracted debilitation and increased health care costs. Controlling contamination is critical for proper wound management and reduced burden on the healthcare system. Based on this concern, we developed and applied a new antimicrobial therapeutic that relies on hyperosmotic nanoemulsions (HNE). The biomechanical process consists of a high-energy nanoemulsion component that permeates the protective microbial membrane and a (ii) nonionic hyperosmoticum that facilitates intracellular water extraction to critically dehydrate the pathogen. HNE was shown to be effective against a multitude of pathogens including bacteria, antibiotic-resistant variants, fungi and viruses. Reported non-clinical studies demonstrate that the membrane disrupting nanoemulsion and hyperosmotic component act synergistically to enhance microbicidal activity. Further, results illustrate that pathogen inactivation was rapid as determined by ion and macromolecule leakage assays. Application of HNE in a pre-clinical animal model of wound healing demonstrated the treatment actively promoted healing to reduce treatment times. HNE mitigated wound infection to reduce the inflammatory response and mechanically debrided the wound to facilitate wound closure. Recent work further enhanced the stability of the nanoemulsion component with the addition of surfactant stabilizers using a low-energy spontaneous emulsification process. The refined nanoemulsion composition was stable against physical stressors and long-term storage without disrupting the

  3. Encapsulation of ω-3 fatty acids in nanoemulsion-based delivery systems fabricated from natural emulsifiers: Sunflower phospholipids.

    PubMed

    Komaiko, Jennifer; Sastrosubroto, Ashtri; McClements, David Julian

    2016-07-15

    Nanoemulsions have considerable potential for encapsulating and delivering ω-3 fatty acids, but they are typically fabricated from synthetic surfactants. This study shows that fish oil-in-water nanoemulsions can be formed from sunflower phospholipids, which have advantages for food applications because they have low allergenicity and do not come from genetically modified organisms. Nanoemulsions containing small droplets (d<150 nm) could be produced using microfluidization, by optimizing phospholipid type and concentration, with the smallest droplets being formed at high phosphatidylcholine levels and at surfactant-to-oil ratios exceeding unity. The physical stability of the nanoemulsions was mainly attributed to electrostatic repulsion, with droplet aggregation occurring at low pH values (low charge magnitude) and at high ionic strengths (electrostatic screening). These results suggest that sunflower phospholipids may be a viable natural emulsifier to deliver ω-3 fatty acids into food and beverage products.

  4. An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: a study in a rabbit graft model.

    PubMed

    Lourenço-Filho, Domingos D; Maranhão, Raul C; Méndez-Contreras, Carlos A; Tavares, Elaine R; Freitas, Fatima R; Stolf, Noedir A

    2011-06-01

    In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg · kg(-1) · d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. Copyright © 2011. Published by Mosby, Inc.

  5. Intentions vs. resemblance: understanding pictures in typical development and autism.

    PubMed

    Hartley, Calum; Allen, Melissa L

    2014-04-01

    Research has debated whether children reflect on artists' intentions when comprehending pictures, or instead derive meaning entirely from resemblance. We explore these hypotheses by comparing how typically developing toddlers and low-functioning children with autism (a population impaired in intentional reasoning) interpret abstract pictures. In Experiment 1, both groups mapped familiar object names onto abstract pictures, however, they related the same representations to different 3-D referents. Toddlers linked abstract pictures with intended referents they did not resemble, while children with autism mapped picture-referent relations based on resemblance. Experiment 2 showed that toddlers do not rely upon linguistic cues to determine intended referential relations. Experiment 3 confirmed that the responding of children with autism was not due to perseveration or associative word learning, and also provided independent evidence of their intention-reading difficulties. We argue that typically developing children derive meaning from the social-communicative intentions underlying pictures when resemblance is an inadequate cue to meaning. By contrast, children with autism do not reflect on artists' intentions and simply relate pictures to whatever they happen to resemble. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

    NASA Astrophysics Data System (ADS)

    Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

    2014-12-01

    Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml-1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

  7. Effect of lentil proteins isolate concentration on the formation, stability and rheological behavior of oil-in-water nanoemulsions.

    PubMed

    Primozic, Maja; Duchek, Akaysha; Nickerson, Michael; Ghosh, Supratim

    2017-12-15

    The formation, stability and rheology of 5wt% oil-in-water nanoemulsions as a function of lentil protein isolate concentration (0.5-5wt%) at pH 3.0 was investigated for 28days. All nanoemulsions, except 1wt% protein, showed bimodal droplet size distribution where the larger diameter peak was ascribed to protein aggregates and entrapped oil droplets. The average droplet size for all nanoemulsions measured from the lower diameter peak ranged from 161 to 357nm, which did not change over 28days. Stable flowable nanoemulsions were formed at 1-2wt% protein concentrations. Nanoemulsions with 3 and 5wt% protein formed strong non-flowable gels which showed a two-step yielding behavior during strain-sweep rheology, indicating gel formation by interconnected clusters of proteins and oil droplets. This study demonstrated that lentil protein has a potential to be utilized as an emulsifier in nanoemulsions, as well as in the formation of emulsion gels at higher protein concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Thermal Degradation and Isomerization of β-Carotene in Oil-in-Water Nanoemulsions Supplemented with Natural Antioxidants.

    PubMed

    Yi, Jiang; Fan, Yuting; Yokoyama, Wallace; Zhang, Yuzhu; Zhao, Liqing

    2016-03-09

    The goal of this study was to see the impact on the retention and isomerization of encapsulated β-carotene (BC) in nanoemulsions fortified with natural antioxidants (α-tocopherol (AT) and l-ascorbic acid (AA)). The physical stability of nanoemulsion, oxidative stability, and isomerization of all-trans-β-carotene (BC) in oil-in-water (O/W) nanoemulsions were determined in the presence or absence of natural antioxidants at 25 and 50 °C at certain intervals of time by high-performance liquid chromatography (HPLC). Sodium caseinate was used as the emulsifier, and corn oil (CO) was more protective than medium-chain triglycerides (MCT) and used for isomerization studies. Mean diameters of control (without antioxidants) and AA- and AT-fortified particles were similar. Mean particle diameter of nanoemulsions increased from 10 to 25 nm at 25 °C and from 40 to 50 nm at 50 °C during 30 days of storage. The isomerization from all-trans-BC to cis-BC isomers was inhibited by antioxidants. The isomerization rates were in the following order: 13-cis-BC > 15-cis-BC > 9-cis-BC. AT had better antioxidant activities than AA in inhibiting BC degradation in O/W nanoemulsions. The results indicated that BC encapsulated in nanoemulsions supplemented with antioxidants could significantly improve BC's chemical stability.

  9. Influence of nonionic branched-chain alkyl glycosides on a model nano-emulsion for drug delivery systems.

    PubMed

    Ahmad, Noraini; Ramsch, Roland; Llinàs, Meritxell; Solans, Conxita; Hashim, Rauzah; Tajuddin, Hairul Anuar

    2014-03-01

    The effect of incorporating new nonionic glycolipid surfactants on the properties of a model water/nonionic surfactant/oil nano-emulsion system was investigated using branched-chain alkyl glycosides: 2-hexyldecyl-β(/α)-D-glucoside (2-HDG) and 2-hexyldecyl-β(/α)-D-maltoside (2-HDM), whose structures are closely related to glycero-glycolipids. Both 2-HDG and 2-HDM have an identical hydrophobic chain (C16), but the former consists a monosaccharide glucose head group, in contrast to the latter which has a disaccharide maltose unit. Consequently, their hydrophilic-lipophilic balance (HLB) is different. The results obtained have shown that these branched-chain alkyl glycosides affect differently the stability of the nano-emulsions. Compared to the model nano-emulsion, the presence of 2-HDG reduces the oil droplet size, whereas 2-HDM modify the properties of the model nano-emulsion system in terms of its droplet size and storage time stability at high temperature. These nano-emulsions have been proven capable of encapsulating ketoprofen, showing a fast release of almost 100% in 24h. Thus, both synthetically prepared branched-chain alkyl glycosides with mono- and disaccharide sugar head groups are suitable as nano-emulsion stabilizing agents and as drug delivery systems in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Formation and stability of oil-in-water nanoemulsions containing rice bran oil: in vitro and in vivo assessments

    PubMed Central

    2011-01-01

    Background Nanoemulsions have practical application in a multitude of commercial areas, such as the chemical, pharmaceutical and cosmetic industries. Cosmetic industries use rice bran oil in sunscreen formulations, anti ageing products and in treatments for skin diseases. The aim of this study was to create rice bran oil nanoemulsions using low energy emulsification methods and to evaluate their physical stability, irritation potential and moisturising activity on volunteers with normal and diseased skin types. Results The nanoemulsion developed by this phase diagram method was composed of 10% rice bran oil, 10% surfactants sorbitan oleate/PEG-30 castor oil, 0.05% antioxidant and 0.50% preservatives formulated in distilled water. The nanoemulsion was stable over the time course of this study. In vitro assays showed that this formulation has a low irritation potential, and when applied to human skin during in vivo studies, the nanoemulsion improved the skin's moisture and maintained normal skin pH values. Conclusion The results of irritation potential studies and in vivo assessments indicate that this nanoemulsion has potential to be a useful tool to treat skin diseases, such as atopic dermatitis and psoriasis. PMID:21952107

  11. Analgesic Efficacy and Safety of DALDA Peptide Analog Delivery to the Brain using Oil-in-Water Nanoemulsion Formulation

    PubMed Central

    Shah, Lipa; Kulkarni, Praveen; Ferris, Craig; Amiji, Mansoor M.

    2014-01-01

    Purpose The main objective of this study was to develop and evaluate therapeutic efficacy and safety following systemic delivery of a peptide analgesic into the CNS using an oil-in-water nanoemulsion system. Methods We have formulated a safe and effective, omega-3 rich polyunsaturated fatty acid containing oil-in-water nanoemulsion formulation, for encapsulating and delivering chemically-modified DALDA, a potent mu-opioid peptide analogue, to the CNS. Another challenge with CNS delivery is the lack of a non-invasive bioanalytical technique to confirm CNS uptake and therapeutic efficacy. Using blood oxygen-level dependent (BOLD) functional magenetic resonance imaging (fMRI), we provide quantitative evidence of nanoemulsion-based delivery and analgesic activity of DALDA analogue in capsaicin-induced awake rat model of pain. Results Nanoemulsion formulation effectively encapsulated the modified analgesic peptide and demonstrated efficacy in the capsaicin- pain induced functional magnetic resonance imaging model in rodents. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects. Conclusions Overall, these results show tremendous opportunity for the development of modified peptide analgesic-encapsulated nanoemulsion formulations for CNS delivery and therapeutic efficacy. PMID:24792826

  12. Analgesic efficacy and safety of DALDA peptide analog delivery to the brain using oil-in-water nanoemulsion formulation.

    PubMed

    Shah, Lipa; Kulkarni, Praveen; Ferris, Craig; Amiji, Mansoor M

    2014-10-01

    The main objective of this study was to develop and evaluate therapeutic efficacy and safety following systemic delivery of a peptide analgesic into the CNS using an oil-in-water nanoemulsion system. We have formulated a safe and effective, omega-3 rich polyunsaturated fatty acid containing oil-in-water nanoemulsion formulation, for encapsulating and delivering chemically-modified DALDA, a potent mu-opioid peptide analogue, to the CNS. One of the challenges with CNS delivery is the lack of a non-invasive bioanalytical technique to confirm CNS uptake and therapeutic efficacy. Using blood oxygen-level dependent (BOLD) functional magenetic resonance imaging (fMRI), we provide quantitative evidence of nanoemulsion-based delivery and analgesic activity of DALDA analogue in capsaicin-induced awake rat model of pain. Nanoemulsion formulation effectively encapsulated the modified analgesic peptide and demonstrated efficacy in the capsaicin- pain induced functional magnetic resonance imaging model in rodents. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects. Overall, these results show tremendous opportunity for the development of modified peptide analgesic-encapsulated nanoemulsion formulations for CNS delivery and therapeutic efficacy.

  13. Association efficiency of three ionic forms of oxytetracycline to cationic and anionic oil-in-water nanoemulsions analyzed by diafiltration.

    PubMed

    Orellana, Sandra L; Torres-Gallegos, Cesar; Araya-Hermosilla, Rodrigo; Oyarzun-Ampuero, Felipe; Moreno-Villoslada, Ignacio

    2015-03-01

    The association efficiency of oxytetracycline (OTC) to pharmaceutical available, ionic oil-in-water nanoemulsions is studied. Theoretical mathematical developments allowed us to differentiate by diafiltration (DF) between thermodynamically and kinetically controlled binding of the drug to the nanoemulsions, and relate these important magnitudes to the association efficiency. The nanoemulsions have been prepared by the solvent displacement technique in the presence of cationic and anionic surfactants. The resulting nanoemulsions were stable at 4°C and 25°C for 60 days, have a size of ∼ 200 nm, showing polydispersity indexes ranging between 0.11 and 0.23, and present zeta potentials ranging between -90 and +60 mV, depending on the charge of the surfactants used. The zeta potential of the nanoemulsions influenced the interaction with OTC, having three ionic forms at different pH, namely, cationic, zwitterionic, and anionic. DF proved to be a powerful tool for the quantification of the drug association efficiency, achieving values up to 84%. Furthermore, this technique allowed obtaining different values of the drug fractions reversibly bound (11%-57%) and irreversibly bound (10%-40%) to the nanoemulsions depending on the surfactants used and pH. These findings may be useful for the development of new drug delivery systems, and as routine assays in academia and pharmaceutical industries.

  14. Formation of vitamin D nanoemulsion-based delivery systems by spontaneous emulsification: factors affecting particle size and stability.

    PubMed

    Guttoff, Marrisa; Saberi, Amir Hossein; McClements, David Julian

    2015-03-15

    Oil-in-water nanoemulsions are particularly suitable for encapsulation of lipophilic nutraceuticals because of their ability to form stable and transparent delivery systems with high oral bioavailability. In this study, the influence of system composition and preparation conditions on the particle size and stability of vitamin D nanoemulsions prepared by spontaneous emulsification (SE) was investigated. SE relies on the formation of small oil droplets when an oil/surfactant mixture is titrated into an aqueous solution. The influence of oil phase composition (vitamin D and MCT), surfactant-to-oil ratio (SOR), surfactant type (Tween 20, 40, 60, 80 and 85), and stirring conditions on the initial particle size of vitamin D nanoemulsions was studied. Nanoemulsions with small droplet diameters (d<200 nm) could be formed using Tween 80 at SOR⩾1 at high stirring speeds (800 rpm). These systems were relatively stable to droplet growth at ambient temperatures (<10% in diameter after 1 month storage), but unstable to heating (T>80°C). The thermal stability of the nanoemulsions could be improved by adding a cosurfactant (sodium dodecyl sulphate (SDS)). The spontaneous emulsification method is simple and inexpensive to carry out and therefore has great potential for forming nanoemulsion-based delivery systems for food, personal care, and pharmaceutical applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Physicochemical properties of whey protein, lactoferrin and Tween 20 stabilised nanoemulsions: Effect of temperature, pH and salt.

    PubMed

    Teo, Anges; Goh, Kelvin K T; Wen, Jingyuan; Oey, Indrawati; Ko, Sanghoon; Kwak, Hae-Soo; Lee, Sung Je

    2016-04-15

    Oil-in-water nanoemulsions were prepared by emulsification and solvent evaporation using whey protein isolate (WPI), lactoferrin and Tween 20 as emulsifiers. Protein-stabilised nanoemulsions showed a decrease in particle size with increasing protein concentration from 0.25% to 1% (w/w) level with Z-average diameter between 70 and 90 nm. However, larger droplets were produced by Tween 20 (120-450 nm) especially at concentration above 0.75% (w/w). The stability of nanoemulsions to temperature (30-90°C), pH (2-10) and ionic strength (0-500 mM NaCl or 0-90 mM CaCl2) was also tested. Tween 20 nanoemulsions were unstable to heat treatment at 90°C for 15 min. WPI-stabilised nanoemulsions exhibited droplet aggregation near the isoelectric point at pH 4.5 and 5 and they were also unstable at salt concentration above 30 mM CaCl2. These results indicated that stable nanoemulsions can be prepared by careful selection of emulsifiers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A hypothesis to explain accuracy of wasp resemblances.

    PubMed

    Boppré, Michael; Vane-Wright, Richard I; Wickler, Wolfgang

    2017-01-01

    Mimicry is one of the oldest concepts in biology, but it still presents many puzzles and continues to be widely debated. Simulation of wasps with a yellow-black abdominal pattern by other insects (commonly called "wasp mimicry") is traditionally considered a case of resemblance of unprofitable by profitable prey causing educated predators to avoid models and mimics to the advantage of both (Figure 1a). However, as wasps themselves are predators of insects, wasp mimicry can also be seen as a case of resemblance to one's own potential antagonist. We here propose an additional hypothesis to Batesian and Müllerian mimicry (both typically involving selection by learning vertebrate predators; cf. Table 1) that reflects another possible scenario for the evolution of multifold and in particular very accurate resemblances to wasps: an innate, visual inhibition of aggression among look-alike wasps, based on their social organization and high abundance. We argue that wasp species resembling each other need not only be Müllerian mutualists and that other insects resembling wasps need not only be Batesian mimics, but an innate ability of wasps to recognize each other during hunting is the driver in the evolution of a distinct kind of masquerade, in which model, mimic, and selecting agent belong to one or several species (Figure  1b). Wasp mimics resemble wasps not (only) to be mistaken by educated predators but rather, or in addition, to escape attack from their wasp models. Within a given ecosystem, there will be selection pressures leading to masquerade driven by wasps and/or to mimicry driven by other predators that have to learn to avoid them. Different pressures by guilds of these two types of selective agents could explain the widely differing fidelity with respect to the models in assemblages of yellow jackets and yellow jacket look-alikes.

  17. Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers - a systematic review of in vitro data.

    PubMed

    Doktorovova, Slavomira; Souto, Eliana B; Silva, Amélia M

    2014-05-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative to other colloidal carriers. They were designed to overcome lipid nanoemulsions and liposomes in stability and ability to control the release of an encapsulated substance, and at the same time to be better tolerated than polymeric nanoparticles. Since the patenting of SLN discovery, large amount of data became available on the behaviour of these systems in vitro. SLN/NLC have many prerequisites to be a well tolerated carrier - the currently available data seem to confirm it, but there are also some contradictory results. In this review, we collected the available data from cytotoxicity, oxidative stress and hemocompatibility studies in vitro and analysed their outcomes. We also provide a summary of the available data in a form of reference table. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion

    PubMed Central

    Rachmawati, Heni; Soraya, Irene Surya; Kurniati, Neng Fisheri; Rahma, Annisa

    2016-01-01

    Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self

  19. Characterization of Stability and Nasal Delivery Systems for Immunization with Nanoemulsion-Based Vaccines

    PubMed Central

    Nigavekar, Shraddha S.; Bielinska, Anna U.; Mank, Nicholas; Shetty, Abhishek M.; Suman, Julie; Knowlton, Jessica; Myc, Andrzej; Rook, Trent; Baker, James R.

    2010-01-01

    Abstract Background Many infectious diseases that cause significant morbidity and mortality, especially in the developing world, could be preventable through vaccination. The effort to produce safe, thermally stable, and needle-free mucosal vaccines has become increasingly important for global health considerations. We have previously demonstrated that a thermally stable nanoemulsion, a mucosal adjuvant for needle-free nasal immunization, is safe and induces protective immunity with a variety of antigens, including recombinant protein. The successful use of nanoemulsion-based vaccines, however, poses numerous challenges. Among the challenges is optimization of the formulation to maintain thermal stability and potency and another is accuracy and efficiency of dispensing the vaccines to the nasal mucosa in the anterior and turbinate region of the nasal cavity or potentially to the nasopharynx-associated lymphoid tissue. Methods We have examined the effects of different diluents [phosphate-buffered saline (PBS) and 0.9% NaCl] on the stability and potency of nanoemulsion-based vaccines. In addition, we have determined the efficiency of delivering them using commercially available nasal spray devices (Pfeiffer SAP-62602 multidose pump and the BD Hypak SCF 0.5 ml unit dose AccusprayTM). Results We report the stability and potency of PBS–diluted ovalbumin–nanomeulsion mixtures for up to 8 months and NaCl-diluted mixtures up to 6 months when stored at room temperature. Significant differences in spray characteristics including droplet size, spray angle, plume width, and ovality ratios were observed between the two pumps. Further, we have demonstrated that the nanoemulsion-based vaccines are not physically or chemically altered and retain potency following actuation with nasal spray devices. Using either device, the measured spray characteristics suggest deposition of nanoemulsion-based vaccines in inductive tissues located in the anterior region of the nasal cavity

  20. In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion.

    PubMed

    Rachmawati, Heni; Soraya, Irene Surya; Kurniati, Neng Fisheri; Rahma, Annisa

    2016-01-01

    Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self

  1. Family resemblance in fat intake in The Netherlands.

    PubMed

    Feunekes, G I; Stafleu, A; de Graaf, C; van Staveren, W A

    1997-12-01

    To assess family resemblance in fat intake in a representative sample of Dutch families. Households (n = 1077) with children between 1 and 30 y old were selected from the data set of the Dutch National Food Consumption Survey 1992. Two-day diet records were available for all household members. Pearson correlation coefficients for fat and fatty acid intakes (En%) ranged from r = 0.51 to r = 0.61 between parents, and from r = 0.52 to r = 0.72 between siblings. The mean associations in fat and fatty acid intake (En%) between mothers or fathers and children ranged from r = 0.37 to r = 0.50, and they were surprisingly similar for children from 1-3 y of age up to children above 21 y of age. Associations were consistently high for foods eaten at home, and weak for foods eaten outside of the home. Similar within-family associations were found in a set of 1052 households of the Dutch National Food Consumption Survey of 1987. Reported adherence to a therapeutic diet by one of the parents did not erase within-family intake correlations, suggesting that family resemblance is a dynamic phenomenon. Dutch parents and children living together resemble each other in short term intake of fats and fatty acids. This study was supported by the Ministry of Agriculture, Nature Management and Fisheries. Fat intake; dietary intake; social environment; family resemblance.

  2. ASL Nominal Constructions Involving Signs That Resemble Pronouns

    ERIC Educational Resources Information Center

    Sloan, Vivion Smith

    2013-01-01

    This dissertation examines six different types of noun phrases that commonly occur in American Sign Language. These noun phrases all include at least a head noun and one of four signs resembling a pronoun. Videos of natural ASL discourses are gathered, multiple instances of the six types of noun phrases are identified, and their meanings are…

  3. Differential grandparental investment - the impact of phenotypic resemblance.

    PubMed

    Schlee, Juliane; Kirchengast, Sylvia

    2015-01-01

    Differential grandparental investment is mainly explained as a result of paternity uncertainty. Phenotypic resemblance may be interpreted as an indicator of genetically relatedness. Consequently the present study focused on the impact of phenotypic resemblance on grandparental investment, i.e. solicitude, contact frequency and quality of relationship. 213 adults persons between the age 19 and 32 years (x = 25.5; SD = 3.4) were enrolled in the study. Data concerning grandparental investment during childhood were collected retrospectively using a 30 item questionnaire. Grandparental investment patterns differed significantly according grandparent category. In detail maternal grandmothers showed the highest contact frequency and the highest solicitude while - as to be expected - the paternal grandfather exhibited the lowest degree of investment. Grandparental investment was independent of grandparent category mainly influenced by residential distance. Phenotypic resemblance had an impact on grandparental investment independent of residential distance. This was first of all true of paternal grandfathers. An impact of phenotypic resemblance on grandparental investment patters can be assumed.

  4. Lipid Profile

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Lipid Profile Share this page: Was this page helpful? Also ... as: Lipid Panel; Coronary Risk Panel Formal name: Lipid Profile Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Triglycerides ; ...

  5. Comparative pharmacokinetics and tissue distribution analysis of systemically administered 17-β-estradiol and its metabolites in vivo delivered using a cationic nanoemulsion or a peptide-modified nanoemulsion system for targeting atherosclerosis.

    PubMed

    Deshpande, Dipti; Kethireddy, Sravani; Gattacceca, Florence; Amiji, Mansoor

    2014-04-28

    The primary objective of this study was to compare the biodistribution and pharmacokinetic profile of 17-β-estradiol (17-βE) on systemic delivery using either the cationic or the CREKA-peptide-modified (Cysteine-Arginine-Glutamic-acid-Lysine-Alanine) omega-3-fatty acid oil containing nanoemulsion system in vivo in the wild type C57BL/6 mice. Higher blood concentrations of 17-βE, higher accumulation in the tissues of interest - heart and aorta, and higher accumulation within the other tissues - liver and kidney was observed on delivering 17-βE using the CREKA-peptide-modified nanoemulsion system (AUClast in plasma - 263.89±21.81min*%/injected dose/ml) as compared to the cationic nanoemulsion (AUClast in plasma - 20.2±1.86min*%/injected dose/ml) and solution form (AUClast in plasma - 44.9±1.24min*%/injected dose/ml) respectively. Both, the cationic nanoemulsion and the CREKA-peptide-modified nanoemulsion showed a higher relative targeting efficiency of 4.57 and 4.86 respectively for 17-βE than the relative targeting efficiency of 1.78 observed with the solution form. In conclusion, since the maximum exposure (highest AUClast for plasma and tissues) for 17-βE was observed with the CREKA-peptide-modified nanoemulsion system, the study shows that CREKA-peptide-modified nanoemulsion system was the most suitable vehicle for systemic delivery of 17-βE in the wild type C57BL/6 mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery.

    PubMed

    Khatak, Sunil; Dureja, Harish

    2015-01-01

    The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs.

  7. The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

    PubMed

    Hussein, Jihan; El-Banna, Mona; Mahmoud, Khaled F; Morsy, Safaa; Abdel Latif, Yasmin; Medhat, Dalia; Refaat, Eman; Farrag, Abdel Razik; El-Daly, Sherien M

    2017-06-01

    The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect

  8. The release and analgesic activities of morphine and its ester prodrug, morphine propionate, formulated by water-in-oil nanoemulsions.

    PubMed

    Wang, Jhi-Joung; Hung, Chi-Feng; Yeh, Chi-Hui; Fang, Jia-You

    2008-05-01

    In this study, we examined the feasibility of water-in-oil (w/o) nanoemulsions as sustained-release systems for morphine, following subcutaneous administration in rats. The ester prodrug of morphine, morphine propionate (MPR), was also utilized in this study. A variety of nanoemulsions were prepared using soybean oil or sesame oil as the external phase. Span 80, Tween 80, Plurol diisostearique and Brij 98 were used as surfactants in the w/o interface. The effects of the formulation variables on the characteristics of the nanoemulsions, such as inner droplet size, zeta potential, viscosity, drug partitioning, drug release and pharmacological effect, were evaluated. Mean sizes of nanoemulsions of 50-200 nm were obtained. The initial surface charge of the emulsions was found to be around - 3 to - 4 mV, except that the Plurol-containing vehicle showed a highly negative charge of - 23 mV. The loading of morphine and MPR into the nanoemulsions resulted in slower sustained-release behavior as compared with the drug/prodrug in aqueous solution. The rate of morphine released across the membrane was found to be highly dependent on the choice of oil and surfactant types. On the other hand, discrepancies in MPR release rates among the various formulations were minimal. The in vivo analgesic duration of morphine by targeting the drug to central nerve system could be prolonged from 1 to 3 h by incorporating the drug into nanoemulsions using Span 80 or Tween 80 as the surfactant. These results suggest that w/o nanoemulsions are well suited to provide sustained morphine delivery for therapeutic purposes.

  9. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability.

    PubMed

    Tan, Suk Fei; Masoumi, Hamid Reza Fard; Karjiban, Roghayeh Abedi; Stanslas, Johnson; Kirby, Brian P; Basri, Mahiran; Basri, Hamidon Bin

    2016-03-01

    Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy. Copyright © 2015 Elsevier B.V. All

  10. Dense Cluster Formation during Aggregation and Gelation of Attractive Slippery Nanoemulsion Droplets

    SciTech Connect

    Wilking, J.N.; Graves, S.M.; Chang, C.B.; Meleson, K.; Mason, T.G.; Lin, M.Y.

    2006-01-13

    Using time-resolved small angle neutron scattering, we have measured the wave-number-dependent structure factor S(q) of monodisperse nanoemulsions that aggregate and gel after we suddenly turn on a strong, short-range, slippery attraction between the droplets. At high q, peaks in S(q) appear as dense clusters of droplets form, and S(q) increases strongly toward low q, as these dense clusters become locked into a rigid gel network, despite the fluidity of the films between the droplets. The long-time high-q structure of nanoemulsion gels formed by slippery diffusion-limited cluster aggregation is universal in shape and remarkably independent of the droplet volume fraction, {phi}.

  11. Isotropic-to-nematic phase transition of liquid crystals confined in nanoemulsion droplets

    NASA Astrophysics Data System (ADS)

    Bono, S.; Takanishi, Y.; Yamamoto, J.

    2015-01-01

    We fabricated liquid crystalline nanoemulsions (LCNEs) by introducing low molecular weight liquid crystals (LMWLCs) into the core of nanoemulsions, and investigated the phase transition behavior of LMWLCs in the core part with the various weight ratios of LMWLCs to surfactants. The polarized dynamic light scattering measurement was performed to estimate the radii of LCNEs, and it is found that their radii can be controlled by the weight ratio of LMLCs to surfactant polymers. In the depolarized light scattering, it was revealed that the order of the isotropic-nematic phase transition behavior changes from the first order to biased second order with decreasing radius of LCNEs because of the three-dimensional confinement effect surrounded by an anchoring surface.

  12. Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Tekade, Rakesh Kumar; Karan, Saumen; Jaisankar, P; Pal, Tapan Kumar

    2016-12-01

    Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy for Leishmania spp.

    NASA Astrophysics Data System (ADS)

    Betzler de Oliveira de Siqueira, Luciana; da Silva Cardoso, Verônica; Almeida Rodrigues, Igor; Lúcia Vazquez-Villa, Ana; Pereira dos Santos, Elisabete; da Costa Leal Ribeiro Guimarães, Bruno; dos Santos Cerqueira Coutinho, Cristal; Vermelho, Alane Beatriz; Ricci Junior, Eduardo

    2017-02-01

    Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic® F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.

  14. Nanoemulsion drug delivery by ketene based polyester synthesized using electron rich carbon/silica composite surface.

    PubMed

    Swarnalatha, S; Selvi, P K; Ganesh Kumar, A; Sekaran, G

    2008-09-01

    A new carrier matrix for nanoemulsion drug delivery was synthesized from glycine as the raw material, using mesoporous/microporous electron rich carbon-silica composite surface (MAC(800)). MAC(800) was prepared from rice husk in two-stage carbonization. The surface area, pore volume, and pore size distribution of MAC(800) were measured, using nitrogen adsorption isotherms at 77K. The unpaired electron density of MAC(800) was measured in electron spin resonance spectroscopy (ESR), using TEMPOL (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) as the reference spin probe. Glycine was converted into ketene at the surface of MAC(800), which further underwent radical polymerization to form a low molecular weight ketene polymer (LMKP) of ester structure. The structure and the properties of LMKP were confirmed through (13)C, (1)H and DEPT nuclear magnetic resonance (NMR) spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and size exclusion chromatography (SEC). The two hydrophilic drugs namely ciprofloxacin hydrochloride (CPH) and gentamicin sulphate (GS) were chosen for the nanoemulsion preparation and characterization. They were characterized for morphology, interaction of drugs with the polymer and their crystallinity, using HR-TEM, DSC and XRD, respectively. The encapsulation efficiency of the LMKP towards the drugs ciprofloxacin hydrochloride and gentamicin sulphate were 26% and 12%, respectively. The dissolution studies of the nanoemulsion were carried out for the pH 6.5, 7.4 and 8.0. The cytocompatibility studies were done for LMKP as well as nanoemulsion using Hep2 epithelial cells.

  15. Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy for Leishmania spp.

    PubMed

    de Oliveira de Siqueira, Luciana Betzler; da Silva Cardoso, Verônica; Rodrigues, Igor Almeida; Vazquez-Villa, Ana Lúcia; Dos Santos, Elisabete Pereira; da Costa Leal Ribeiro Guimarães, Bruno; Dos Santos Cerqueira Coutinho, Cristal; Vermelho, Alane Beatriz; Junior, Eduardo Ricci

    2017-02-10

    Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic(®) F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.

  16. Treatment with a novel topical nanoemulsion (NB-001) speeds time to healing of recurrent cold sores.

    PubMed

    Kircik, Leon; Jones, Terry M; Jarratt, Michael; Flack, Mary R; Ijzerman, Marian; Ciotti, Susan; Sutcliffe, Joyce; Boivin, Guy; Stanberry, Lawrence R; Baker, James R

    2012-08-01

    Current topical therapies for cold sores are only marginally beneficial due to poor skin penetration. We assessed the safety and efficacy of a novel topical antiviral nanoemulsion (NB-001) with high tissue bioavailability. The primary endpoint was the time to lesion healing. 482 subjects with recurrent cold sores were randomized to self-initiate treatment with either vehicle or NB-001 (0.1%, 0.3% or 0.5%) at the first signs or symptoms of a cold sore episode. Lotion was applied 5 times per day, approximately 3 to 4 hours apart, for 4 days. Time to lesion healing was correlated with NB-001 bioavailability determined in human cadaver skin. Subjects treated with 0.3% NB-001 showed a 1.3-day improvement in the mean time to healing compared to vehicle (P=0.006). This was consistent with human cadaver skin data indicating that the 0.3% nanoemulsion had the highest bioavailability, compared to 0.1% and 0.5% emulsions. No significant safety or dermal irritation concerns or systemic absorption were noted with any of the doses. Topical NB-001 (0.3%) was well tolerated and highly efficacious in shortening the time to healing of cold sores. The improvement in time to healing was similar to that reported for oral nucleoside analogues, but without systemic exposure. Topical agents for recurrent herpes labialis (cold sores) reduce healing time by one half day, compared to oral therapies that speed healing by a day or more. A topical antiviral nanoemulsion was well tolerated and improved cold sore healing time by over a day compared to vehicle control. Nanoemulsion (NB-001) could represent a more efficacious topical treatment for recurrent cold sores.

  17. Fabrication of vitamin E-enriched nanoemulsions: factors affecting particle size using spontaneous emulsification.

    PubMed

    Saberi, Amir Hossein; Fang, Yuan; McClements, David Julian

    2013-02-01

    Oil-in-water nanoemulsions are finding increasing use as delivery systems to encapsulate lipophilic bioactive components in functional food, personal care, and pharmaceutical products. We have investigated the influence of system composition and preparation conditions on the particle size of vitamin E acetate (VE)-loaded nanoemulsions prepared by spontaneous emulsification. This method relies on the formation of very fine oil droplets when an oil/surfactant mixture is added to water. The oil-to-emulsion ratio content was kept constant (10 wt.%) while the surfactant-to-emulsion ratio (%SER) was varied (from 2.5 to 10 wt.%). Oil phase composition (vitamin E to medium chain triglyceride ratio) had a major effect on particle size, with the smallest droplets being formed at 8 wt.% VE and 2 wt.% MCT. Surfactant type also had an appreciable impact on particle size, with TWEEN® 80 giving the smallest droplets from a group of food-grade non-ionic surfactants (TWEEN® 20, 40, 60, 80, and 85). Surfactant-to-emulsion ratio also had to be optimized to produce fine droplets, with the smallest droplets being formed at SER=10 wt.%. Particle size could also be reduced by increasing the temperature and stirring speed used when the oil/surfactant mixture was added to water. By optimizing system composition and homogenization conditions we were able to form VE-loaded nanoemulsions with small mean droplet diameters (d<50 nm) and low polydispersity indexes (PDI<0.13). The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems for food, personal care, and pharmaceutical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation.

    PubMed

    Bouchemal, K; Briançon, S; Perrier, E; Fessi, H

    2004-08-06

    Nano-emulsions consist of fine oil-in-water dispersions, having droplets covering the size range of 100-600 nm. In the present work, nano-emulsions were prepared using the spontaneous emulsification mechanism which occurs when an organic phase and an aqueous phase are mixed. The organic phase is an homogeneous solution of oil, lipophilic surfactant and water-miscible solvent, the aqueous phase consists on hydrophilic surfactant and water. An experimental study of nano-emulsion process optimisation based on the required size distribution was performed in relation with the type of oil, surfactant and the water-miscible solvent. The results showed that the composition of the initial organic phase was of great importance for the spontaneous emulsification process, and so, for the physico-chemical properties of the obtained emulsions. First, oil viscosity and HLB surfactants were changed, alpha-tocopherol, the most viscous oil, gave the smallest droplets size (171 +/- 2 nm), HLB required for the resulting oil-in-water emulsion was superior to 8. Second, the effect of water-solvent miscibility on the emulsification process was studied by decreasing acetone proportion in the organic phase. The solvent-acetone proportion leading to a fine nano-emulsion was fixed at 15/85% (v/v) with EtAc-acetone and 30/70% (v/v) with MEK-acetone mixture. To strength the choice of solvents, physical characteristics were compared, in particular, the auto-inflammation temperature and the flash point. This phase of emulsion optimisation represents an important step in the process of polymeric nanocapsules preparation using nanoprecipitation or interfacial polycondensation combined with spontaneous emulsification technique.

  19. Monitoring the Stability of Perfluorocarbon Nanoemulsions by Cryo-TEM Image Analysis and Dynamic Light Scattering

    PubMed Central

    Grapentin, Christoph; Barnert, Sabine; Schubert, Rolf

    2015-01-01

    Perfluorocarbon nanoemulsions (PFC-NE) are disperse systems consisting of nanoscale liquid perfluorocarbon droplets stabilized by an emulsifier, usually phospholipids. Perfluorocarbons are chemically inert and non-toxic substances that are exhaled after in vivo administration. The manufacture of PFC-NE can be done in large scales by means of high pressure homogenization or microfluidization. Originally investigated as oxygen carriers for cases of severe blood loss, their application nowadays is more focused on using them as marker agents in 19F Magnetic Resonance Imaging (19F MRI). 19F is scarce in organisms and thus PFC-NE are a promising tool for highly specific and non-invasive imaging of inflammation via 19F MRI. Neutrophils, monocytes and macrophages phagocytize PFC-NE and subsequently migrate to inflamed tissues. This technique has proven feasibility in numerous disease models in mice, rabbits and mini pigs. The translation to clinical trials in human needs the development of a stable nanoemulsion whose droplet size is well characterized over a long storage time. Usually dynamic light scattering (DLS) is applied as the standard method for determining particle sizes in the nanometer range. Our study uses a second method, analysis of transmission electron microscopy images of cryo-fixed samples (Cryo-TEM), to evaluate stability of PFC-NE in comparison to DLS. Four nanoemulsions of different composition are observed for one year. The results indicate that DLS alone cannot reveal the changes in particle size, but can even mislead to a positive estimation of stability. The combination with Cryo-TEM images gives more insight in the particulate evolution, both techniques supporting one another. The study is one further step in the development of analytical tools for the evaluation of a clinically applicable perfluorooctylbromide nanoemulsion. PMID:26098661

  20. Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions

    PubMed Central

    Sigward, Estelle; Mignet, Nathalie; Rat, Patrice; Dutot, Mélody; Muhamed, Saleh; Guigner, Jean-Michel; Scherman, Daniel; Brossard, Denis; Crauste-Manciet, Sylvie

    2013-01-01

    Three multiple water-in-oil-in-water (W/O/W) nanoemulsions have been designed for potential inclusion of either lipophilic or hydrophilic drugs using a two-step emulsification process exclusively based on low-energy self-emulsification. The W/O primary emulsion was constituted by a blend of oil (medium chain triglyceride), a mixture (7:3) of two surfactants, and a 10% water phase. The surfactants were a mixture of Polysorbate-85/Labrasol®, Polysorbate-85/Cremophor® EL or glycerol/Polysorbate-85. The final W/O/W nanoemulsions were obtained by the addition of water, with a weight ratio nanoemulsion/water of 1:2. The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively. Cytotoxicity was found for formulations including Labrasol and Cremophor EL. The concentration of emulsion inhibiting 50% cell viability (IC50) was determined using the alamarBlue® test, giving after 24 hours of incubation, IC50 = 10.2 mg/mL for the Labrasol formulation and IC50 = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC50 values for surfactants were 0.51 mg/mL for Labrasol and 0.59 mg/mL for Cremophor EL. In both cases, cytotoxicity was due to an apoptotic mechanism, evidenced by chromatin condensation and P2X7 cell death receptor activation. The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability. Moreover, neither chromatin condensation nor P2X7 activation was found between the 10 and 30 mg/mL final concentration of the emulsion. This last formulation would therefore be of major interest for further developments. PMID:23403891

  1. Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules

    PubMed Central

    Asthana, Shalini; Jaiswal, Anil K.; Gupta, Pramod K.; Pawar, Vivek K.; Dube, Anuradha

    2013-01-01

    The accessible treatment options for life-threatening neglected visceral leishmaniasis (VL) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. Here we formulated nanometric amphotericin B (AmB)-encapsulated chitosan nanocapsules (CNC-AmB) using a polymer deposition technique mediated by nanoemulsion template fabrication. CNC-AmB exhibited good steric stability in vitro, where the chitosan content was found to be efficient at preventing destabilization in the presence of protein and Ca2+. A toxicity study on the model cell line J774A and erythrocytes revealed that CNC-AmB was less toxic than commercialized AmB formulations such as Fungizone and AmBisome. The results of in vitro (macrophage-amastigote system; 50% inhibitory concentration [IC50], 0.19 ± 0.04 μg AmB/ml) and in vivo (Leishmania donovani-infected hamsters; 86.1% ± 2.08% parasite inhibition) experiments in conjunction with effective internalization by macrophages illustrated the efficacy of CNC-AmB at augmenting antileishmanial properties. Quantitative mRNA analysis by real-time PCR (RT-PCR) showed that the improved effect was synergized with the upregulation of tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and inducible nitric oxide synthase and with the downregulation of transforming growth factor β (TGF-β), IL-10, and IL-4. These research findings suggest that a cost-effective CNC-AmB immunoadjuvant chemotherapeutic delivery system could be a viable alternative to the current high-cost commercial lipid-based formulations. PMID:23357762

  2. Compared in vivo efficiency of nanoemulsions unloaded and loaded with calixarene and soapy water in the treatment of superficial wounds contaminated by uranium.

    PubMed

    Grivès, Sophie; Phan, Guillaume; Bouvier-Capely, Céline; Suhard, David; Rebière, François; Agarande, Michelle; Fattal, Elias

    2017-04-01

    No emergency decontamination treatment is currently available in the case of radiological skin contamination by uranium compounds. First responders in the workplace or during an industrial nuclear accident must be able to treat internal contamination through skin. For this purpose, a calixarene nanoemulsion was developed for the treatment of intact skin or superficial wounds contaminated by uranium, and the decontamination efficiency of this nanoemulsion was investigated in vitro and ex vivo. The present work addresses the in vivo decontamination efficiency of this nanoemulsion, using a rat model. This efficiency is compared to the radio-decontaminant soapy water currently used in France (Trait rouge(®)) in the workplace. The results showed that both calixarene-loaded nanoemulsion and non-loaded nanoemulsion allowed a significant decontamination efficiency compared to the treatment with soapy water. Early application of the nanoemulsions on contaminated excoriated rat skin allowed decreasing the uranium content by around 85% in femurs, 95% in kidneys and 93% in urines. For skin wounded by microneedles, mimicking wounds by microstings, nanoemulsions allowed approximately a 94% decrease in the uranium retention in kidneys. However, specific chelation of uranium by calixarene molecules within the nanoemulsion was not statistically significant, probably because of the limited calixarene-to-uranium molar ratio in these experiment conditions. Moreover, these studies showed that the soapy water treatment potentiates the transcutaneous passage of uranium, thus making it bioavailable, in particular when the skin is superficially wounded. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice.

    PubMed

    Hagigit, Tal; Abdulrazik, Muhammad; Valamanesh, Faty; Behar-Cohen, Francine; Benita, Simon

    2012-06-10

    The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal neovascularization and retinopathy of prematurity (ROP) mouse models. Application of saline solution or scrambled ODN17 solution on eyes of rats led to the highest extent of corneal neovascularization. The groups treated with blank nanoemulsion or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal neovascularization with no significant difference with the saline and scrambled ODN17 control solution groups, while the groups treated with ODN17 solution or Avastin® (positive ODN17 control) clearly elicited marked significant inhibition in corneal neovascularization confirming the results reported in the literature. The highest significant corneal neovascularization inhibition efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a 34% inhibition of retinal neovascularization when compared to the aqueous-vehicle-injected eyes. A significantly higher inhibition of vitreal neovascularization (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No difference in extent of neovascularization was observed between blank nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The overall results indicate that cationic nanoemulsion can be considered a promising potential ocular delivery system and an effective therapeutic tool of high clinical significance in the prevention and forthcoming treatment of ocular neovascular diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Transdermal delivery of imipramine and doxepin from newly oil-in-water nanoemulsions for an analgesic and anti-allodynic activity: development, characterization and in vivo evaluation.

    PubMed

    Sandig, A Gimeno; Campmany, A C Calpena; Campos, F Fernández; Villena, M J Martín; Naveros, B Clares

    2013-03-01

    Antidepressants have been considered by their analgesic activity in numerous studies, and specifically tricyclic antidepressants to possess the greatest efficacy. Imipramine and doxepin have been reported to exhibit local anaesthetic properties. In order to investigate their cutaneous analgesic effect after topical application a nanoemulsion vehicle was developed. This nanoemulsion is composed of propilenglicol, Transcutol, water, Labrasol, Plurol Oleique, isostearyl isostearate, oleic acid, and d-limonene. The final concentration of imipramine or doxepin in the nanoemulsion system was 3% (w/w). The nanoemulsions were characterized by pH, viscosity, droplet size, polydispersity index and finally, a morphological and structural examination was carried out by using transmission electron microscopy. Furthermore, the present work also reports stability studies on the nanoemulsion formulations to evaluate the integrity of the formulation; these indicate that formulations are stable for a period of three months. Moreover ex vivo studies were performed to evaluate permeation behaviour through human skin and predict plasma concentrations concluding that topically applied imipramine and doxepin loaded nanoemulsions were safe for a local effect. Similarly, the in vivo analgesic and anti-allodynic activity in rats was evaluated being stronger for the doxepin loaded nanoemulsion. This study demonstrated that nanoemulsion containing doxepin could be promising as an alternative analgesic therapy with a potential clinical application.

  5. Facial resemblances between heterosexual, gay, and lesbian couples.

    PubMed

    Abel, Ernest L; Kruger, Michael L

    2011-06-01

    Researchers have noted a physical resemblance (homophily) between human sex partners. To date, these studies and their related interpretations have been based on heterosexual couples. The present study compared physical resemblances between gay, lesbian, and heterosexual couples, using 40 photographs of each from national newspapers, which were rated by 34 men and 56 women (M age = 53 yr., SD = 12.1). Half the photographs were of actual couples and half were randomly mixed within each group. Actual couples were rated as significantly more similar in appearance than random pairings of people. Ratings of similarity were significantly higher (indicating greater perceived homophily) for gay couples than heterosexual couples, while there was no statistically significant difference in similarity ratings between lesbian couples versus gay and heterosexual couples. The results were interpreted in terms of evolutionary and parental imprinting hypotheses.

  6. 3D printing of self-assembling thermoresponsive nanoemulsions into hierarchical mesostructured hydrogels.

    PubMed

    Hsiao, Lilian C; Badruddoza, Abu Zayed Md; Cheng, Li-Chiun; Doyle, Patrick S

    2017-02-07

    Spinodal decomposition and phase transitions have emerged as viable methods to generate a variety of bicontinuous materials. Here, we show that when arrested phase separation is coupled to the time scales involved in three-dimensional (3D) printing processes, hydrogels with multiple length scales spanning nanometers to millimeters can be printed with high fidelity. We use an oil-in-water nanoemulsion-based ink with rheological and photoreactive properties that satisfy the requirements of stereolithographic 3D printing. This ink is thermoresponsive and consists of poly(dimethyl siloxane) droplets suspended in an aqueous phase containing the surfactant sodium dodecyl sulfate and the cross-linker poly(ethylene glycol) dimethacrylate. Control of the hydrogel microstructure can be achieved in the printing process due to the rapid structural recovery of the nanoemulsions after large strain-rate yielding, as well as the shear thinning behavior that allows the ink to conform to the build platform of the printer. Wiper operations are used to ensure even spreading of the yield stress ink on the optical window between successive print steps. Post-processing of the printed samples is used to generate mesoporous hydrogels that serve as size-selective membranes. Our work demonstrates that nanoemulsions, which belong to a class of solution-based materials with flexible functionalities, can be printed into prototypes with complex shapes using a commercially available 3D printer with a few modifications.

  7. Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles

    PubMed Central

    Rapoport, Natalya Y.; Kennedy, Anne M.; Shea, Jill E.; Scaife, Courtney L.; Nam, Kweon-Ho

    2009-01-01

    The paper reports the results of nanotherapy of ovarian, breast, and pancreatic cancerous tumors by paclitaxel-loaded nanoemulsions that convert into microbubbles locally in tumor tissue under the action of tumor-directed therapeutic ultrasound. Tumor accumulation of nanoemulsions was confirmed by ultrasound imaging. Dramatic regression of ovarian, breast, and orthotopic pancreatic tumors was observed in tumor therapy through systemic injections of drug-loaded nanoemulsions combined with therapeutic ultrasound, signifying efficient ultrasound-triggered drug release from tumor-accumulated nanodroplets. The mechanism of drug release in the process of droplet-to-bubble conversion is discussed. No therapeutic effect from the nanodroplet/ultrasound combination was observed without the drug, indicating that therapeutic effect was caused by the ultrasound-enhanced chemotherapeutic action of the tumor-targeted drug, rather than the mechanical or thermal action of ultrasound itself. Tumor recurrence was observed after the completion of the first treatment round; a second treatment round with the same regimen proved less effective, suggesting that drug resistant cells were either developed or selected during the first treatment round. PMID:19477208

  8. Acoustic Droplet Vaporization, Cavitation, and Therapeutic Properties of Copolymer-Stabilized Perfluorocarbon Nanoemulsions

    SciTech Connect

    Nam, Kweon-Ho; Christensen, Douglas A.; Rapoport, Natalya; Kennedy, Anne M.

    2009-04-14

    Acoustic and therapeutic properties of Doxorubicin (DOX) and paclitaxel (PTX)-loaded perfluorocarbon nanoemulsions have been investigated in a mouse model of ovarian cancer. The nanoemulsions were stabilized by two biodegradable amphiphilic block copolymers that differed in the structure of the hydrophobic block. Acoustic droplet vaporization (ADV) and cavitation parameters were measured as a function of ultrasound frequency, pressure, duty cycles, and temperature. The optimal parameters that induced ADV and inertial cavitation of the formed microbubbles were used in vivo in the experiments on the ultrasound-mediated chemotherapy of ovarian cancer. A combination tumor treatment by intravenous injections of drug-loaded perfluoropentane nanoemulsions and tumor-directed 1-MHz ultrasound resulted in a dramatic decrease of ovarian or breast carcinoma tumor volume and sometimes complete tumor resolution. However, tumors often recurred three to six weeks after the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more aggressive and resistant to the repeated therapy than initial tumors suggesting selection for the resistant cells during the first treatment.

  9. Development of O/W nanoemulsions for ophthalmic administration of timolol.

    PubMed

    Gallarate, M; Chirio, D; Bussano, R; Peira, E; Battaglia, L; Baratta, F; Trotta, M

    2013-01-20

    After an initial screening of ingredients and production methods, nanoemulsions for ocular administration of timolol containing the drug as maleate (TM) or as ion-pair with AOT (TM/AOT) were prepared. The physico-chemical characterization of nanoemulsions, regarding mean diameter, pH, zeta potential, osmolarity, viscosity and surface tension, underlined their feasibility to be instilled into the eyes. Single components and emulsions were tested ex vivo on rabbit corneas to evaluate corneal irritation, that was measured according to opacity test. A marked decrease in corneal opacity was observed using the drug formulated in nanoemulsions rather than in aqueous solutions. Drug permeation and accumulation studies were performed on excised rabbit corneas. An increase in drug permeation through and accumulation into the corneas were observed using TM-AOT compared to TM due to an increase of lipophilicity of the drug as ion-pair. The introduction of chitosan (a positive charged mucoadhesive polymer) into emulsions allowed to increase TM permeation probably due to the interaction of chitosan with corneal epithelial cells.

  10. Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: A potential treatment for melanoma.

    PubMed

    Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; Longo, João Paulo Figueiró; Silva, Jaqueline Rodrigues; Fascineli, Maria Luiza; de Souza, Paulo; Faria, Fernando; Degterev, Igor Anatolievich; Rodriguez, Anselmo; Carneiro, Fabiana Pirani; Lucci, Carolina Madeira; Escobar, Patricia; Amorim, Rivadávio Fernandes Batista; Azevedo, Ricardo Bentes

    2017-01-01

    Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy. Copyright © 2016. Published by Elsevier B.V.

  11. In vitro effects of Eucalyptus staigeriana nanoemulsion on Haemonchus contortus and toxicity in rodents.

    PubMed

    Ribeiro, Wesley Lyeverton Correia; Camurça-Vasconcelos, Ana Lourdes Fernandes; Macedo, Iara Tersia Freitas; dos Santos, Jessica Maria Leite; de Araújo-Filho, José Vilemar; Ribeiro, Juliana de Carvalho; Pereira, Vanessa de Abreu; Viana, Daniel de Araújo; de Paula, Haroldo Cesar Beserra; Bevilaqua, Claudia Maria Leal

    2015-09-15

    Strategies for controlling gastrointestinal nematodes have been developed based on the use of numerous alternative methods, including the use of phytotherapy. New formulations of essential oils with anthelmintic activity have been proposed as a means to optimize their biological effects. Thus, the objective of this study was to formulate a nanoemulsion to optimize the nematicide effect of Eucalyptus staigeriana essential oil (EsEO). Initially, physico-chemical analyses were performed to verify the stability of the E. staigeriana nanoemulsion (EsNano). In vitro tests were conducted to evaluate the ovicidal and larvicidal activities of both EsNano and EsEO against Haemonchus contortus, and toxicology tests were then performed on rodents. The EsEO content in the nanoemulsion was 36.4% (v/v), and the mean particle size was 274.3 nm. EsNano and EsEO inhibited larval hatching by 99% and 96.3% at 1 and 2mg/ml concentrations, respectively, and inhibited larval development by 96.3% and 97.3% at 8 mg/ml concentrations. The acute toxicity test revealed that the EsNano and EsEO doses required to kill 50% of the mice (LD50) were 1,603.9 and 3,495.9 mg/ml, respectively. EsNano did not alter the hematological parameters in the rats after treatment.

  12. Statistical Analysis of Optimal Ultrasound Emulsification Parameters in Thistle-Oil Nanoemulsions.

    PubMed

    Miastkowska, Małgorzata A; Banach, Marcin; Pulit-Prociak, Jolanta; Sikora, Elżbieta S; Głogowska, Agata; Zielina, Michał

    2017-01-01

    Thistle oil (INCI: Silybum marianum seed oil) is known as an anti-oxidant, moisturizing and skin regenerating cosmetic raw material. Nanoemulsions are a new form of cosmetic product showing very good user properties (ease of spreading over the skin with no greasy feeling). Moreover, due to their structure, they can also transport both hydrophilic and hydrophobic active substances to the skin. The aim of this work was the preparation and characterization of nanoemulsions, based on thistle oil. The non-ionic surfactants polysorbate 80 (PEG-20 sorbitan monooleate), decyl glucoside, and a polyglyceryl-4 ester blend were applied to stabilize the nanosystems. All formulations were obtained by a high energy method, using an ultrasonic device (Labsonic U, an ultrasound homogenizer). Variations in the emulsification parameters were tested, including surfactants concentration, pre-emulsification time, ultrasound power and sonication time. On the basis of statistical analysis (experimental design, cluster analysis, classification and regression trees) the best emulsification process parameters were determined. In order to verify the results of statistical analysis, once more an experimental study was conducted. The results obtained confirmed that statistical analysis can be a useful method in determining the conditions for obtaining stable nanoemulsions with desired properties. Formulations obtained with the use of Silybum marianum seed oil were characterized by long-term stability, a low polydispersity index, low viscosity and an average droplet size less than 200 nm.

  13. Fabrication of polymeric nanocapsules from curcumin-loaded nanoemulsion templates by self-assembly.

    PubMed

    Abbas, Shabbar; Karangwa, Eric; Bashari, Mohanad; Hayat, Khizar; Hong, Xiao; Sharif, Hafiz Rizwan; Zhang, Xiaoming

    2015-03-01

    In this study, biodegradable polymeric nanocapsules were prepared by sequential deposition of food-grade polyelectrolytes through the self-assembling process onto the oil (medium chain triglycerides) droplets enriched with curcumin (lipophilic bioactive compound). Optimum conditions were used to prepare ultrasound-assisted nanoemulsions stabilized by octenyl-succinic-anhydride (OSA)-modified starch. Negatively charged droplets (-39.4 ± 1.84 mV) of these nanoemulsions, having a diameter of 142.7 ± 0.85 nm were used as templates for the fabrication of nanocapsules. Concentrations of layer-forming cationic (chitosan) and anionic (carboxymethylcellulose) biopolymers were optimized based on the mean droplet/particle diameter (MDD/MPD), polydispersity index (PDI) and net charge on the droplets/capsules. Prepared core-shell structures or nanocapsules, having MPD of 159.85 ± 0.92 nm, were characterized by laser diffraction (DLS), ζ-potential (ZP), atomic force microscopy (AFM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Furthermore, physical stability of curcumin-loaded nanocapsules in suspension was determined and compared at different storage temperatures. This study may provide information regarding the formation of ultrasound-assisted polymeric nanocapsules from the nanoemulsion templates which could be helpful in the development of delivery systems for lipophilic food bioactives. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Buffered nanoemulsion for nose to brain delivery of ziprasidone hydrochloride: preformulation and pharmacodynamic evaluation.

    PubMed

    Bahadur, Shiv; Pathak, Kamla

    2012-11-01

    The study was undertaken to develop buffered nanoemulsion of ziprasidone hydrochloride (fifth generation antipshychotic) and evaluate its potential for efficacious nose to brain delivery drug delivery in animal models. Homogeneous buffered ziprasidone nanoemulsions (BZNE) were prepared by aqueous (phosphate buffer, pH 8.0) titration method using capmul MCM, labrasol and transcutol as oil, surfactant and cosurfactant respectively. The NEs (F1-F7) were characterized for pharmaceutical characteristics (% transmittance, PDI value, Zeta potential, globule size, viscosity and diffusion coefficient) and F6 with mean globule size of 145.24 ± 4.75nm (PDI = 0.186 ± 0.40) and diffusion coefficient of 0.1901± 0.04cm2/min was thermodynamically stable and was developed as buffered mucoadhesive nanoemulsions. The buffered mucoadhesive NE (βmax = 0.57) that contained 0.5% by weight of chitosan (BZMNE) exhibited 1.79 times higher diffusion coefficient (0.3418 ± 0.03) than BZNE. Pharmacodynamic study confirmed the superiority of BZMNE over BZNE in locomotor activity test (p < 0.05) and paw test (p < 0.05). Nasal ciliotoxicity study revealed the optimized BZMNE to be free from acute toxicity. Conclusively, a stable and efficacious buffered mucoadhesive NE of ziprasidone hydrochloride, that can be safely administered by intranasal route was developed.

  15. Process optimization of ultrasound-assisted curcumin nanoemulsions stabilized by OSA-modified starch.

    PubMed

    Abbas, Shabbar; Bashari, Mohanad; Akhtar, Waseem; Li, Wei Wei; Zhang, Xiaoming

    2014-07-01

    This study reports on the process optimization of ultrasound-assisted, food-grade oil-water nanoemulsions stabilized by modified starches. In this work, effects of major emulsification process variables including applied power in terms of power density and sonication time, and formulation parameters, that is, surfactant type and concentration, bioactive concentration and dispersed-phase volume fraction were investigated on the mean droplet diameter, polydispersity index and charge on the emulsion droplets. Emulsifying properties of octenyl succinic anhydride modified starches, that is, Purity Gum 2000, Hi-Cap 100 and Purity Gum Ultra, and the size stability of corresponding emulsion droplets during the 1 month storage period were also investigated. Results revealed that the smallest and more stable nanoemulsion droplets were obtained when coarse emulsions treated at 40% of applied power (power density: 1.36 W/mL) for 7 min, stabilized by 1.5% (w/v) Purity Gum Ultra. Optimum volume fraction of oil (medium chain triglycerides) and the concentration of bioactive compound (curcumin) dispersed were 0.05 and 6 mg/mL oil, respectively. These results indicated that the ultrasound-assisted emulsification could be successfully used for the preparation of starch-stabilized nanoemulsions at lower temperatures (40-45 °C) and reduced energy consumption.

  16. Acoustic Droplet Vaporization, Cavitation, and Therapeutic Properties of Copolymer-Stabilized Perfluorocarbon Nanoemulsions

    NASA Astrophysics Data System (ADS)

    Nam, Kweon-Ho; Christensen, Douglas A.; Kennedy, Anne M.; Rapoport, Natalya

    2009-04-01

    Acoustic and therapeutic properties of Doxorubicin (DOX) and paclitaxel (PTX)-loaded perfluorocarbon nanoemulsions have been investigated in a mouse model of ovarian cancer. The nanoemulsions were stabilized by two biodegradable amphiphilic block copolymers that differed in the structure of the hydrophobic block. Acoustic droplet vaporization (ADV) and cavitation parameters were measured as a function of ultrasound frequency, pressure, duty cycles, and temperature. The optimal parameters that induced ADV and inertial cavitation of the formed microbubbles were used in vivo in the experiments on the ultrasound-mediated chemotherapy of ovarian cancer. A combination tumor treatment by intravenous injections of drug-loaded perfluoropentane nanoemulsions and tumor-directed 1-MHz ultrasound resulted in a dramatic decrease of ovarian or breast carcinoma tumor volume and sometimes complete tumor resolution. However, tumors often recurred three to six weeks after the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more aggressive and resistant to the repeated therapy than initial tumors suggesting selection for the resistant cells during the first treatment.

  17. Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer.

    PubMed

    Zheng, Nannan; Gao, Yanan; Ji, Hongyu; Wu, Linhua; Qi, Xuejing; Liu, Xiaona; Tang, Jingling

    2016-08-01

    The multidrug resistance (MDR), including intrinsic and acquired multidrug resistance, is a major problem in tumor chemotherapy. Here, we proposed a strategy for modulating intrinsic and/or acquired multidrug resistance by altering the levels of Bax and Bcl-2 expression and inhibiting the transport function of P-gp, increasing the intracellular concentration of its substrate anticancer drugs. Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX) were fabricated in this study, and in vitro anticancer efficacy of the nanoemulsion system was evaluated in the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol. The MNEs-PTX exhibited a remarkably enhanced antiproliferation effect on A2780/Taxol cells than free paclitaxel (PTX) (p < 0.01). Compared with that in the Taxol group, MNEs-PTX further decreased mitochondrial potential. Vitamin E derivative-based multifunctional nanoemulsion (MNEs) obviously increased intracellular accumulation of rhodamine 123 (P-gp substrate). Overexpression of Bcl-2 is generally associated with tumor drug resistance, we found that MNEs could reduce Bcl-2 protein level and increase Bax protein level. Taken together, our findings suggest that anticancer drugs associated with MNEs could play a role in the development of MDR in cancers.

  18. Improved absorption and in vivo kinetic characteristics of nanoemulsions containing evodiamine–phospholipid nanocomplex

    PubMed Central

    Hu, Jiangbo; Chen, Dilong; Jiang, Rong; Tan, Qunyou; Zhu, Biyue; Zhang, Jingqing

    2014-01-01

    Purpose The purpose of this study was to assess the improved absorption and in vivo kinetic characteristics of a novel water-in-oil nanoemulsion containing evodiamine–phospholipid nanocomplex (NEEPN) when administered orally. Methods NEEPN was fabricated by loading an evodiamine–phospholipid nanocomplex into a water-in-oil nanoemulsive system. The gastrointestinal absorption of NEEPN was investigated using an in situ perfusion method. The modified in vivo kinetic characteristics of evodiamine (EDA) in NEEPN were also evaluated. Results Compared with EDA or conventional nanoemulsions containing EDA instead of evodiamine–phospholipid complex, NEEPN with its favorable in vivo kinetic characteristics clearly enhanced the gastrointestinal absorption and oral bioavailability of EDA; for example, the relative bioavailability of NEEPN to free EDA was calculated to be 630.35%, and the effective permeability of NEEPN in the colon was 8.64-fold that of EDA. Conclusion NEEPN markedly improved the oral bioavailability of EDA, which was probably due to its increased gastrointestinal absorption. NEEPN also increased efficacy and reduced adverse effects for oral delivery of EDA. Such finding demonstrates great clinical significance as an ideal drug delivery system demands high efficacy and no adverse effects. PMID:25258531

  19. Nonlinear acoustic enhancement in photoacoustic imaging with wideband absorptive nanoemulsion beads

    NASA Astrophysics Data System (ADS)

    Wei, Chen-wei; Lombardo, Michael; Xia, Jinjun; Pelivanov, Ivan; Perez, Camilo; Larson-Smith, Kjersta; Matula, Thomas J.; Pozzo, Danilo; O'Donnell, Matthew

    2014-03-01

    A nanoemulsion contrast agent with a perfluorohexane core and optically absorptive gold nanospheres (GNSs) assembled on the surface, is presented to improve the specificity of photoacoustic (PA) molecular imaging in differentiating targeted cells or aberrant regions from heterogeneous background signals. Compared to distributed GNSs, clustered GNSs at the emulsion oil-water interface produce a red-shifted and broadened absorption spectrum, exhibiting fairly high absorption in the near-infrared region commonly used for deep tissue imaging. Above a certain laser irradiation fluence threshold, a phase transition creating a microbubble in the emulsion core leads to more than 10 times stronger PA signals compared with conventional thermal-expansion-induced PA signals. These signals are also strongly non-linear, as verified by a differential scheme using recorded PA images at different laser fluences. Assuming a linear relation between laser fluence and the PA signal amplitude, differential processing results in nearly perfect suppression of linear sources, but retains a significant residue for the non-linear nanoemulsion with more than 35 dB enhancement. This result demonstrates that contrast specificity can be improved using the nanoemulsion as a targeting agent in PA molecular imaging by suppressing all background signals related to a linear PA response. Furthermore, combined with a system providing simultaneous laser/ultrasound excitation, cavitation-generated bubbles have the potential to be a highly specific contrast agent for ultrasound molecular imaging and harmonic imaging, as well as a targeted means for noninvasive ultrasound-based therapies.

  20. Antibacterial hydroxypropyl methyl cellulose edible films containing nanoemulsions of Thymus daenensis essential oil for food packaging.

    PubMed

    Moghimi, Roya; Aliahmadi, Atousa; Rafati, Hasan

    2017-11-01

    Edible films containing essential oils (EO) as natural antibacterial agents are promising systems for food preservation. In this work, nanoemulsions of Thymus daenensis EO (wild; F1 and cultivated; F2) were loaded in hydroxyl propyl methyl cellulose (HPMC) films and the effect of different parameters (polymer, plasticizer, and EO concentration) on the film properties were analyzed and optimized. Prepared HPMC films were characterized in terms of EO loading, morphology, mechanical properties, and the antibacterial activity. The results of SEM showed uniform incorporation of nanoemulsions into the edible film. Investigation of the mechanical properties of two edible films revealed a plasticizing effect of T. daenensis EO on the films. Also, edible films had noticeable antimicrobial activity against selected microorganisms, i.e. 47.0±2.5mm and 22.6±0.5mm zone of inhibition against S. aureus for films containing F1 and F2, respectively. Incorporation of nanoemulsions into the HPMC films can be used for active food preservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Preparation and Characterization of Controlled-Release Avermectin/Castor Oil-Based Polyurethane Nanoemulsions.

    PubMed

    Zhang, Hong; Qin, He; Li, Lingxiao; Zhou, Xiaoteng; Wang, Wei; Kan, Chengyou

    2017-06-12

    Avermectin (AVM) is a low-toxic and high-active biopesticide, but it can be easily degraded by UV light. In this paper, biodegradable castor oil-based polyurethanes (CO-PU) are synthesized and used as carriers to fabricate a new kind of AVM/CO-PU nanoemulsion through an emulsion solvent evaporation method, and the chemical structure, colloidal property, AVM loading capacity, controlled-release behavior, foliar adhesion, and photostability of the AVM/CO-PU drug delivery systems are investigated. Results show that AVM is physically encapsulated in the CO-PU carrier nanospheres, the diameter of the AVM/CO-PU nanoparticles is <50 nm, and the AVM/CO-PU films are flat and smooth without any AVM aggregate. The drug loading capacity is up to 42.3 wt % with a high encapsulation efficiency of >85%. The release profiles indicate that the release rate is relatively high at the early stage and then slows, which can be adjusted by loaded AVM content, temperature, and pH of the release medium. The foliar pesticide retention of the AVM/CO-PU nanoemulsions is improved, and the photolysis rate of AVM in the AVM/CO-PU nanoparticles is significantly slower than that of the free AVM. A release mechanism of the AVM/CO-PU nanoemulsions is proposed, which is controlled by both diffusion and matrix erosion.

  2. Castor oil and mineral oil nanoemulsion: development and compatibility with a soft contact lens.

    PubMed

    Katzer, Tatiele; Chaves, Paula; Bernardi, Andressa; Pohlmann, Adriana R; Guterres, Silvia S; Beck, Ruy C R

    2014-03-01

    The non-invasive ophthalmic therapy has a drawback: low residence time in the eye socket. Nanoparticles and contact lenses have been studied as promising ocular drug delivery systems. To develop a nanoemulsion and evaluate its compatibility with a soft contact lens as a potential strategy for ocular delivery. The formulations were developed by spontaneous emulsification and fully characterized. Two drops of nanoemulsion were instilled on the surface of a commercial contact lens and its transparency was measured using a UV-Vis spectrophotometer. Before and after the instillation of the drops, the morphology (scanning electron microscopy - SEM) and ion permeability of the lenses were analyzed. The formulations had a mean particle size of 234 nm, polydispersity below 0.16, zeta potential of -8.56 ± 3.49 mV, slightly acid pH, viscosity ≈1.2 mPa s(-1) and spherical-shaped particles. Nanoemulsion was non-irritant (hen's egg test-chorioallantoic membrane), which was confirmed by the cytotoxicity studies in the SIRC cell cultures. After instillation, SEM analysis showed nanodroplets inside and on the surface of the lenses, although their transparency remained near 100%. No significant differences were found between lens ion permeability coefficients before and after instillation. Formulations presented appropriate physicochemical characteristics and suitability for ocular application. The contact lens remained transparent and ion-permeable after association with the formulation.

  3. Solid-nanoemulsion preconcentrate for oral delivery of paclitaxel: formulation design, biodistribution, and γ scintigraphy imaging.

    PubMed

    Ahmad, Javed; Mir, Showkat R; Kohli, Kanchan; Chuttani, Krishna; Mishra, Anil K; Panda, A K; Amin, Saima

    2014-01-01

    Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4:1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1:1 w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1:1 w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in γ scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC.

  4. Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging

    PubMed Central

    Kislukhin, Alexander A.; Xu, Hongyan; Adams, Stephen R.; Narsinh, Kazim H.; Tsien, Roger Y.; Ahrens, Eric T.

    2016-01-01

    Fluorine-19 magnetic resonance imaging (19F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metalated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate ('FETRIS') nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the 19F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting 19F MRI detection sensitivity is enhanced by 3-to-5 fold over previously used tracers at 11.7 T, and is predicted to increase by at least 8-fold at clinical field strength of 3 T. PMID:26974409

  5. Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen.

    PubMed

    Abd, Eman; Namjoshi, Sarika; Mohammed, Yousuf H; Roberts, Michael S; Grice, Jeffrey E

    2016-01-01

    We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

  6. Solid-Nanoemulsion Preconcentrate for Oral Delivery of Paclitaxel: Formulation Design, Biodistribution, and γ Scintigraphy Imaging

    PubMed Central

    Ahmad, Javed; Mir, Showkat R.; Kohli, Kanchan; Chuttani, Krishna; Mishra, Anil K.; Panda, A. K.

    2014-01-01

    Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4 : 1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1 : 1 w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1 : 1 w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in γ scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC. PMID:25114933

  7. Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Kislukhin, Alexander A.; Xu, Hongyan; Adams, Stephen R.; Narsinh, Kazim H.; Tsien, Roger Y.; Ahrens, Eric T.

    2016-06-01

    Fluorine-19 magnetic resonance imaging (19F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metallated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate (`FETRIS’) nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the 19F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting 19F MRI detection sensitivity is enhanced by three- to fivefold over previously used tracers at 11.7 T, and is predicted to increase by at least eightfold at the clinical field strength of 3 T.

  8. Nanoemulsions as an effective medium for encapsulation and stabilization of cholesterol/β-cyclodextrin inclusion complex.

    PubMed

    Kaur, Khushwinder

    2015-10-01

    Inclusion complex formation between β-cyclodextrin (β-CD) and suitable guest molecules such as cholesterol (Ch) has regularly been exploited to design self-assembled structures. In the present study an effective nanoemulsion medium (lecithin/Tween 80/ethyl oleate/water) was selected for solubilizing and stabilizing Ch and Ch/β-CD inclusion complex. Phase solubility, spectroscopic, thermodynamic, Z-average diameter and morphological analyses were conducted. Phase solubility data analysis demonstrated an increase in Ch solubility at low β-CD concentrations (0.01-0.35 mmol L(-1) ). Transmission electron microscopy and Z-average diameter data indicated the spherical nature of the droplets and confirmed the formation of nanoemulsions with an average size of less than 50 nm. The negative value of ΔG obtained during analysis further indicated that the binding was spontaneous in nature. Primarily, this research demonstrates the use of nanoemulsions as a medium in food matrices, instead of water, for hosting Ch in β-CD. © 2014 Society of Chemical Industry.

  9. Intranasal nanoemulsion-based inactivated respiratory syncytial virus vaccines protect against viral challenge in cotton rats.

    PubMed

    O'Konek, Jessica J; Makidon, Paul E; Landers, Jeffrey J; Cao, Zhengyi; Malinczak, Carrie-Anne; Pannu, Jessie; Sun, Jennifer; Bitko, Vira; Ciotti, Susan; Hamouda, Tarek; Wojcinski, Zbigniew W; Lukacs, Nicholas W; Fattom, Ali; Baker, James R

    2015-01-01

    Respiratory Syncytial Virus is a leading cause of bronchiolitis and pneumonia in infants, the elderly and individuals with compromised immune systems. Despite decades of research, there is currently no available vaccine for RSV. Our group has previously demonstrated that intranasal immunization of mice with RSV inactivated by and adjuvanted with W805EC nanoemulsion elicits robust humoral and cellular immune responses, resulting in protection against RSV infection. This protection was achieved without the induction of airway hyper-reactivity or a Th2-skewed immune response. The cotton rat Sigmodon hispidus has been used for years as an excellent small animal model of RSV disease. Thus, we extended these rodent studies to the more permissive cotton rat model. Intranasal immunization of the nanoemulsion-adjuvanted RSV vaccines induced high antibody titers and a robust Th1-skewed cellular response. Importantly, vaccination provided sterilizing cross-protective immunity against a heterologous RSV challenge and did not induce marked or severe histological effects or eosinophilia in the lung after viral challenge. Overall, these data demonstrate that nanoemulsion-formulated whole RSV vaccines are both safe and effective for immunization in multiple animal models.

  10. In vitro characterization and mosquito (Aedes aegypti) repellent activity of essential-oils-loaded nanoemulsions.

    PubMed

    Nuchuchua, Onanong; Sakulku, Usawadee; Uawongyart, Napaporn; Puttipipatkhachorn, Satit; Soottitantawat, Apinan; Ruktanonchai, Uracha

    2009-01-01

    The nanoemulsions composed of citronella oil, hairy basil oil, and vetiver oil with mean droplet sizes ranging from 150 to 220 nm were prepared and investigated both in vitro and in vivo. Larger emulsion droplets (195-220 nm) shifted toward a smaller size (150-160 nm) after high-pressure homogenization and resulted in higher release rate. We proposed that thin films obtained from the nanoemulsions with smaller droplet size would have higher integrity, thus increasing the vaporization of essential oils and subsequently prolonging the mosquito repellant activity. The release rates were fitted with Avrami's equations and n values were in the same range of 0.6 to 1.0, implying that the release of encapsulated limonene was controlled by the diffusion mechanism from the emulsion droplet. By using high-pressure homogenization together with optimum concentrations of 5% (w/w) hairy basil oil, 5% (w/w) vetiver oil (5%), and 10% (w/w) citronella oil could improve physical stability and prolong mosquito protection time to 4.7 h due to the combination of these three essential oils as well as small droplet size of nanoemulsion.

  11. Anti-cariogenic effect of a cetylpyridinium chloride-containing nanoemulsion

    PubMed Central

    Lee, Valerie A.; Karthikeyan, Ramalingam; Rawls, H. Ralph; Amaechi, Bennett T.

    2010-01-01

    Objectives The aim of this pilot study was to investigate the anticaries activity of a nanoemulsion composed of soybean oil, water, Triton X-100 and cetylpyridinium chloride. Methods Tooth blocks (3 mm length × 3 mm width × 2 mm thickness) were cut from smooth surfaces of selected molar teeth using a water-cooled diamond wire saw. The blocks were randomly assigned to three experimental groups, (A) nanoemulsion, (B) 0.12% chlorhexidine gluconate, and (C) no treatment. The formation of dental caries in human tooth enamel was tested using a continuous flow dual-organism (Streptococcus mutans and Lactobacillus casei), biofilm model, which acts as an artificial mouth and simulates the biological and physiological activities observed within the oral environment. Experimental groups A and B were treated with their respective solutions once daily for 30 seconds on each occasion, while group C received no treatment. 10% sucrose was supplied every 6 hours for 6 minutes to simulate meals and pH cycling. The experiment lasted for 5 days, and the tooth blocks were harvested and processed for demineralization assessment using transverse microradiography (TMR). Results For both lesion depth and mineral loss, statistical analysis indicated that Emulsion was significantly lower than Control and Chlorhexidine, and Chlorhexidine was significantly lower than Control. Conclusions We conclude that cetylpyridinium-containing nanoemulsions appear to present a feasible means of preventing the occurrence of early caries. PMID:20600554

  12. Finger flexion resembling focal dystonia in Isaacs' syndrome.

    PubMed

    Jamora, Roland Dominic G; Umapathi, T; Tan, Louis C S

    2006-01-01

    We describe a patient with a 5-month history of gradually progressive painless flexion of the left ring finger associated with cramps in both thighs. She has severe chronic obstructive pulmonary disease and was on salbutamol. Serum anti-voltage-gated potassium channel antibodies was positive. Electromyography showed generalized neuromyotonia and myokymic discharges. The cramps were partially relieved by phenytoin. We would like to highlight that finger flexion resembling dystonia can be a presenting sign of Isaacs' syndrome.

  13. Arteriovenous shunts resembling patent ductus arteriosus in dogs: 3 cases.

    PubMed

    Fujii, Yoko; Aoki, Takuma; Takano, Hiroshi; Ishikawa, Ryokichi; Wakao, Yoshito

    2009-12-01

    Three dogs presented for the evaluation of cardiac murmurs were diagnosed with aberrant arteriovenous shunts. All cases demonstrated the following findings: 1) relatively soft continuous murmur loudest at the left heart base resembling patent ductus arteriosus (PDA); 2) shunt flow signals in the pulmonary artery on echocardiography; and 3) no PDA on selective angiography, but evidence of anomalous shunting vessels from thoracic aorta to pulmonary vasculature. An aberrant arteriovenous shunt should be considered when a continuous murmur of relatively small intensity is heard.

  14. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

    PubMed

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J

    2015-01-01

    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris. © 2015 Wiley Periodicals, Inc.

  15. Design and formulation of nanoemulsions using 2-(poly(hexafluoropropylene oxide)) perfluoropropyl benzene in combination with linear perfluoro(polyethylene glycol dimethyl ether)

    PubMed Central

    Mountain, Gregory A.; Jelier, Benson J.; Bagia, Christina; Friesen, Chadron M.; Janjic, Jelena M.

    2014-01-01

    This is the first report where PFPAE aromatic conjugates and perfluoro(polyethylene glycol dimethyl ether) are combined and formulated as nanoemulsions with droplet size below 100 nm. A perfluoropolyalkylether (PFPAE) aromatic conjugate, 2-(poly(hexafluoropropylene oxide)) perfluoropropyl benzene, was used as fluorophilic-hydrophilic diblock (FLD) aimed at stabilizing perfluoro(polyethylene glycol dimethyl ether) nanoemulsions. Its effects on colloidal behaviors in triphasic (organic/fluorous/aqueous) nanoemulsions were studied. The addition of FLD construct to fluorous phase led to decrease in PFPAE nanoemulsion droplet size to as low as 85 nm. Prepared nanoemulsions showed high colloidal stability. Our results suggest that these materials represent viable novel approach to fluorous colloid systems design with potential for biomedical and synthetic applications. PMID:24976645

  16. Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability.

    PubMed

    Tan, Suk Fei; Kirby, Brian P; Stanslas, Johnson; Basri, Hamidon Bin

    2017-08-15

    This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA). Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain. Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80. Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA. © 2017 Royal Pharmaceutical Society.

  17. Formation and stability of D-limonene organogel-based nanoemulsion prepared by a high-pressure homogenizer.

    PubMed

    Zahi, Mohamed Reda; Wan, Pingyu; Liang, Hao; Yuan, Qipeng

    2014-12-31

    D-limonene organogel-based nanoemulsion was prepared by high-pressure homogenization technology. The organogelator type had a major role on the formation of the formulations, in which stearic acid has given nanoemulsions with the smallest droplet size. The surfactant type and concentration also had an appreciable effect on droplet formation, with Tween 80 giving a mean droplet diameter (d ≈ 112 nm) among a range of non-ionic surfactants (Tween 20, 40, 60, 80, and 85). In addition, high-pressure homogenization conditions played a key role in the nanoemulsion preparation. The stability of d-limonene organogel-based nanoemulsion was also investigated under two different temperatures (4 and 28 °C) through 2 weeks of storage. Results showed a good stability of the formulations, which is maybe due to the incorporation of D-limonene into the organogel prior to homogenization. This study may have a valuable contribution for the design and use of organogel-based nanoemulsion as a delivery system in food.

  18. A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract.

    PubMed

    Ge, Liang; He, Xinyi; Zhang, Yajie; Zhang, Yuan; Chai, Fujuan; Jiang, Liqun; Webster, Thomas J; Zheng, Chunli

    2017-08-27

    Dabigatran etexilate (DE) is insoluble at neutral pH values but soluble at low pH values due to protonation, which is the major cause for the poor bioavailability of commercial DE products. Here, we first developed a DE nanoemulsion system and improved dissolution in simulated intestinal fluids by encapsulating DE into an oil phase, but 35.8% of the drug still leaked out. Further, we prepared a DE-phospholipid complex (DE-PC) to enhance lipophilicity and solubility of DE. The resulting DE-PC nanoemulsions significantly (P<0.05) reduced drug leakage and subsequent precipitation. As a result, the relative bioavailability of DE-PC nanoemulsions increased to 147.3% and 606.6% compared to DE nanoemulsions and commercial DE products, respectively. Thus, the presently developed drug-phospholipid complex nanoemulsion system is a promising drug delivery system for improving the oral bioavailability of pH-dependent soluble drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Biodistribution and Toxicity of X-Ray Iodinated Contrast Agent in Nano-emulsions in Function of Their Size.

    PubMed

    Attia, Mohamed F; Anton, Nicolas; Akasov, Roman; Chiper, Manuela; Markvicheva, Elena; Vandamme, Thierry F

    2016-03-01

    This study aimed to investigate the impact of the size of X-ray iodinated contrast agent in nano-emulsions, on their toxicity and fate in vivo. A new compound, triiodobenzoate cholecalciferol, was synthetized, formulated as nano-emulsions, and followed after i.v. administration in mice by X-ray imaging (micro computed tomography). Physicochemical characterization and process optimization allowed identifying a good compromise between X-ray contrasting properties, monodispersity and stability. This also allowed selecting two formulations with different sizes, hydrodynamic diameters of 55 and 100 nm, but exactly the same composition. In vitro experiments were performed on two cell lines, namely hepatocytes (BNL-CL2) and macrophages (RAW264.7). Cell viability studies, cell uptake observations by confocal microscopy, and uptake quantification by fluorimetry, disclosed clear differences between two formulations, as well as between two types of cell lines. After i.v. injection of the two iodinated nano-emulsions in mice, CT scans provided the quantification of the pharmacokinetics and biodistributions. We finally showed that the size in the nano-emulsions has not a real impact on the pharmacokinetics and biodistributions, but has a strong influence on their toxicity, corroborating the in vitro results. This study shows that the size of the nanocarrier significantly matters, likely due to highly different interactions with cells and tissues. Graphical Abstract A study on the effect of the size of cholecciferol nano-emulsions, on their in vivo becoming, through X-ray imaging modality.

  20. Ultrasonic emulsification of eucalyptus oil nanoemulsion: antibacterial activity against Staphylococcus aureus and wound healing activity in Wistar rats.

    PubMed

    Sugumar, Saranya; Ghosh, Vijayalakshmi; Nirmala, M Joyce; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-05-01

    The plant derived essential oil nanoemulsion was prepared using a mixture of components containing eucalyptus oil as organic phase, water as continuous phase, and non ionic surfactant, Tween 80, as emulsifier at a particular proportion of 1:1 v/v%. The ultrasonication was applied for varied processing time from 0 to 30 min to study the effect of time on the formation of nanoemulsion and physical stability of formulation by this method. The transparency and stability of emulsion was enhanced when the sonication time was increased compared to hand blender emulsion. The most stable nanoemulsion was obtained in 30 min sonication having the mean droplet diameter of 3.8 nm. The antibacterial studies of nanoemulsion against Staphylococcus aureus by time kill analysis showed complete loss of viability within 15 min of interaction. Observations from scanning electron microscopy of treated bacterial cells confirmed the membrane damage compared to control bacteria. Furthermore, the wound healing potential and skin irritation activity of the formulated nanoemulsion in Wistar rats, suggested non-irritant and higher wound contraction rate with respect to control and neomycin treated rats. These results proposed that the formulated system could be favourable for topical application in pharmaceutical industries. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Formulation of saponin stabilized nanoemulsion by ultrasonic method and its role to protect the degradation of quercitin from UV light.

    PubMed

    Kaur, Khushwinder; Kumar, Raj; Mehta, S K

    2016-07-01

    The objective of the present study was to prepare quercitin (QT) loaded o/w nanoemulsion using food grade surfactants (saponin and tween 80). The prepared nanoemulsion) was stable up to 30 days. The average particle size of the nanoemulsion was 52 ± 10 nm. The formation of saponin stabilized nanoemulsion was confirmed by transmission electron microscopy. Quercitin (QT) trapped nanoemulsion showed higher stability on exposure to UV light (254 nm) as compared to water/ethanol system. The degradation rate was found to decrease from 9 ± 1%, 11 ± 1% at pH 7.4, 8.0 respectively as compared to 42 ± 2% in water/ethanol system. Attempt was also made to study the interaction of QT with two different bile salts (sodium cholate and sodium taurocholate). The free radical scavenging activity of DPPH quercitin and curcumin was compared in NEm media. The obtained IC50 value of quercitin, curcumin and ascorbic acid are 28.88 ± 1, 45.53 ± 2 and 51.51 ± 2 μM respectively. The values of binding constant for sodium cholate (NaC) and sodium taurocholate (NaTC) are 2.66 × 10(5) and 2.72 × 10(4) M(-1) respectively. Sodium cholate (NaC) was found to show strong interaction towards quercitin (QT) due to more electron density on oxygen atom of carboxylate ion. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    PubMed

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2016-11-23

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol( ®) was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  3. Characteristics of spontaneously formed nanoemulsions in octane/AOT/brine systems.

    PubMed

    Kini, Gautam C; Biswal, Sibani Lisa; Wong, Michael S; Miller, Clarence A

    2012-11-01

    Nanoemulsions were formed spontaneously by diluting water-in-oil (W/O) or brine-in-oil (B/O) microemulsions of a hydrocarbon (octane), anionic surfactant (Aerosol-OT or AOT) and water or NaCl brine in varying levels of excess brine. The water-continuous nanoemulsions were characterized by interfacial tension, dynamic light scattering, electrophoresis, optical microscopy and phase-behavior studies. The mechanism of emulsification was local supersaturation and resulting nucleation of oil during inversion. For nanoemulsions formed at low salinities with Winsor I phase behavior, octane drops grew from initial diameters of 150-250 nm to 480-1000 nm over 24h, depending on salinity. Growth was caused by mass transfer but seemed to approach the asymptotic stage of Ostwald ripening described by the Lifshitz-Slyozov-Wagner (LSW) theory only for dilution with salt-free water. Near the higher cross-over salinity (Winsor III), the nanoemulsions showed much slower growth with droplet size consistently remaining below 200 nm over 24h and reaching 250 nm after 1 week. Birefringence indicated the presence of liquid crystal for these conditions, which could have contributed to the slow growth rate. At even higher salinity levels in the Winsor II domain, W/O/W multiple emulsions having drops greater than 1 μm in diameter were consistently recorded for the first 5-7h, after which size decreased to values below 1 μm. The number and size of internal water droplets in multiple emulsion drops was found to decrease over time, suggesting coalescence of internal droplets with the continuous water phase and mass transfer of water from internal droplets to continuous phase as possible mechanisms of the observed drop shrinkage. Electrophoresis studies showed the nanoemulsions to be highly negatively charged (zeta potentials of -60 mV to -120 mV). The high charge on octane droplets helped assure stability to flocculation and coalescence, thereby allowing mass transfer to control growth in the

  4. Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery

    PubMed Central

    Ledet, Grace; Pamujula, Sarala; Walker, Valencia; Simon, Shana; Graves, Richard; Mandal, Tarun K.

    2013-01-01

    Objective The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system. Materials and methods With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied. Results The optimum homogenization regime was determined to be five passes at 20 000 psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2 nm ± 15.5 nm with a polydispersity index of 0.186 ± 0.026 and viscosity of 14.6 cP ± 1.2 cP. The optimized formulation proved stable for 1 year at 4 °C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44 μg/cm2/h for the nanoemulsion as opposed to 6.10 μg/cm2/h for the emulsifiers. Conclusion A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle. PMID:23600657

  5. Presentation of lipid antigens to T cells.

    PubMed

    Mori, Lucia; De Libero, Gennaro

    2008-04-15

    T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

  6. Ex vivo uranium decontamination efficiency on wounded skin and in vitro skin toxicity of a calixarene-loaded nanoemulsion.

    PubMed

    Grives, Sophie; Phan, Guillaume; Morat, Guillaume; Suhard, David; Rebiere, Francois; Fattal, Elias

    2015-06-01

    The present work aims at studying the decontamination efficacy of a calixarene-loaded nanoemulsion on two ex vivo wounded skin models mimicking superficial stings or cuts contaminated with uranium, and on a third model using excoriation. The decontaminating formulation was compared with the currently used radio-decontaminating soapy water (Trait rouge®) treatment. Moreover, to assess skin damage potentially induced by the undiluted nanoemulsion, in vitro toxicity studies were conducted on an in vitro reconstructed human epidermis, coupled with three different toxicity tests [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, lactate dehydrogenase, and interleukin-1-α]. This work demonstrated not only a significant decontamination activity of the calixarene nanoemulsion on wounded skin, ranging from 92% to 94% of the applied uranium solution according to the ex vivo model used, but also the absence of side effects of this promising treatment.

  7. SN 2013fs now resembles a SN IIP

    NASA Astrophysics Data System (ADS)

    Childress, M.; Scalzo, R.; Yuan, F.; Schmidt, B.; Tucker, B.

    2013-10-01

    Further to ATel #5455, we obtained another 40-minutes spectrum of SN 2013fs (was PSN J23194467+1011045) with WiFeS on 2013 Oct 24. The spectrum now strongly resembles an SN IIP, with clear P-Cygni H-alpha, with no evidence of broadened emission. SNID gives a best match to SN 1999em at phase +7. The previously observed emission from the Oct 08 spectrum which prompted a possible IIn classification was most likely due to the host, however we cannot rule out SN-related emission which has faded since the first epoch.

  8. Sequence of retrovirus provirus resembles that of bacterial transposable elements

    NASA Astrophysics Data System (ADS)

    Shimotohno, Kunitada; Mizutani, Satoshi; Temin, Howard M.

    1980-06-01

    The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified λ phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome.

  9. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate.

    PubMed

    Uner, M; Wissing, S A; Yener, G; Müller, R H

    2005-08-01

    The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.

  10. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    PubMed

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-06

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased

  11. Lipid composition of cyanidium.

    PubMed

    Allen, C F; Good, P; Holton, R W

    1970-11-01

    The major lipids in Cyanidium caldarium Geitler are monogalactosyl diglyceride, digalactosyl diglyceride, plant sulfolipid, lecithin, phosphatidyl glycerol, phosphatidyl inositol, and phosphatidyl ethanolamine. Fatty acid composition varies appreciably among the lipids, but the major ones are palmitic acid, oleic acid, linoleic acid, and moderate amounts of stearic acid. Trace amounts of other acids in the C(14) to C(20) range were also present. Moderate amounts of linolenic acid were found in two strains, but not in a third. The proportion of saturated acid is relatively high in all lipids ranging from about a third in monogalactosyl diglyceride to three-fourths in sulfolipid. This may be a result of the high growth temperature. Lipases forming lysosulfolipid, and lysophosphatidyl glycerol are active in ruptured cells; galactolipid is degraded with loss of both acyl residues. Thus the lipid and fatty acid composition of Cyanidium more closely resembles that of green algae than that of the blue-green algae, although there are differences of possible phylogenetic interest.

  12. Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA [Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel

    PubMed Central

    Sarfaraz Alam, Mohammad; Ali, Mohammad Sajid; Zakir, Foziyah; Alam, Nawazish; Intakhab Alam, Mohammad; Ahmad, Faruque; Siddiqui, Masoom Raza; Ali, Mohammad Daud; Ansari, Mohammad Salahuddin; Ahmad, Sarfaraz; Ali, Maksood

    2016-01-01

    The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel. PMID:27610146

  13. Preliminary studies for the development of intranasal nanoemulsion containing CNS agent: emphasizing the utilization of cut and weigh method.

    PubMed

    Kumar, Amrish; Jain, Sunil Kumar

    2017-05-01

    The selection of excipients and preformulation strategy plays a vital role for the development of nanoemulsion, due to anatomical and physiological challenges posed by nasal cavity. This attempt is focused on the selection and optimization of excipients for the development of a nanoemulsion system for intranasal delivery. Excipients were selected on the basis of solubility of active drug, compatibility interactions and nasal irritancy. Surfactant and co-surfactant combination and their ratio were finalized on the basis of nanoemulsion region obtained from constructed phase diagrams with Capmul MCM as oil phase. A validated cut and weigh method was employed for the optimization of different phase diagrams with respect to nanoemulsion region. The solubility of drug in Capmul MCM, Labrasol, and Transcutol-P was found to be superior with numeric values of 79.50 ± 1.68 mg/ml, 51.10 ± 1.39 mg/ml, and 36.60 ± 0.85 mg/ml, respectively. On the basis of phase diagram analysis, Labrasol and Transcutol-P in 3:1 ratio provides greater nanoemulsion region of 65.28 ± 0.18%. The validation of cut and weigh method revealed that there was no significant statistical difference (P > 0.05) with a %RSD value of 2.38 for intersheet variation. The results of validation studies for cut and weigh method suggests that it can be effectively used as an optimization method for the selection of nanoemulsion composition.

  14. Attenuation of oxidative damage by Coenzyme Q10 loaded nanoemulsion via oral route for the management of Parkinson's disease.

    PubMed

    Baboota, Sanjula; Gupta, Bijay Kumar; Kumar, Shobhit; Kaur, Harleen; Ali, Javed

    2017-08-26

    Coenzyme Q10 (CoQ10) is a well known antioxidant molecule which is used in the treatment of neurodegenerative disorders but due to poor solubility it suffers with the drawback of low oral bioavailability. The aim of present study was to prepare and characterize CoQ10 loaded nanoemulsion to improve the oral bioavailability. Prepared formulation was studied for droplet size, polydispersity index (PDI), percentage transmittance, refractive index, viscosity, zeta potential, surface morphology by transmission electron microscopy (TEM) and in vitro release study. Optimized formulation (A10) showed spherical droplets with mean diameter of 60.00 ± 15 nm, PDI of 0.121 ± 0.053 and zeta potential values of -24.40 ± 0.16 mV. Prepared nanoemulsion exhibited good transmittance (100.50 ± 0.86 %), refractive index (1.41 ± 0.02) and viscosity (30.54 ± 2.86 cP). Various behavioural tests like forced swimming test, locomotor activity test, catalepsy, muscle co-ordination test and akinesia test performed in haloperidol challenged rats and treated with CoQ10 nanoemulsion significantly improved the behavioural activities in comparison to CoQ10 suspension by reducing nigrostriatal dopamine depletion and thereby helping in the treatment of Parkinson's disease. Biochemical estimation data showed that CoQ10 nanoemulsion was helpful in elevating the decreased content of glutathione and reducing the increased content of thiobarbituric acid reactive substances (TBARS). Improved CoQ10 release was obtained with nanoemulsions. Pharmacokinetic studies results revealed that nanoemulsion exhibited 1.81 times enhancement in bioavailability in comparison to CoQ10 suspension.

  15. Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA [Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel.

    PubMed

    Sarfaraz Alam, Mohammad; Ali, Mohammad Sajid; Zakir, Foziyah; Alam, Nawazish; Intakhab Alam, Mohammad; Ahmad, Faruque; Siddiqui, Masoom Raza; Ali, Mohammad Daud; Ansari, Mohammad Salahuddin; Ahmad, Sarfaraz; Ali, Maksood

    2016-01-01

    The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel.

  16. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine.

    PubMed

    Sun, HongWu; Wei, Chao; Liu, BaoShuai; Jing, HaiMing; Feng, Qiang; Tong, YaNan; Yang, Yun; Yang, LiuYang; Zuo, QianFei; Zhang, Yi; Zou, QuanMing; Zeng, Hao

    2015-01-01

    The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA) can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35(®) as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (Ig)G and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a robust generator of an effective intramuscular systemic and nasal mucosal immune response without the need for an additional adjuvant. Thus, the present study serves as a sound scientific foundation for future strategies in the development of this novel nanoemulsion adjuvant vaccine to enhance both the intramuscular systemic and nasal mucosal immune responses.

  17. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine

    PubMed Central

    Sun, HongWu; Wei, Chao; Liu, BaoShuai; Jing, HaiMing; Feng, Qiang; Tong, YaNan; Yang, Yun; Yang, LiuYang; Zuo, QianFei; Zhang, Yi; Zou, QuanMing; Zeng, Hao

    2015-01-01

    The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA) can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35® as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (Ig)G and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a robust generator of an effective intramuscular systemic and nasal mucosal immune response without the need for an additional adjuvant. Thus, the present study serves as a sound scientific foundation for future strategies in the development of this novel nanoemulsion adjuvant vaccine to enhance both the intramuscular systemic and nasal mucosal immune responses. PMID:26664118

  18. Development and validation of an ultraviolet-visible spectrophotometric method for determination of phenylethyl resorcinol in new topical nanoemulsions.

    PubMed

    Hong, L; Han, D; Li, M-X; Zhang, P; Liu, C-G

    2017-06-01

    To develop a rapid, simple and efficient ultraviolet-visible (UV-vis) spectrophotometric method for the quantification of phenylethyl resorcinol (PR), a potent skin-lightening agent, incorporated into new topical nanoemulsions, and to validate this method according to International Commission for Harmonization (ICH) guidelines. UV-vis spectrophotometric method for quantification of PR in new topical nanoemulsions was developed and validated in terms of specificity, linearity, sensitivity, precision and accuracy. The method was applied to determine PR content (extraction recoveries) in the nanoemulsions and entrapment efficiencies. The calibration curve for PR was linear in the range of 10-60 μg mL(-1) , with a determination coefficient (r(2) ) which is higher than 0.999. The limit of detection (LOD) and limit of quantitation (LOQ) were 1.55 and 4.69 μg mL(-1) , respectively. The method was shown to be specific, precise [intraday, interday and reproducibility levels relative standard deviation < 3%] and accurate (between 91.90 ± 1.28% and 104.73 ± 0.60%). The extraction recoveries of PR in nanoemulsions were 97.07%, 96.64% and 103.54% at concentrations of 3, 6 and 9 mg mL(-1) , respectively. The entrapment efficiencies were nearly 100%, which agrees with the oil core location of PR in nanoemulsions. This developed method was confirmed to be rapid, simple, cost-effective, specific, precise, accurate and suitable for determination of PR content in nanoemulsions and entrapment efficiencies. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  19. Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis.

    PubMed

    Kuwabara, Yoshimitsu; Sato, Atsuki; Abe, Hiroko; Abe, Sumino; Kawai, Naoki; Takeshita, Toshiyuki

    2011-01-01

    A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.

  20. Extending disorder: essentialism, family resemblance and secondary sense.

    PubMed

    Pickering, Neil

    2013-05-01

    It is commonly thought that mental disorder is a valid concept only in so far as it is an extension of or continuous with the concept of physical disorder. A valid extension has to meet two criteria: determination and coherence. Essentialists meet these criteria through necessary and sufficient conditions for being a disorder. Two Wittgensteinian alternatives to essentialism are considered and assessed against the two criteria. These are the family resemblance approach and the secondary sense approach. Where the focus is solely on the characteristics or attributes of things, both these approaches seem to fail to meet the criteria for valid extension. However, this focus on attributes is mistaken. The criteria for valid extension are met in the case of family resemblance by the pattern of characteristics associated with a concept, and by the limits of intelligibility of applying a concept. Secondary sense, though it may have some claims to be a good account of the relation between physical and mental disorder, cannot claim to meet the two criteria of valid extension.

  1. Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation.

    PubMed

    Pangeni, Rudra; Choi, Sang Won; Jeon, Ok-Cheol; Byun, Youngro; Park, Jin Woo

    Oxaliplatin (OXA) is a third-generation cisplatin analog that has been approved as first-line chemotherapy in combination with 5-fluorouracil (5-FU) for the treatment of resectable and advanced colorectal cancer. However, the therapeutic efficacy of oral OXA and 5-FU is limited by their low bioavailability due to poor membrane permeability. The aim of the present study was to develop an oral delivery system for OXA and 5-FU. We constructed an ion-pairing complex of OXA with a deoxycholic acid derivative (N(α)-deoxycholyl-l-lysyl-methylester, DCK) (OXA/DCK) as a permeation enhancer. Next, we prepared multiple water-in-oil-in-water nanoemulsions incorporating OXA/DCK and 5-FU to enhance their oral absorption. To evaluate their membrane permeability, we assessed in vitro permeabilities of OXA/DCK and 5-FU through an artificial intestinal membrane and Caco-2 cell monolayer. Finally, oral bioavailability in rats and tumor growth inhibition in the colorectal adenocarcinoma cell (CT26)-bearing mouse model were investigated after oral administration of nanoemulsion containing OXA/DCK and 5-FU. The droplet size of the optimized nanoemulsion was 20.3±0.22 nm with a zeta potential of -4.65±1.68 mV. In vitro permeabilities of OXA/DCK and 5-FU from the nanoemulsion through a Caco-2 cell monolayer were 4.80- and 4.30-fold greater than those of OXA and 5-FU, respectively. The oral absorption of OXA/DCK and 5-FU from the nanoemulsion also increased significantly, and the resulting oral bioavailability values of OXA/DCK and 5-FU in the nanoemulsive system were 9.19- and 1.39-fold higher than those of free OXA and 5-FU, respectively. Furthermore, tumor growth in CT26 tumor-bearing mice given the oral OXA/DCK- and 5-FU-loaded nanoemulsion was maximally inhibited by 73.9%, 48.5%, and 38.1%, compared with tumor volumes in the control group and the oral OXA and 5-FU groups, respectively. These findings demonstrate the therapeutic potential of a nanoemulsion incorporating OXA/DCK and

  2. Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

    PubMed Central

    Pangeni, Rudra; Choi, Sang Won; Jeon, Ok-Cheol; Byun, Youngro; Park, Jin Woo

    2016-01-01

    Oxaliplatin (OXA) is a third-generation cisplatin analog that has been approved as first-line chemotherapy in combination with 5-fluorouracil (5-FU) for the treatment of resectable and advanced colorectal cancer. However, the therapeutic efficacy of oral OXA and 5-FU is limited by their low bioavailability due to poor membrane permeability. The aim of the present study was to develop an oral delivery system for OXA and 5-FU. We constructed an ion-pairing complex of OXA with a deoxycholic acid derivative (Nα-deoxycholyl-l-lysyl-methylester, DCK) (OXA/DCK) as a permeation enhancer. Next, we prepared multiple water-in-oil-in-water nanoemulsions incorporating OXA/DCK and 5-FU to enhance their oral absorption. To evaluate their membrane permeability, we assessed in vitro permeabilities of OXA/DCK and 5-FU through an artificial intestinal membrane and Caco-2 cell monolayer. Finally, oral bioavailability in rats and tumor growth inhibition in the colorectal adenocarcinoma cell (CT26)-bearing mouse model were investigated after oral administration of nanoemulsion containing OXA/DCK and 5-FU. The droplet size of the optimized nanoemulsion was 20.3±0.22 nm with a zeta potential of −4.65±1.68 mV. In vitro permeabilities of OXA/DCK and 5-FU from the nanoemulsion through a Caco-2 cell monolayer were 4.80- and 4.30-fold greater than those of OXA and 5-FU, respectively. The oral absorption of OXA/DCK and 5-FU from the nanoemulsion also increased significantly, and the resulting oral bioavailability values of OXA/DCK and 5-FU in the nanoemulsive system were 9.19- and 1.39-fold higher than those of free OXA and 5-FU, respectively. Furthermore, tumor growth in CT26 tumor-bearing mice given the oral OXA/DCK- and 5-FU-loaded nanoemulsion was maximally inhibited by 73.9%, 48.5%, and 38.1%, compared with tumor volumes in the control group and the oral OXA and 5-FU groups, respectively. These findings demonstrate the therapeutic potential of a nanoemulsion incorporating OXA/DCK and

  3. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson's disease by reducing oxidative stress.

    PubMed

    Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

    2014-12-05

    Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson's disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

  4. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

    PubMed

    Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B

    2010-11-01

    In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  5. Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in rats

    PubMed Central

    He, Wei; Tan, Yanan; Tian, Zhiqiang; Chen, Lingyun; Hu, Fuqiang; Wu, Wei

    2011-01-01

    Nanoemulsions stabilized by traditional emulsifiers raise toxicological concerns for long-term treatment. The present work investigates the potential of food proteins as safer stabilizers for nanoemulsions to deliver hydrophobic drugs. Nanoemulsions stabilized by food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) were prepared by high-pressure homogenization. The toxicity of the nanoemulsions was tested in Caco-2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide viability assay. In vivo absorption in rats was also evaluated. Food protein-stabilized nanoemulsions, with small particle size and good size distribution, exhibited better stability and biocompatibility compared with nanoemulsions stabilized by traditional emulsifiers. Moreover, β-lactoglobulin had a better emulsifying capacity and biocompatibility than the other two food proteins. The pancreatic degradation of the proteins accelerated drug release. It is concluded that an oil/water nanoemulsion system with good biocompatibility can be prepared by using food proteins as emulsifiers, allowing better and more rapid absorption of lipophilic drugs. PMID:21468355

  6. The In Vitro–In Vivo Safety Confirmation of PEG-40 Hydrogenated Castor Oil as a Surfactant for Oral Nanoemulsion Formulation

    PubMed Central

    Rachmawati, Heni; Novel, Miranti Anggraeni; Ayu, Sri; Berlian, Guntur; Tandrasasmita, Olivia Mayasari; Tjandrawinata, Raymond Rubianto; Anggadiredja, Kusnandar

    2017-01-01

    Evaluation on the safety use of high concentration of polyoxyl 40 (PEG-40) hydrogenated castor oil as a surfactant for oral nanoemulsion was performed in Webster mice. As previously reported, nearly 20% of PEG-40 hydrogenated castor oil was used to emulsify the glyceryl monooleate (GMO) as an oil to the aqueous phase. Thermodynamically stable and spontaneous nanoemulsion was formed by the presence of co-surfactant polyethylene glycol 400 (PEG-400). Standard parameters were analyzed for nanoemulsion including particle size and particle size distribution, the surface charge of nanoemulsion, and morphology. To ensure the safety of this nanoemulsion, several cell lines were used for cytotoxicity study. In addition, 5000 mg/kg body weight (BW) of the blank nanoemulsion was given orally to Webster mice once a day for 14 days. Several parameters such as gross anatomy, body weight, and main organs histopathology were observed. In particular, by considering the in vivo data, it is suggested that nanoemulsion composed with a high amount of PEG-40 hydrogenated castor oil is acceptable for oral delivery of active compounds. PMID:28362322

  7. The In Vitro-In Vivo Safety Confirmation of PEG-40 Hydrogenated Castor Oil as a Surfactant for Oral Nanoemulsion Formulation.

    PubMed

    Rachmawati, Heni; Novel, Miranti Anggraeni; Ayu, Sri; Berlian, Guntur; Tandrasasmita, Olivia Mayasari; Tjandrawinata, Raymond Rubianto; Anggadiredja, Kusnandar

    2017-03-31

    Evaluation on the safety use of high concentration of polyoxyl 40 (PEG-40) hydrogenated castor oil as a surfactant for oral nanoemulsion was performed in Webster mice. As previously reported, nearly 20% of PEG-40 hydrogenated castor oil was used to emulsify the glyceryl monooleate (GMO) as an oil to the aqueous phase. Thermodynamically stable and spontaneous nanoemulsion was formed by the presence of co-surfactant polyethylene glycol 400 (PEG-400). Standard parameters were analyzed for nanoemulsion including particle size and particle size distribution, the surface charge of nanoemulsion, and morphology. To ensure the safety of this nanoemulsion, several cell lines were used for cytotoxicity study. In addition, 5000 mg/kg body weight (BW) of the blank nanoemulsion was given orally to Webster mice once a day for 14 days. Several parameters such as gross anatomy, body weight, and main organs histopathology were observed. In particular, by considering the in vivo data, it is suggested that nanoemulsion composed with a high amount of PEG-40 hydrogenated castor oil is acceptable for oral delivery of active compounds.

  8. Lipid nanoparticles: drug localization is substance-specific and achievable load depends on the size and physical state of the particles.

    PubMed

    Kupetz, Eva; Bunjes, Heike

    2014-09-10

    Lipid nanoemulsions and -suspensions are being intensively investigated as carriers for poorly water soluble drugs. The question on where model compounds or probes are localized within the dispersions has been the subject of several studies. However, only little data exists for pharmaceutically relevant molecules in dispersions composed of pharmaceutically relevant excipients. In this work, the localization of drugs and drug-like substances was studied in lipid nanoemulsions and -suspensions. Conclusions about the drug localization were drawn from the relations between lipid mass, specific particle surface area and drug load in the dispersions. Additionally, the achievable drug loads of the liquid and the solid lipid particles were compared. Nanoemulsions and -suspensions comprised trimyristin as lipid matrix and poloxamer 188 as emulsifier and were prepared with different well-defined particle sizes. These pre-formed dispersions were passively loaded with either amphotericin B, curcumin, dibucaine, fenofibrate, mefenamic acid, propofol, or a porphyrin derivative. The physico-chemical properties of the particles were characterized; drug load and lipid content were quantified by UV spectroscopy and high performance liquid chromatography, respectively. For all drugs the passive loading procedure was successful in both emulsions and suspensions. Solid particles accommodate drug molecules preferably at the particle surface. Liquid particles can accommodate drugs at the particle surface as well as in the core; the distribution between the two sites is drug specific. It is also drug specific whether solid or liquid particles yield higher drug loads. As a general rule, smaller particles led to higher drug loads than larger ones. Propofol and the porphyrin derivative displayed eutectic interaction with the lipid and crystal growth after loading, respectively.

  9. Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs.

    PubMed

    Cerpnjak, Katja; Zvonar, Alenka; Gašperlin, Mirjana; Vrečer, Franc

    2013-12-01

    Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.

  10. Fabrication, in-vitro characterization, and enhanced in-vivo evaluation of carbopol-based nanoemulsion gel of apigenin for UV-induced skin carcinoma.

    PubMed

    Jangdey, Manmohan S; Gupta, Anshita; Saraf, Swarnlata

    2017-11-01

    The aim of this study was to develop a potential novel formulation of carbopol-based nanoemulsion gel containing apigenin using tamarind gum emulsifier which was having the smallest droplet size, the highest drug content, and a good physical stability for Skin delivery. Apigenin loaded nanoemulsion was prepared by high speed homogenization method and they were characterized with respect to morphology, zeta potential, differential scanning calorimeter study, and penetration studies. In-vitro release studies and skin permeation of apigenin loaded nanoemulsion by goat abdominal skin was determined using Franz diffusion cell and confocal laser scanning microscope (CLSM). The cytotoxicity of the reported formulation was evaluated in HaCaT Cells (A) and A431 cells (B) by MTT assay. The nanoemulsion formulation showed droplet size, polydispersity index, and zeta potential of 183.31 nm, 0.532, and 31.9 mV, respectively. The nanoemulsions were characterized by TEM demonstrated spherical droplets and FTIR to ensure the compatibility among its ingredients. CLSM showed uniform fluorescence intensity across the entire depth of skin in nanocarriers treatment, indicating high penetrability of nanoemulsion gel through goatskin. The nanoemulsion gel showed toxicity on melanoma (A341) in a concentration range of 0.4-2.0 mg/ml, but less toxicity toward HaCaT cells. The carbopol-based nanoemulsion gel formulation of apigenin possesses better penetrability across goatskin as compared to marketed formulation. Hence, the study postulates that the novel nanoemulsion gel of apigenin can be proved fruitful for the treatment of skin cancer in near future.

  11. Effect of ubiquinol-10 on citral stability and off-flavor formation in oil-in-water (O/W) nanoemulsions.

    PubMed

    Zhao, Qin; Ho, Chi-Tang; Huang, Qingrong

    2013-08-07

    The effects of different concentrations of ubiquinol-10 (Q10H2) on citral's stability were systematically investigated and compared in citral-loaded oil-in-water (O/W) nanoemulsions. Solid phase microextraction gas chromatography (SPME-GC) was employed to monitor the degradation of citral and the formation of off-flavor compounds throughout storage at 25 and 45 °C. The optimum concentration of Q10H2 in the current formulation was determined to be around 0.10 wt % in the system (Q10H2/citral ratio 1:1), which can effectively protect citral from chemical degradation and oxidation. Results suggested, however, that a low concentration of Q10H2 may induce the majority of the ubisemiquinone (Q10(•-))/ubiquinone (Q10) redox transition, which possibly endowed Q10H2 with pro-oxidant properties. Further increase in Q10H2 concentration beyond a certain value also hindered its effect due to the complex properties of radicals involved and the overall environment encountered. With appropriate concentrations of Q10H2 presented in the system, major citral oxidation off-flavor compounds (p-cresol, α,p-dimethylstyrene, p-methylacetophenone), and some of the lipid degradation products can be inhibited to lower levels. In contrast, ubiquinone-10 (Q10) had a negligible effect on citral's chemical stability and off-flavor generation.

  12. Effect of novel bioactive edible coatings based on jujube gum and nettle oil-loaded nanoemulsions on the shelf-life of Beluga sturgeon fillets.

    PubMed

    Gharibzahedi, Seyed Mohammad Taghi; Mohammadnabi, Sara

    2017-02-01

    Effect of jujube gum (JG; 4, 8 and 12% wt)-based nanoemulsions (NEs) containing nettle essential oil (NEO; 2, 3.5 and 5% wt) as new edible coatings was investigated to preserve Beluga sturgeon fillets (BSFs) during 15 day-refrigerated storage at 4°C. Physical (weight loss, cooking loss, color and texture), chemical (pH, FFA, PV, TBARS and TVB-N), microbiological (total and psychrotrophic bacterial counts), and sensorial characteristics of BSFs were kinetically analyzed. Preliminary studies showed that the NEs formulated with NEO lower than 5% at all JG concentrations were able to form stable coating solutions owing to the highest short-term stability (>90%) and entrapment efficiency (94.4-98.3%). Edible NE coating formulated with 12% JG and 3.5% NEO as a novel antimicrobial and antioxidant biomaterial exhibited the lowest weight and cooking losses, pH changes, textural and color deterioration, lipid oxidation and microbial growth in BSFs refrigerated over a period of 15days (P<0.05).

  13. Topical Nanoemulsion Therapy Reduces Bacterial Wound Infection and Inflammation Following Burn Injury

    PubMed Central

    Hemmila, Mark R.; Mattar, Aladdein; Taddonio, Michael A.; Arbabi, Saman; Hamouda, Tarek; Ward, Peter A.; Wang, Stewart C.; Baker, James R.

    2010-01-01

    Background Nanoemulsions are broadly antimicrobial oil-in-water emulsions containing nanometer-sized droplets stabilized with surfactants. We hypothesize that topical application of a nanoemulsion compound (NB-201) can attenuate burn wound infection. In addition to reducing infection, nanoemulsion therapy may modulate dermal inflammatory signaling and thereby lessen inflammation following thermal injury. Methods Male Sprague-Dawley rats underwent a 20% total body surface area (TBSA) scald burn to create a partial thickness burn injury. Animals were resuscitated with Ringer’s lactate and the wound covered with an occlusive dressing. Eight hours after injury, the burn wound was inoculated with 1×106 CFU of Pseudomonas aeruginosa. NB-201, NB-201 placebo, 5% mafenide acetate solution or 0.9% saline (control) was applied onto the wound at 16 and 24 hrs following burn injury. Skin was harvested 32 hrs post-burn for quantitative wound culture and determination of inflammatory mediators in tissue homogenates. Results NB-201 reduced mean bacterial growth in the burn wound by a thousand fold, with only 11% animals having P. aeruginosa counts greater than 105 CFU/g tissue versus 91% in the control group (p<0.0001). Treatment with NB-201 attenuated neutrophil sequestration in the treatment group as measured by myeloperoxidase assay and by histology. It also, significantly reduced levels of pro-inflammatory cytokines (IL-1β and IL-6) and the degree of hair follicle cell apoptosis in skin when compared to saline-treated controls. Conclusions Topical NB-201 substantially reduced bacterial growth in a partial thickness burn model. This reduction in the level of wound infection was associated with an attenuation of the local dermal inflammatory response and diminished neutrophil sequestration. NB-201 represents a novel potent antimicrobial and antiinflammatory treatment for use in burn wounds. PMID:20189619

  14. Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury.

    PubMed

    Hemmila, Mark R; Mattar, Aladdein; Taddonio, Michael A; Arbabi, Saman; Hamouda, Tarek; Ward, Peter A; Wang, Stewart C; Baker, James R

    2010-09-01

    Nanoemulsions are broadly antimicrobial oil-in-water emulsions containing nanometer-sized droplets stabilized with surfactants. We hypothesize that topical application of a nanoemulsion compound (NB-201) can attenuate burn wound infection. In addition to reducing infection, nanoemulsion therapy may modulate dermal inflammatory signaling and thereby lessen inflammation following thermal injury. Male Sprague-Dawley rats underwent a 20% total body surface area scald burn to create a partial-thickness burn injury. Animals were resuscitated with Ringer's lactate solution and the wound covered with an occlusive dressing. At 8 hours after injury, the burn wound was inoculated with 1 x 10(6) colony-forming units (CFUs) of Pseudomonas aeruginosa. NB-201, NB-201 placebo, 5% mafenide acetate solution, or 0.9% saline (control) was applied onto the wound at 16 and 24 hours after burn injury. Skin was harvested 32 hours postburn for quantitative wound culture and determination of inflammatory mediators in tissue homogenates. NB-201 decreased mean bacterial growth in the burn wound by 1,000-fold, with only 13% (3/23) of animals having P. aeruginosa counts greater than 10(5) CFU/g tissue versus 91% (29/32) in the control group (P < .0001). Treatment with NB-201 attenuated neutrophil sequestration in the treatment group as measured by myeloperoxidase assay and by histology. It also significantly decreased levels of proinflammatory cytokines (interleukin [IL]-1beta and IL-6) and the degree of hair follicle cell apoptosis in skin compared to saline-treated controls. Topical NB-201 substantially decreased bacterial growth in a partial-thickness burn model. This decrease in the level of wound infection was associated with an attenuation of the local dermal inflammatory response and diminished neutrophil sequestration. NB-201 represents a novel potent antimicrobial and anti-inflammatory treatment for use in burn wounds. Copyright 2010 Mosby, Inc. All rights reserved.

  15. [Ion-sensitive nanoemulsion-in situ gel system for ophthalmic delivery of flurbiprofen axetil].

    PubMed

    Shen, Jin-Qiu; Gan, Yong; Gan, Li; Zhu, Chun-Liu; Zhu, Jia-Bi

    2010-01-01

    The aim of the study is to prepare flurbiprofen axetil nanoemulsion-in situ gel system (FBA/NE-ISG) and observe its ocular pharmacokinetics, rheological behavior, TEM images, irritation and cornea retention. Production of nanoemulsion was based on high-speed shear and homogenization process, and then mixed with gellan gum to prepare FBA/NE-ISG. Rheological study showed that FBA/NE-ISG possesses strong gelation capacity and its viscosity and elastic modulus increases by 2 Pa*s and 5 Pa respectively when mixed with artificial tear at the ratio of 40 : 7. TEM images suggested no significant changes in particle morphology of the pre and post gelation. Good ocular compatibility of FBA/NE-ISG was testified by the irritation test based on histological examination. In vivo fluorescence imaging system was applied to investigate the characteristics of cornea retention, and the results indicated that the nanoemulsion-in situ gel (NE-ISG) prolonged the cornea retention time significantly since K(NE-ISG) (0.008 5 min(-1) was much lower compared with flurbiprofen sodium eye drops (FB-Na, 0.03% w/v) of which the K(Eye drops) was 0.105 2 min(-1), indicated that the cornea retention time of NE-ISG was prolonged significantly. Pharmacokinetics of FBA/NE-ISG in rabbit aqueous humor was studied by cornea puncture, the MRT (12.3 h) and AUC(0-12h) (126.8 microg x min x mL(-1)) of FBA/NE-ISG was 2.7 and 2.9 times higher than that of the flurbiprofen sodium eye drops respectively, which meant that the ocular bioavailability was improved greatly by the novel preparation. Therefore, FBA/NE-ISG can enhance the ocular bioavailability by prolonging drug corneal retention significantly. What's more, encapsulated by emulsion droplets prodrug flurbiprofen (FBA) instead of flurbiprofen (FB) can reduce the ocular irritation.

  16. Plum coatings of lemongrass oil-incorporating carnauba wax-based nanoemulsion.

    PubMed

    Kim, In-Hah; Lee, Hanna; Kim, Jung Eun; Song, Kyung Bin; Lee, Youn Suk; Chung, Dae Sung; Min, Sea C

    2013-10-01

    Nanoemulsions containing lemongrass oil (LO) were developed for coating plums and the effects of the nanoemulsion coatings on the microbial safety and physicochemical storage qualities of plums during storage at 4 and 25 °C were investigated. The emulsions used for coating were produced by mixing a carnauba wax-based solution (18%, w/w) with LO at various concentrations (0.5% to 4.0%, w/w) using dynamic high pressure processing at 172 MPa. The coatings were evaluated for their ability to inhibit the growth of Salmonella Typhimurium and Escherichia coli O157:H7 and their ability to preserve various physicochemical qualities of plums. Uniform and continuous coatings on plums, formed with stable emulsions, initially inhibited S. Typhimurium and E. coli O157:H7 by 0.2 to 2.8 and 0.8 to 2.7 log CFU/g, respectively, depending on the concentration of LO and the sequence of coating. The coatings did not significantly alter the flavor, fracturability, or glossiness of the plums. The antimicrobial effects of the coatings against S. Typhimurium and E. coli O157:H7 were demonstrated during storage at 4 and 25 °C. The coatings reduced weight loss and ethylene production by approximately 2 to 3 and 1.4 to 4.0 fold, respectively, and also retarded the changes in lightness and the concentration of phenolic compounds in plums during storage. The firmness of coated plums was generally higher than uncoated plums when stored at 4 °C and plum respiration rates were reduced during storage. Coatings containing nanoemulsions of LO have the potential to inhibit Salmonella and E. coli O157:H7 contamination of plums and may extend plum shelf life.

  17. Inertial cavitation in theranostic nanoemulsions with simultaneous pulsed laser and low frequency ultrasound excitation

    NASA Astrophysics Data System (ADS)

    Arnal, Bastien; Wei, Chen-Wei; Xia, Jinjun; Pelivanov, Ivan M.; Lombardo, Michael; Perez, Camilo; Matula, Thomas J.; Pozzo, Danilo; O'Donnell, Matthew

    2014-03-01

    Ultrasound-induced inertial cavitation is a mechanical process used for site-localized therapies such as non-invasive surgery. Initiating cavitation in tissue requires very high intensity focused ultrasound (HIFU) and low-frequencies. Hence, some applications like thrombolysis require targeted contrast agents to reduce peak intensities and the potential for secondary effects. A new type of theranostic nanoemulsion has been developed as a combined ultrasound (US)/photoacoustic(PA) agent for molecular imaging and therapy. It includes a nanoscale emulsion core encapsulated with a layer of gold nanospheres at the water/ oil interface. Its optical absorption exhibits a spectrum broadened up to 1100 nm, opening the possibility that 1064 nm light can excite cavitation nuclei. If optically-excited nuclei are produced at the same time that a low-frequency US wave is at peak negative pressure, then highly localized therapies based on acoustic cavitation may be enabled at very low US pressures. We have demonstrated this concept using a low-cost, low energy, portable 1064 nm fiber laser in conjunction with a 1.24 MHz US transducer for simultaneous laser/US excitation of nanoemulsions. Active cavitation detection from backscattered signals indicated that cavitation can be initiated at very low acoustic pressures (less than 1 MPa) when laser excitation coincides with the rarefaction phase of the acoustic wave, and that no cavitation is produced when light is delivered during the compressive phase. US can sustain cavitation activity during long acoustic bursts and stimulate diffusion of the emulsion, thus increasing treatment speed. An in vitro clot model has been used to demonstrate combined US and laser excitation of the nanoemulsion for efficient thrombolysis.

  18. Characterization of Y2BaCuO5 nanoparticles synthesized by nano-emulsion method

    NASA Astrophysics Data System (ADS)

    Li, Fang; Vipulanandan, Cumaraswamy

    2007-10-01

    Nanoscale yttrium-barium-copper oxide (Y2BaCuO5, Y211) particles were synthesized using the emulsion method and the solution method. The basic water-in-oil (w/o) emulsion system consisted of n-octane (continuous oil phase), cetyltrimethylammonium bromide (cationic surfactant), butanol (cosurfactant) and water. The composition of the emulsion system was varied and characterized by measuring the conductivity of the solutions and droplet size. The droplet size of emulsion was determined by using the dynamic light scattering method. The water content, cosurfactant content, and surfactant/ n-octane ratio affected the droplet size which was in the range of 3-8 nm, and hence the w/o emulsion system was referred to as a nano-emulsion system. A model was used to verify the droplet size. The influence of salt (Y2(NO3)3) content on the droplet size was investigated and the addition of salt reduced the droplet size. The effects of reaction time and temperature on the Y211 particle sizes were also investigated. The particles were characterized using the TEM, SEM, and XRD. Nanoparticles produced by the nano-emulsion method were calcined at 850°C to form the Y211 phase as compared to solid state processing temperature of 1050°C. Based on the TEM analysis, the average diameter of the Y211 particles produced using the nano-emulsion method was in the range of 30-100 nm. The effect of adding 15% Y211 nanoparticles to the superconductor YBCO-123 as flux pinning centers, was investigated, and the transition temperature was reduced by 3 K.

  19. Preparation and Thermal Properties of Fatty Alcohol/Surfactant/Oil/Water Nanoemulsions and Their Cosmetic Applications.

    PubMed

    Okamoto, Toru; Tomomasa, Satoshi; Nakajima, Hideo

    2016-01-01

    Physicochemical properties of oil-in-water (O/W) emulsions containing fatty alcohols and surfactants have been investigated with the aim of developing new formulations that are less viscous and more transparent than conventional milky lotions, as well as for providing greater skin-improving effects. O/W-based creams can be converted to low viscosity milky lotions following their emulsification with a homogenizer at temperatures greater than the transition temperatures of their molecular assemblies (α-gel). The stability of the O/W emulsions evaluated in the current study increased as the transition temperatures of the molecular assemblies formed from their fatty alcohol and surfactant constituents increased. A decrease in the emulsion droplet size led to the formation of a new formulation, which was transparent in appearance and showed a very low viscosity. The absence of a molecular assembly (α-gel) formed by the fatty alcohol and surfactant molecules in the aqueous phase allowed for the formation of a stable transparent and low viscosity nanoemulsion. Furthermore, this decrease in droplet size led to an increase in the interfacial area of the emulsion droplets, with almost all of the fatty alcohol and surfactant molecules being adsorbed on the surfaces of the emulsion droplets. This was found to be important for preparing a stable transparent formulation. Notably, this new formulation exhibited high occlusivity, which was equivalent to that of an ordinary cosmetic milky lotion, and consequently provided high skin hydration. The nanoemulsion was destroyed following its application to the skin, which led to the release of the fatty alcohol and surfactant molecules from the surface of the nanoemulsion into the aqueous phase. These results therefore suggest that the fatty alcohol and surfactant molecules organized the molecular assembly (α-gel) and allowed for the reconstruction of the network structure.

  20. Bio-active nanoemulsions enriched with gold nanoparticle, marigold extracts and lipoic acid: In vitro investigations.

    PubMed

    Guler, Emine; Barlas, F Baris; Yavuz, Murat; Demir, Bilal; Gumus, Z Pinar; Baspinar, Yucel; Coskunol, Hakan; Timur, Suna

    2014-09-01

    A novel and efficient approach for the preparation of enriched herbal formulations was described and their potential applications including wound healing and antioxidant activity (cell based and cell free) were investigated via in vitro cell culture studies. Nigella sativa oil was enriched with Calendula officinalis extract and lipoic acid capped gold nanoparticles (AuNP-LA) using nanoemulsion systems. The combination of these bio-active compounds was used to design oil in water (O/W) and water in oil (W/O) emulsions. The resulted emulsions were characterized by particle size measurements. The phenolic content of each nanoemulsion was examined by using both colorimetric assay and chromatographic analyses. Two different methods containing cell free chemical assay (1-diphenyl-2-picrylhydrazyl method) and cell based antioxidant activity test were used to evaluate the antioxidant capacities. In order to investigate the bio-activities of the herbal formulations, in vitro cell culture experiments, including cytotoxicity, scratch assay, antioxidant activity and cell proliferation were carried out using Vero cell line as a model cell line. Furthermore, to monitor localization of the nanoemulsions after application of the cell culture, the cell images were monitored via fluorescence microscope after FITC labeling. All data confirmed that the enriched N. sativa formulations exhibited better antioxidant and wound healing activity than N. sativa emulsion without any enrichment. In conclusion, the incorporation of AuNP-LA and C. officinalis extract into the N. sativa emulsions significantly increased the bio-activities. The present work may support further studies about using the other bio-active agents for the enrichment of herbal preparations to strengthen their activities. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect.

    PubMed

    Zhu, Lifei; Li, Miao; Dong, Junxing; Jin, Yiguang

    2015-08-01

    Acute lung injury (ALI) is a severe disease, leading to death if not treated quickly. An emergency medicine is necessary for ALI therapy. Dimethyl silicone (DMS) is an effective agent to defoam the bubbles in the lung induced by ALI. However, DMS aerosols, a marketed formulation of DMS, affect environments and will be limited in the future. Here we firstly report a dry nanoemulsion inhalation for pulmonary delivery. Novel DMS dry nanoemulsion inhalations (DSNIs) were developed in this study. The optimal formulation of stable and homogenous DMS nanoemulsions (DSNs) was composed of Cremophor RH40/PEG 400/DMS (4:4:2, w/w/w) and water. The DSNs showed the tiny size of 19.8 nm, the zeta potential of -9.66 mV, and the low polydispersity index (PDI) of 0.37. The type of DSNs was identified as oil-in-water. The DSNs were added with mannitol followed by freeze-drying to obtain the DSNIs that were loose white powders, showed good fluidity, and were capable of rapid reconstitution to DSNs. The DSNs could adhere on the surfaces of lyophilized mannitol crystals. The aerodynamic diameter of DSNIs was 4.82 μm, suitable for pulmonary inhalation. The in vitro defoaming rate of DSNIs was 1.25 ml/s, much faster than those of the blank DSNIs, DMS, and DMS aerosols. The DSNIs showed significantly higher anti-ALI effect on the ALI rat models than the blank DSNIs and the DMS aerosols according to lung appearances, histological sections, and lung wet weight/dry weight ratios. The DSNIs are effective anti-ALI nanomedicines. The novel DMS formulation is a promising replacement of DMS aerosols.

  2. Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions

    PubMed Central

    Liu, Ting-ting; Mu, Li-Qiu; Dai, Wei; Wang, Chuan-bang; Liu, Xin-Yi; Xiang, Da-Xiong

    2016-01-01

    The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL−1, determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg−1, calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration–time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO. PMID:27330293

  3. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    PubMed

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man.

  4. Uterine Tumour Resembling Ovarian Sex Cord Tumour- A Rare Entity

    PubMed Central

    Ilhan, Tolgay Tuyan; Gül, Ayhan; Ugurluoglu, Ceyhan; Çelik, Çetin

    2016-01-01

    Uterine Tumour Resembling Ovarian Sex-Cord Tumours (UTROSCTs) are an extremely rare type of uterine body tumours arising from the endometrial stroma. Epidemiology, aetiology, pathogenesis, management and natural history of UTROSCTs are still a question of debate, as there is little available data in the literature. Although rare, the possibility of UTROSCTs should be kept in mind, when a patient presents with abnormal bleeding and an enlarged uterus. UTROSCTs appear dirty white/cream-coloured, gelatinous, well-circumscribed mass with smooth surface on macroscopic examination. We present a rare case of endometrial stromal tumour with sex-cord-like differentiation which was successfully treated by hysterectomy with bilateral salpingo-oophorectomy. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. PMID:28208949

  5. Adenomyomatosis of the gallbladder resembling honeycomb in a child.

    PubMed

    Akçam, Mustafa; Buyukyavuz, Ilker; Ciriş, Metin; Eriş, Naim

    2008-09-01

    Adenomyomatosis of the gallbladder is believed to be an uncommon pathologic condition of the gallbladder in childhood. Only three pediatric cases have been described in the literature up to now. Honeycomb gallbladder has been described in two adult patients; no patients have been reported in childhood until now. To the best of our knowledge, we report here the first case of adenomyomatosis of the gallbladder which resembled honeycomb, in a 9-year-old girl presented with recurrent abdominal pain. The diagnosis was made by ultrasound, and confirmed by magnetic resonance cholangiopancreatography and finally cholecystectomy. In conclusion, ultrasound scanning performed more generally in children presenting with recurrent abdominal pain might lead to accurate diagnosis of adenomyomotosis of the gallbladder during childhood.

  6. Differentiated human stem cells resemble fetal, not adult, β cells.

    PubMed

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This st