Mitochondrial mechanisms of neuronal rescue by F-68, a hydrophilic Pluronic block co-polymer, following acute substrate deprivation.

PubMed

Wang, Janice C; Bindokas, Vytautas P; Skinner, Matthew; Emrick, Todd; Marks, Jeremy D

2017-10-01

Global brain ischemia can lead to widespread neuronal death and poor neurologic outcomes in patients. Despite detailed understanding of the cellular and molecular mechanisms mediating neuronal death following focal and global brain hypoxia-ischemia, treatments to reduce ischemia-induced brain injury remain elusive. One pathway central to neuronal death following global brain ischemia is mitochondrial dysfunction, one consequence of which is the cascade of intracellular events leading to mitochondrial outer membrane permeabilization. A novel approach to rescuing injured neurons from death involves targeting cellular membranes using a class of synthetic molecules called Pluronics. Pluronics are triblock copolymers of hydrophilic poly[ethylene oxide] (PEO) and hydrophobic poly[propylene oxide] (PPO). Evidence is accumulating to suggest that hydrophilic Pluronics rescue injured neurons from death following substrate deprivation by preventing mitochondrial dysfunction. Here, we will review current understanding of the nature of interaction of Pluronic molecules with biological membranes and the efficacy of F-68, an 80% hydrophilic Pluronic, in rescuing neurons from injury. We will review data indicating that F-68 reduces mitochondrial dysfunction and mitochondria-dependent death pathways in a model of neuronal injury in vitro, and present new evidence that F-68 acts directly on mitochondria to inhibit mitochondrial outer membrane permeabilization. Finally, we will present results of a pilot, proof-of-principle study suggesting that F-68 is effective in reducing hippocampal injury induced by transient global ischemia in vivo. By targeting mitochondrial dysfunction, F-68 and other Pluronic molecules constitute an exciting new approach to rescuing neurons from acute injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbial liquefaction of peat for the production of synthetic fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunasekaran, M.

1988-01-01

Objectives of this study were: to evaluate the potential of using various microorganisms to hydrolyse and liquify peat; to determine the optimal conditions for peat hydrolysis and liquefaction; to study the co-metabolizable substances; to separate the compounds present in liquified peat by alumina and silica acid chromatography and capillary gas chromatography; and to identify the compounds in liquified peat by capillary GC-Mass spectrometry. Organisms used in the study include: Coprinus comatus, Coriolus hirsutus, Ganoderma lucidum, Lentinus edodes, Lenzites trabea, Phanerochaete chrysosporium, Pleurotus ostreatus, P. sapidus, Polyporus adjustus, Neurospora sitophila, Rhizophus arrhizus, Bacillus subtilis, Acinetobacter sp. and Alcaligenes sp. The fungimore » were maintained and cultivated in potato dextrose agar at 30 C. The bacteria were maintained in nutrient agar at 30 C. We have also initiated work on coal solubilization in addition to the studies on peat liquefaction. A relatively new substratum or semi-solid base for culture media called Pluronic F-127, or Polyol (BASF, New Jersey). Objectives of this study were: (1) to study the growth patterns of Candida ML 13 on pluronic as substratum; (2) to determine the rate of microbial coal solubilization on pluronic F-127 amended in different growth media; (3) to separate the mycelial mat of Candida ML 13 from unsolubilized coal particles and solubilized coal products from pluronic F-127; (4) to determine the effects of pH on microbial coal solubilization in pluronic F-127 media; (5) the effect of concentration of pluronic F-127 in media on coal solubilization; and, (6) to study the role of extracellular factors secreted by Candida ML 13 on coal solubilization in pluronic F-127 media. Results are discussed. 4 refs.« less

Hard Pd Nanorods in the Soft Surfactant Mixture of CTAB and Pluronics: Seedless Synthesis and Their Self-Assembly.

PubMed

Song, Hyon-Min; Zink, Jeffrey I

2018-04-10

Seedless synthesis of Pd nanorods and their self-assembly into the layered smectic ordering are described. Aqueous Pluronic triblock copolymers (14.3-35.7%) are used as a soft template along with cetyltrimethylammonium bromide for inducing one-dimensional growth of Pd nanorods. Pluronic triblock copolymers are probably the most used polymer surfactants, and they are composed of poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO triblocks. Neither pH adjustment nor AgNO 3 and other additives, such as poly(vinyl pyrrolidone) and ethylene glycol, are required to obtain Pd nanorods. Sonochemical synthesis at 43 °C, followed by thermal annealing for 1 h at 65 °C produces Pd nanorods with the aspect ratio from 3.1 (17.9%, Pluronic L-64) to 6.7 (35.7%, Pluronic P-123). Two-dimensional self-assembly of the nanorods is observed, and both nematic ordering between the mesogens and smectic ordering between the layers is identified. Micellar hydrophobic PPO with hydrated PEO coronas are known to self-assemble into many crystalline orders, including cubic, hexagonal, lamellar, and inverse hexagonal mesophases, which extend into cylindrical micelles with increasing temperature. Relatively small size of Pluronic copolymers with regard to general polymers, but rather large size of their micelles and their tendency to organize into crystalline mesophases are thought to contribute to the anisotropic growth of Pd nanorods.

Modified release from lipid bilayer coated mesoporous silica nanoparticles using PEO–PPO–PEO triblock copolymers [Modified release from lipid bilayer coated mesoporous silica nanoparticles using PEO PPO PEO triblock copolymers

DOE PAGES

Rahman, Masoud; Yu, Erick; Forman, Evan; ...

2014-08-20

Triblock copolymers comprised of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, or trade name Pluronic) interact with lipid bilayers to increase their permeability. Here we demonstrate a novel application of Pluronic L61 and L64 as modification agents in tailoring the release rate of a molecular indicator species from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer-coated superparamagnetic Fe 3O 4/mesoporous silica coreshell nanoparticles. Lastly, we show there is a direct relationship between Pluronic concentration and the indicator molecule release, suggesting Pluronic may be useful for the controlled release of drugs from lipid bilayer-coated carriers.

Pluronic Microemulsions as Nanoreservoirs for Extraction of Bupivacaine from Normal Saline

PubMed Central

Varshney, Manoj; Morey, Timothy E.; Shah, Dinesh O.; Flint, Jason A.; Moudgil, Brij M.; Seubert, Christoph N.

2013-01-01

We hypothesized that custom-designed microemulsions would effectively scavenge compounds from bulk media. Pluronic-based oil-in-water microemulsions were synthesized that efficiently reduced the free concentration of the local anesthetic bupivacaine in 0.9% NaCl. Both the molecular nature and concentration of the constituents in the microemulsions significantly affected extraction efficiencies. Pluronic F127-based microemulsions extracted bupivacaine more efficiently than microemulsions synthesized using other Pluronic surfactants (L44, L62, L64, F77, F87, F88, P104). Extraction was markedly increased by addition of fatty acid sodium salts due to greater oil/water interface area, increased columbic interaction between bupivacaine and fatty acids sodium salt, and greater surface activity. These data suggest that oil-in-water microemulsions may be an effective agent to treat cardiotoxicity caused by bupivacaine or other lipophilic drugs. PMID:15099093

Mass-action model analysis of the apparent molar volume and heat capacity of pluronics in water and liposome suspensions at 25 °C.

PubMed

Quirion, François; Meilleur, Luc; Lévesque, Isabelle

2013-07-09

Pluronics are block copolymers composed of a central block of polypropylene oxide and two side chains of polyethylene oxide. They are used in water to generate aggregates and gels or added to phospholipid suspensions to prepare microparticles for drug delivery applications. The structure of these systems has been widely investigated. However, little is known about the mechanisms leading to these structures. This investigation compares the apparent molar volumes and heat capacities of Pluronics F38, F108, F127, P85, P104, and P103 at 25 °C in water and in the presence of lecithin liposomes. The changes in molar volumes, heat capacities, and enthalpies generated by a mass-action model are in good agreement with the loss of hydrophobic hydration of the polypropylene oxide central block of the Pluronics. However, the molecularity of the endothermic transitions is much smaller than the aggregation numbers reported in the literature for the same systems. It is suggested that Pluronics go through dehydration of their central block to form unimolecular or small entities having a hydrophobic polypropylene oxide core. In water, these entities would assemble athermally to form larger aggregates. In the presence of liposomes, they would be transferred into the hydrophobic lecithin bilayers of the liposomes. Light transmission experiments suggest that the liposome suspensions are significantly altered only when the added Pluronics are in the dehydrated state.

Development of chitosan/poly-γ-glutamic acid/pluronic/curcumin nanoparticles in chitosan dressings for wound regeneration.

PubMed

Lin, Yu-Hsin; Lin, Jui-Hsiang; Hong, Ya-Shiuan

2017-01-01

The hydrophobic polyphenol curcumin has anti-inflammatory, antimicrobial, and wound-healing properties that warrant its pharmacological consideration. We report a curcumin nanoparticle with a tripolymeric composite that can be used as a delivery device for wound healing. The present composite nanoparticles were prepared with three biocompatible polymers of chitosan, poly-γ-glutamic acid, and pluronic using a simple ionic gelation technology. Pluronic was used to enhance the solubility of curcumin in chitosan/poly-γ-glutamic acid nanoparticles, leading to the incorporation of chitosan/poly-γ-glutamic acid/pluronic/curcumin nanoparticles into chitosan membranes, and reduced inflammation and bacterial infection during wound regeneration. Nanoparticles were of 193.1 ± 8.9 nm and had a zeta potential of 20.6 ± 2.4 mV. Moreover, in vitro analyses indicated controlled curcumin release in a simulated skin tissue model. Subsequent in vivo studies show that chitosan wound dressing containing chitosan/poly-γ-glutamic acid/pluronic/curcumin nanoparticles promoted neocollagen regeneration and tissue reconstruction. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 81-90, 2017. © 2015 Wiley Periodicals, Inc.

Coarse grained study of pluronic F127: Comparison with shorter co-polymers in its interaction with lipid bilayers and self-aggregation in water

NASA Astrophysics Data System (ADS)

Wood, I.; Martini, M. F.; Albano, J. M. R.; Cuestas, M. L.; Mathet, V. L.; Pickholz, M.

2016-04-01

The aim of this work is to understand the interactions of the poloxamer Pluronic F127, with lipid bilayers and its ability to self-associate in an aqueous environment. Molecular dynamics simulations at the coarse-grain scale were performed to address the behavior of single Pluronic F127 and shorter poloxamers unimers in palmitoyl-oleoyl-phosphatidyl-choline model membranes. According to the initial conditions and the poly-ethylene oxide/poly-propylene oxide composition, in water phase the unimer chain collapses into a coil conformation or adopts an interphacial U-shaped - or membrane spanning - distribution. A combination of poly-propylene oxide length, and the poly-ethylene oxide ability to cover poly-propylene oxide, is determinant for the conformation adopted by the unimer in each phase. Results of the simulations showed molecular evidence of strong interaction between Pluronic F127 and model membranes both in stable U-shaped and span conformations. The knowledge of this interaction could contribute to improve drug permeation. Additionally, we investigated the aggregation of one hundred Pluronic F127 unimers in water forming a micelle-like structure, suitable to be used as drug delivery system models.

Surfactant-assisted water exposed electrospinning of novel super hydrophilic polycaprolactone based fibers.

PubMed

Zargarian, S Sh; Haddadi-Asl, V

2017-08-01

Hybrid scaffolds prepared by blend electrospinning of Polycaprolactone and Pluronic solution benefit from enhanced fiber hydrophilicity and may offer satisfactory cell attachment and proliferation. To improve hybrid scaffold wettability and water swelling ratio, adequate amount of hydrophilic polymer is required; though this amount is limited by fiber surface enrichment of Pluronic and cannot be exceeded without affecting the scaffold mechanical properties. To overcome this problem, a routine blend electrospinning setup was modified by exposing the blend solution to water in order to attract Pluronic chains toward the surface of the charged jet. Morphology of scaffolds produced by the routine blend electrospinning and modified method was studied. A 50 nm thick Pluronic layer with linty appearance on the surface of the fibers fabricated by the modified method was detected. Drug-loaded fibers from modified method showed a moderate initial burst and then a prolonged release period while an abnormal two-stage phased release profile was observed for the routine blend method. The latter was associated to Pluronic/drug accumulations within the fibers fabricated by the routine method which resulted in fiber disintegration and a subsequent second burst release.

Mesoscopic Simulations of Adsorption and Association of PEO-PPO-PEO Triblock Copolymers on a Hydrophobic Surface: From Mushroom Hemisphere to Rectangle Brush.

PubMed

Song, Xianyu; Zhao, Shuangliang; Fang, Shenwen; Ma, Yongzhang; Duan, Ming

2016-11-08

The dissipative particle dynamics (DPD) method is used to investigate the adsorption behavior of PEO-PPO-PEO triblock copolymers at the liquid/solid interface. The effect of molecular architecture on the self-assembled monolayer adsorption of PEO-PPO-PEO triblock copolymers on hydrophobic surfaces is elucidated by the adsorption process, film properties, and adsorption morphologies. The adsorption thicknesses on hydrophobic surfaces and the diffusion coefficient as well as the aggregation number of Pluronic copolymers in aqueous solution observed in our simulations agree well with previous experimental and numerical observations. The radial distribution function revealed that the ability of self-assembly on hydrophobic surfaces is P123 > P84 > L64 > P105 > F127, which increased with the EO ratio of the Pluronic copolymers. Moreover, the shape parameter and the degree of anisotropy increase with increasing molecular weight and mole ratio of PO of the Pluronic copolymers. Depending on the conformation of different Pluronic copolymers, the morphology transition of three regimes on hydrophobic surfaces is present: mushroom or hemisphere, progressively semiellipsoid, and rectangle brush regimes induced by decreasing molecular weight and mole ratio of EO of Pluronic copolymers.

Effect of chain length on binding of fatty acids to Pluronics in microemulsions.

PubMed

James-Smith, Monica A; Shekhawat, Dushyant; Cheung, Sally; Moudgil, Brij M; Shah, Dinesh O

2008-03-15

We investigated the effect of fatty acid chain length on the binding capacity of drug and fatty acid to Pluronic F127-based microemulsions. This was accomplished by using turbidity experiments. Pluronic-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated Amitriptyline, an antidepressant drug. Sodium salts of C(8), C(10), or C(12) fatty acid were used in preparation of the microemulsion and the corresponding binding capacities were observed. It has been previously determined that, for microemulsions prepared with sodium caprylate (C(8) fatty acid soap), a maximum of 11 fatty acid molecules bind to the microemulsion per 1 molecule of Pluronic F127 and a maximum of 12 molecules of Amitriptyline bind per molecule of F127. We have found that with increasing the chain length of the fatty acid salt component of the microemulsion, the binding capacity of both the fatty acid and the Amitriptyline to the microemulsion decreases. For sodium salts of C(8), C(10) and C(12) fatty acids, respectively, a maximum of approximately 11, 8.4 and 8.3 molecules of fatty acid molecules bind to 1 Pluronic F127 molecule. We propose that this is due to the decreasing number of free monomers with increasing chain length. As chain length increases, the critical micelle concentration (cmc) decreases, thus leading to fewer monomers. Pluronics are symmetric tri-block copolymers consisting of propylene oxide (PO) and ethylene oxide (EO). The polypropylene oxide block, PPO is sandwiched between two polyethylene oxide (PEO) blocks. The PEO blocks are hydrophilic while PPO is hydrophobic portion in the Pluronic molecule. Due to this structure, we propose that the fatty acid molecules that are in monomeric form most effectively diffuse between the PEO "tails" and bind to the hydrophobic PPO groups.

Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis

PubMed Central

Mady, Fatma M; Essa, Hanaa; El-Ammawi, Tarek; Abdelkader, Hamdy; Hussein, Amal K

2016-01-01

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD. PMID:27022248

Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis.

PubMed

Mady, Fatma M; Essa, Hanaa; El-Ammawi, Tarek; Abdelkader, Hamdy; Hussein, Amal K

2016-01-01

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD.

Determination of drug and fatty acid binding capacity to pluronic f127 in microemulsions.

PubMed

James-Smith, Monica A; Shekhawat, Dushyant; Moudgil, Brij M; Shah, Dinesh O

2007-02-13

We propose that one can deduce very insightful information regarding the drug and fatty acid binding capacity of microemulsions through simple turbidity experiments. Pluronic F127-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated amitriptyline, an antidepressant drug. We observed that, above certain Pluronic F127 concentrations, turbidity was never observed, irrespective of how much amitriptyline was added to the microemulsion. We also observed that whenever sodium caprylate fatty acid was not included in the microemulsion formulation, turbidity never occurred. On the basis of these findings, we were able to determine the point at which all sodium caprylate present in the microemulsion formulation was bound to the F127 in the microemulsion (i.e., no fatty acid was free in the bulk in monomer form). By the same logic we were also able to determine how much amitriptyline was binding to the microemulsions. We also measured the dynamic surface tension, foamability, and fabric wetting time of the microemulsion formulations to further prove the hypothesis that all fatty acid is bound to the F127 in the microemulsion above a critical Pluronic F127 concentration. On the basis of this research, we have concluded that there are approximately 11 molecules of sodium caprylate fatty acid bound per molecule of Pluronic F127 and approximately 12 molecules of amitriptyline bound per molecule of Pluronic F127 in the optimal microemulsion formulation. These findings give us valuable information about the charge density at the oil/water interface and about the mechanism of binding of the drug to the microemulsion.

Pluronic® F-127 and Pluronic Lecithin Organogel (PLO): main features and their applications in topical and transdermal administration of drugs.

PubMed

Almeida, Hugo; Amaral, Maria Helena; Lobão, Paulo; Lobo, José Manuel Sousa

2012-01-01

Topical drug treatment aims at providing high concentrations of drugs at the site of application so as to avoid adverse systemic effects associated with oral administration. Smart polymers, or stimuli-responsive polymers, are able to respond to a stimulus by showing physical or chemical changes in their behaviour as, for example, the delivery of the drug carried by them. The thermo-responsive nature of Pluronic® F-127 (Basf, Ludwigshafen, Germany) makes it an excellent candidate for the delivery of drugs at various application sites. In recent years, PF-127, and later, Pluronic lecithin organogels (PLO), have attracted particular interest in the design of dermal and transdermal delivery systems with a view to promoting, improving or retarding drug permeation through the skin, bearing in mind that for topical delivery systems, accumulation in the skin with minimal permeation is desired, while for systemic delivery, the opposite behaviour is preferred. In this review, we discuss the properties and characteristics of PF-127 and Pluronic lecithin organogels (PLO), and present many examples and advantages of the application of these polymeric systems in topical and transdermal administration of drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Anomalistic Self-Assembled Phase Behavior of Block Copolymer Blended with Organic Derivative Depending on Temperature

DOE PAGES

Kim, Tae-Hwan; Kim, Eunhye; Do, Changwoo; ...

2016-08-16

Amphiphilic Pluronic block copolymers have attracted great attention in a broad spectrum of potential applications due to the excellent phase behaviors in an aqueous solution, and many efforts have been made to investigate their phase behaviors under various external conditions. With a variety of external conditions, however, the closed looplike phase behaviors of a Pluronic block copolymer in an aqueous solution have not been reported yet. Herein, we report the closed looplike (CLL) phase behavior of a Pluronic P65 triblock copolymer blended with an organic derivative, 5-methylsalicylic acid (5mS), in aqueous solution, which is very unique for block copolymers. Asmore » the 5mS concentration increases, the isotropic to ordered phase or back to isotropic phase transition temperature is decreased while the number of closed loops is increased to two. To the best of our knowledge, this is the first demonstration of a CLL phase transition of a Pluronic block copolymer in an aqueous solution, which is readily applicable to optical devices such as optical sensors or optoelectronics, and nanotemplates for a highly ordered superlattice. Additionally, this provides new insight into the understanding on the phase behavior of a Pluronic block copolymer blended with additives.« less

Anomalistic Self-Assembled Phase Behavior of Block Copolymer Blended with Organic Derivative Depending on Temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Tae-Hwan; Kim, Eunhye; Do, Changwoo

Amphiphilic Pluronic block copolymers have attracted great attention in a broad spectrum of potential applications due to the excellent phase behaviors in an aqueous solution, and many efforts have been made to investigate their phase behaviors under various external conditions. With a variety of external conditions, however, the closed looplike phase behaviors of a Pluronic block copolymer in an aqueous solution have not been reported yet. Herein, we report the closed looplike (CLL) phase behavior of a Pluronic P65 triblock copolymer blended with an organic derivative, 5-methylsalicylic acid (5mS), in aqueous solution, which is very unique for block copolymers. Asmore » the 5mS concentration increases, the isotropic to ordered phase or back to isotropic phase transition temperature is decreased while the number of closed loops is increased to two. To the best of our knowledge, this is the first demonstration of a CLL phase transition of a Pluronic block copolymer in an aqueous solution, which is readily applicable to optical devices such as optical sensors or optoelectronics, and nanotemplates for a highly ordered superlattice. Additionally, this provides new insight into the understanding on the phase behavior of a Pluronic block copolymer blended with additives.« less

Evaluation of the poly(lactic-co-glycolic acid)/pluronic F127 for injection laryngoplasty in rabbits.

PubMed

Lee, Jin Ho; Kim, Dong Wook; Kim, Eun Na; Park, Seok-Won; Kim, Hee-Bok; Oh, Se Heang; Kwon, Seong Keun

2014-11-01

Poly(lactic-co-glycolic acid) (PLGA) is an aliphatic polyester and one of the most commonly used synthetic biodegradable polymers for tissue engineering. The objectives of this study were to evaluate the biocompatibility of PLGA/Pluronic F127 in the vocal fold. A randomized, prospective, controlled animal study. University laboratory. We used 18 New Zealand white rabbits, which were divided into 5% PLGA solution (n = 9) and 10% PLGA solution (n = 9) groups. The PLGA/Pluronic F127 solutions were injected into the rabbit vocal fold. Laryngoscopic exams were performed at 1, 4, and 8 weeks after implantation; then larynx specimens were sampled. High-speed video camera examination was performed for functional analysis of vocal mucosa vibration at 8 weeks after implantation. Also, we evaluated the amplitude of the mucosal wave from the laryngeal midline on high-speed recording. Histologic study of larynx specimen was performed at 4 and 8 weeks. All animals survived until the scheduled period. Laryngoscopic analysis showed that both 5% and 10% PLGA/Pluronic F127 maintained after 8 weeks after injection without significant inflammatory response. On functional analysis, high-speed camera examination revealed regular and symmetric contact of vocal fold mucosa without a distorted movement by injected PLGA/Pluronic F127. Histologically, no significant inflammation was observed in the injected vocal fold. As a vocal fold injection material, PLGA/Pluronic F127 showed a good bio-compatibility without significant inflammatory response. Further experiment will follow to elucidate its role for drug or gene delivery into the vocal fold. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.

The Effect of Pluronic 123 Surfactant concentration on The N2 Adsorption Capacity of Mesoporous Silica SBA-15: Dubinin-Astakhov Adsorption Isotherm Analysis

NASA Astrophysics Data System (ADS)

Dhaneswara, Donanta; Siti Agustina, A. A. A.; Dewantoro Adhy, P.; Delayori, Farhan; Fajar Fatriansyah, Jaka

2018-04-01

Mesoporous SBA-15 has been successfully synthesized at various concentration of Pluronic 123 surfactant (7mM, 50 mM, 54 mM, 60 mM and 66 mM) and the effect of these various concentrations on the N2 adsorption capacity has been investigated. The adsorption analysis was conducted using Dubinin-Astakhov isotherm model for multilayer adsorption phenomenon. It was found that etryat low concentration of Pluronic 123, the system exhibits type I adsorption isotherm while at high concentration, the system exhibits type IV adsorption with H1 hysteresis curve which indicates the existence of pores with cylindrical geometry, relatively uniform pore size and possibility of pore network effects. It also was found that, by using D-A isotherm model fitting, at 60 mM concentration of Pluronic 123, SBA-15 has the highest adsorption capacity which stands at 421 cm3/gram.

Effect of pH and temperature upon self-assembling process between poly(aspartic acid) and Pluronic F127.

PubMed

Nita, Loredana E; Chiriac, Aurica P; Bercea, Maria

2014-07-01

The present investigation was made in order to evaluate the capability of self-assembling of the two water soluble polymers, respectively, poly(aspartic acid) and Pluronic F127 into well interpenetrated mixture, and to evidence the connection effects intervened during polymer complex formation to exhibit good stability once formed, as well to understand and correlate the binding strength and the interval between better association domains. The effect of pH and temperature on the interpolymeric complex formation between poly(aspartic acid) and Pluronic F127 was studied by combining rheology with light scattering technique. The solution mixtures between poly(aspartic acid) and Pluronic F127 are Newtonian fluids for all ratios among them. Depending on the polymeric mixture composition and experimental temperature, positive or negative deviations of the experimental values from the additive dependence appear. An interesting behavior was registered around 1/1 wt. ratio between the two polymers, when the hydrodynamic diameter of the interpenetrated polymeric particles decreased suddenly. This allows us to conclude the formation of core-shell micelle structure with poly(aspartic acid) core and Pluronic F127 as shell, performed through strong interactions between polymers. This behavior was sustained by the increase of absolute value of zeta potential owing to the decrease of functional groups number at the surface of micelles. Copyright © 2014 Elsevier B.V. All rights reserved.

CO2 as a smart gelator for Pluronic aqueous solutions.

PubMed

Liu, Chengcheng; Mei, Qingqing; Zhang, Jianling; Kang, Xinchen; Peng, Li; Han, Buxing; Xue, Zhimin; Sang, Xinxin; Yang, Xiaogan; Wu, Zhonghua; Li, Zhihong; Mo, Guang

2014-11-25

It was found that CO2 could induce the gelation of Pluronic aqueous solutions, during which the microstructure of the solution transforms from randomly dispersed spherical micelles to cubic close packed micelles. The gelation switched by compressed CO2 has many advantages and can be applied in the synthesis of porous materials.

Effect of Pluronic F-127 on the photosensitizing activity of tetraphenylporphyrins in organic and aqueous phases

NASA Astrophysics Data System (ADS)

Savko, M. A.; Aksenova, N. A.; Akishina, A. K.; Khasanova, O. V.; Glagolev, N. N.; Rumyantseva, V. D.; Zhdanova, K. A.; Spokoinyi, A. L.; Solov'eva, A. B.

2017-11-01

The solubilization of hydrophobic porphyrin photosensitizers (PPSes) to obtain corresponding water-soluble forms is an important line of modern antimicrobial photodynamic therapy. It is shown that a triblock copolymer of ethylene and propylene oxides, Pluronic F-127, one of the most nontoxic and effective polymer surface active substances (SASes), can be used for the conversion of hydrophobic tetraphenylporphyrin (TPP) and monosubstituted and tetrasubstituted hydroxy, amino, and nitro TPPs into water-soluble forms. It is found that Pluronic has a substantially higher solubilizing affinity (defined as the minimum molar concentration of an SAS required for the complete migration of porphyrin with a specific molar concentration to the aqueous phase) toward monosubstituted TPPs than to corresponding tetrasubstituted porphyrins. It is shown that with Pluronic in the organic phase, the activity of tetraphenylporphyrin in a test reaction of the oxidation of anthracene is higher than that of its monosubstituted and tetrasubstituted derivatives. In an aqueous medium, the activity of solubilized mono derivatives of TPP is comparable to that of unsubstituted TPP and is higher than the activity of the corresponding tetra derivatives of TPP.

Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study

DOE PAGES

Ileri Ercan, Nazar; Stroeve, Pieter; Tringe, Joseph W.; ...

2016-09-13

In this paper, we investigate the interactions of Pluronics L61 and L64 with a dioleylphosphatidylcholine (DOPC) lipid bilayer by atomistic molecular dynamics simulations using the all-atom OPLS force field. Our results show that the initial configuration of the polymer with respect to the bilayer determines its final conformation within the bilayer. When the polymer is initially placed at the lipid/water interface, we observe partial insertion of the polymer in a U-shaped conformation. On the other hand, when the polymer is centered at the bilayer, it stabilizes to a transmembrane state, which facilitates water transport across the bilayer. We show thatmore » membrane thickness decreases while its fluidity increases in the presence of Pluronics. When the polymer concentration inside the bilayer is high, pore formation is initiated with L64. Finally, our results show good agreement with existing experimental data and reveal that the hydrophilic/lipophilic balance of the polymer plays a critical role in the interaction mechanisms as well as in the dynamics of Pluronics with and within the bilayer.« less

Microviscoelasticity of adhesive hard sphere dispersions: Tracer particle microrheology of aqueous Pluronic L64 solutions

NASA Astrophysics Data System (ADS)

Kloxin, Christopher J.; van Zanten, John H.

2009-10-01

DWS-based tracer particle microrheology is demonstrated to be a useful way to study the dynamics of aqueous Pluronic L64 solutions, which is viewed as a model adhesive hard sphere (AHS) system. The short-time dynamics of aqueous Pluronic L64 solutions indicate a purely hydrodynamic high frequency microviscosity as predicted by Batchelor for colloidal dispersions. The evolution of the micellar dynamics reveals a zero shear microviscosity in good agreement with steady shear viscosity measurements. As the temperature is increased, the dynamics become dominated by an apparent attractive intermicellar potential observed in microscopic creep measurements. While Pluronic L64 solutions have been reported to form a percolated micellar network, DWS-based microviscoelasticity measurements do not detect the previously observed G'˜G″˜ωΔ scaling expected for a static percolated network at low frequencies. This most likely owes to the fact that tracer particle microrheology is dominated by local Pluronic L64 micelle dynamics in the near sphere region and not the bulk mechanical properties as measured by traditional rheometry. The sensitivity of tracer particle microrheological measurements to the true dynamic nature of the percolated network in weak physical gels highlights the distinct differences between these micro- and macrorheology measurement techniques. Such discrepancies should be most evident in systems that are dominated by association processes such as those occurring in AHS solutions or polymer solutions approaching a phase boundary. Despite this, the AHS potential is qualitatively consistent with the results found here.

Microviscoelasticity of adhesive hard sphere dispersions: tracer particle microrheology of aqueous Pluronic L64 solutions.

PubMed

Kloxin, Christopher J; van Zanten, John H

2009-10-07

DWS-based tracer particle microrheology is demonstrated to be a useful way to study the dynamics of aqueous Pluronic L64 solutions, which is viewed as a model adhesive hard sphere (AHS) system. The short-time dynamics of aqueous Pluronic L64 solutions indicate a purely hydrodynamic high frequency microviscosity as predicted by Batchelor for colloidal dispersions. The evolution of the micellar dynamics reveals a zero shear microviscosity in good agreement with steady shear viscosity measurements. As the temperature is increased, the dynamics become dominated by an apparent attractive intermicellar potential observed in microscopic creep measurements. While Pluronic L64 solutions have been reported to form a percolated micellar network, DWS-based microviscoelasticity measurements do not detect the previously observed G(') approximately G(") approximately omega(Delta) scaling expected for a static percolated network at low frequencies. This most likely owes to the fact that tracer particle microrheology is dominated by local Pluronic L64 micelle dynamics in the near sphere region and not the bulk mechanical properties as measured by traditional rheometry. The sensitivity of tracer particle microrheological measurements to the true dynamic nature of the percolated network in weak physical gels highlights the distinct differences between these micro- and macrorheology measurement techniques. Such discrepancies should be most evident in systems that are dominated by association processes such as those occurring in AHS solutions or polymer solutions approaching a phase boundary. Despite this, the AHS potential is qualitatively consistent with the results found here.

Surfactant selection for a liquid foam-bed photobioreactor.

PubMed

Janoska, Agnes; Vázquez, María; Janssen, Marcel; Wijffels, René H; Cuaresma, María; Vílchez, Carlos

2018-02-01

A novel liquid foam-bed photobioreactor has been shown to hold potential as an innovative technology for microalgae production. In this study, a foam stabilizing agent has been selected which fits the requirements of use in a liquid foam-bed photobioreactor. Four criteria were used for an optimal surfactant: the surfactant should have good foaming properties, should not be rapidly biodegradable, should drag up microalgae in the foam formed, and it should not be toxic for microalgae. Ten different surfactants (nonionic, cationic, and anionic) and two microalgae genera (Chlorella and Scenedesmus) were compared on the above-mentioned criteria. The comparison showed the following facts. Firstly, poloxameric surfactants (Pluronic F68 and Pluronic P84) have acceptable foaming properties described by intermediate foam stability and liquid holdup and small bubble size. Secondly, the natural surfactants (BSA and Saponin) and Tween 20 were easily biodegraded by bacteria within 3 days. Thirdly, for all surfactants tested the microalgae concentration is reduced in the foam phase compared to the liquid phase with exception of the cationic surfactant CTAB. Lastly, only BSA, Saponin, Tween 20, and the two Pluronics were not toxic at concentrations of 10 CMC or higher. The findings of this study indicate that the Pluronics (F68 and P84) are the best surfactants regarding the above-mentioned criteria. Since Pluronic F68 performed slightly better, this surfactant is recommended for application in a liquid foam-bed photobioreactor. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

PubMed Central

Fan, Wei; Wu, Xin; Ding, Baoyue; Gao, Jing; Cai, Zhen; Zhang, Wei; Yin, Dongfeng; Wang, Xiang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2012-01-01

Background Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers’ structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake. Methods This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers. Results Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus. Conclusion This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future. PMID:22403492

Evaluation of the Effect of a Gamma Irradiated DBM-Pluronic F127 Composite on Bone Regeneration in Wistar Rat

PubMed Central

Canciani, Barbara; Losi, Paola; Tripodi, Maria; Burchielli, Silvia; Ottoni, Priscilla; Salvadori, Piero Antonio; Soldani, Giorgio

2015-01-01

Demineralized bone matrix (DBM) is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs) amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127) composite implanted in the femur of rats. Gamma irradiation effects (25 kGy) on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w) of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability. PMID:25897753

Preparation and anti-bacterial properties of a temperature sensitive gel containing silver nanoparticles

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to prepare a novel temperature-sensitive spray gel containing silver nanoparticles and investigate its anti-bacterial properties in vitro. Methods: The aqueous complex gel was prepared by Pluronic F127 (18-22%) and Pluronic F68 (3-9%) through a cold method to obtain a p...

Growth and shrinkage of pluronic micelles by uptake and release of flurbiprofen: variation of pH.

PubMed

Alexander, Shirin; de Vos, Wiebe M; Castle, Thomas C; Cosgrove, Terence; Prescott, Stuart W

2012-04-24

The micellization of Pluronic triblock copolymers (P103, P123, and L43) in the presence of flurbiprofen at different pH was studied by small-angle neutron scattering (SANS), pulsed-field gradient stimulated-echo nuclear magnetic resonance (PFGSE-NMR), and surface tension measurements. Addition of flurbiprofen to the Pluronic at low pH leads to an increase in the fraction of micellization, aggregation number, and the core radius of the micelles. However, changing the pH to above the pKa of flurbiprofen in an ethanol/water mixture (∼6.5) reduces the fraction of micellization and results in a weaker interaction between the drug and micelles due to the increased drug solubility in aqueous solution.

Physiochemical Characterization and Release Rate Studies of SolidDispersions of Ketoconazole with Pluronic F127 and PVP K-30

PubMed Central

Kumar, Pankaj; Mohan, Chander; KanamSrinivasan Uma Shankar, Mara; Gulati, Monica

2011-01-01

In the present study solid dispersions of the antifungal drug Ketoconazole were prepared with Pluronic F-127 and PVP K-30 with an intention to improve its dissolution properties. Investigations of the properties of the dispersions were performed using release studies, Differential scanning calorimetery (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR). The results obtained showed that the rate of dissolution of Ketoconazole was considerably improved when formulated in solid dispersions with PVP K-30 and Pluronic F-127 as compared with pure drug and physical mixtures. The results from DSC and XRD studies showed the transition of crystalline nature of drug to amorphous form, while FTIR studies demonstrated the absence of drug-carriers interaction. PMID:24250403

Sodium deoxycholate mediated enhanced solubilization and stability of hydrophobic drug Clozapine in pluronic micelles

NASA Astrophysics Data System (ADS)

Singla, Pankaj; Singh, Onkar; Chabba, Shruti; Aswal, V. K.; Mahajan, Rakesh Kumar

2018-02-01

In this report, the solubilization behaviour of a hydrophobic drug Clozapine (CLZ) in micellar suspensions of pluronics having different hydrophilic lipophilic balance (HLB) ratios viz. P84, F127 and F108 in the absence and presence of bile salt sodium deoxycholate (SDC) has been studied. UV-Vis spectroscopy has been exploited to determine the solubilization capacity of the investigated micellar systems in terms of drug loading efficiency, average number of drug molecules solubilized per micelle (ns), partition coefficient (P) and standard free energy of solubilization (Δ G°). The morphological and structural changes taking place in pluronics in different concentration regimes of SDC and with the addition of drug CLZ has been explored using dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The SANS results revealed that aggregation behaviour of pluronic-SDC mixed micelles gets improved in the presence of drug. The micropolarity measurements have been performed to shed light on the locus of solubilization of the drug in pure and mixed micellar systems. The compatibility between CLZ and drug carriers (pluronics and SDC) was confirmed using powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) techniques. Among the investigated systems, P84-SDC mixed system was found to be highly efficient for CLZ loading. The long term stability data indicated that CLZ loaded P84-SDC mixed micellar formulation remained stable for 3 months at room temperature. Further, it was revealed that the CLZ loaded P84-SDC mixed micelles are converted into CLZ loaded pure P84 micelles at 30-fold dilutions which remain stable up to 48-fold dilutions. The results from the present studies suggest that P84-SDC mixed micelles can serve as suitable delivery vehicles for hydrophobic drug CLZ.

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

PubMed

Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

2015-12-07

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

[Subchondral drilling method combined with gum-bletilla complex to repair articular cartilage defects].

PubMed

Huang, Yong; Wang, Xin-Ling; Qiu, Heng; Xiao, Yi-Cheng; Wu, Zong-Hong; Xu, Jian

2018-02-01

Two types(A model and B model) of articular cartilage defect models were prepared by using adult New Zealand white rabbits. A model group was applied by drilling without through subchondral bone, whose right joint was repaired by composite scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left side was blank control. B model group was applied by subchondral drilling method, whose right joint was repaired by using composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cells, and left side was blank control. Autogenous contrast was used in both model types. In addition, another group was applied with B model type rabbits, which was repaired with artificial complex material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after operation, the animals were sacrificed and the samples were collected from repaired area for staining with HE, typeⅡcollagen immunohistochemical method, Alcian blue, and toluidine blue, and then were observed with optical microscope. Semi-quantitative scores were graded by referring to Wakitanis histological scoring standard to investigate the histomorphology of repaired tissue. Hyaline cartilage repairing was achieved in both Group A and Group B, with satisfactory results. There were no significant differences on repairing effects for articular cartilage defects between composite scaffolds made by seed cell, gum-bletilla and Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cell. Better repairing effects for articular cartilage defects were observed in groups with use of gum-bletilla, indicating that gum-bletilla is a vital part in composite scaffolds material. Copyright© by the Chinese Pharmaceutical Association.

Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery.

PubMed

Abd-Elsalam, Wessam H; El-Zahaby, Sally A; Al-Mahallawi, Abdulaziz M

2018-11-01

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 2 3 full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98 ± 0.40%) and a very small micellar size (33.23 ± 8.00 nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.

Cubosome formulations stabilized by a dansyl-conjugated block copolymer for possible nanomedicine applications.

PubMed

Murgia, Sergio; Falchi, Angela Maria; Meli, Valeria; Schillén, Karin; Lippolis, Vito; Monduzzi, Maura; Rosa, Antonella; Schmidt, Judith; Talmon, Yeshayahu; Bizzarri, Ranieri; Caltagirone, Claudia

2015-05-01

We present here an innovative, fluorescent, monoolein-based cubosome dispersion. Rather than embedded within the monoolein palisade, the fluorescent imaging agent, namely dansyl, was conjugated to the terminal ethylene oxide moieties of the block copolymer Pluronic F108. We discuss the physicochemical and photophysical properties of this fluorescent Pluronic and of a cubosome formulation stabilized by a mixture of dansyl-conjugated and non-conjugated Pluronic, also including an anticancer drug (quercetin). Furthermore, we performed biocompatibility tests against HeLa cells to assess internalization and cytotoxicity features of this nanoparticles aqueous dispersion. Cryo-TEM, SAXS, and DLS analysis, proved the bicontinuous cubic inner nanostructure and the morphology of this fluorescent cubosome dispersion, while photophysical measurements and biocompatibility results basically validate their potential use for theranostic nanomedicine applications. Copyright © 2015 Elsevier B.V. All rights reserved.

The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system.

PubMed

Zhang, Zhenhai; Cui, Changchang; Wei, Fang; Lv, Huixia

2017-08-01

The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus ® and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5 nm) and spherical shape at ratio of 4:1 (Soluplus ® :Pluronic F127), as well as increasing solubility of to 5.61 mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72 and 5.32%, respectively, and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus ® and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.

Block ionomer complexes as prospective nanocontainers for drug delivery.

PubMed

Oh, Kyung T; Bronich, Tatiana K; Bromberg, Lev; Hatton, T Alan; Kabanov, Alexander V

2006-09-28

Nanosized environmentally responsive materials are of special interest for various applications, including drug delivery. Block ionomer complexes (BIC) composed of graft-comb copolymers of Pluronic and poly(acrylic acid) (Pluronic-PAA) and a model cationic surfactant, hexadecyltrimethylammonium bromide (HTAB), were synthesized by mixing the polymer and surfactant in aqueous media. According to TEM, the resulting BIC represented spherical particles of nanoscale size (50 to 100 nm). The stability of the BIC in the aqueous dispersion depended on the lengths of the hydrophilic poly(ethylene oxide) and hydrophobic poly(propylene oxide) chains in Pluronic molecules as well as on the surface charge of the resulting complexes. The latter was controlled by changing the ratio of the Pluronic-PAA and HTAB in the BIC and by changing the pH due to reversible ionization of the PAA chains. The acidification of the media below pH 6.0 resulted in the appearance of a strong positive charge on the BIC, which in the intracellular environment can trigger interaction of such BIC with the cell membranes. An efficient solubilization of a model hydrophobic molecule, Sudan III, and a drug, Etoposide, in such BIC was demonstrated with the loading capacities of about 6 to 15% by weight of the dispersed complex. Overall, these BIC wield a promise as environmentally responsive nanocarriers for pharmaceuticals.

Synthesis and Catalytic Activity of Pluronic Stabilized Silver-Gold Bimetallic Nanoparticles.

PubMed

Holden, Megan S; Nick, Kevin E; Hall, Mia; Milligan, Jamie R; Chen, Qiao; Perry, Christopher C

2014-01-01

In this report, we demonstrate a rapid, simple, and green method for synthesizing silver-gold (Ag-Au) bimetallic nanoparticles (BNPs). We used a novel modification to the galvanic replacement reaction by suspending maltose coated silver nanoparticles (NPs) in ≈ 2% aqueous solution of EO 100 PO 65 EO 100 (Pluronic F127) prior to HAuCl 4 addition. The Pluronic F127 stabilizes the BNPs, imparts biocompatibility, and mitigates the toxicity issues associated with other surfactant stabilizers. BNPs with higher Au:Ag ratios and, subsequently, different morphologies were successfully synthesized by increasing the concentration of gold salt added to the Ag NP seeds. These BNPs have enhanced catalytic activities than typically reported for monometallic Au or Ag NPs (∼ 2-10 fold) of comparable sizes in the sodium borohydride reduction of 4-nitrophenol. The 4-nitrophenol reduction rates were highest for partially hollow BNP morphologies.

Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

NASA Astrophysics Data System (ADS)

Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

2016-06-01

Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.

Magnetic nanoparticles for bio-analytical applications

NASA Astrophysics Data System (ADS)

Yedlapalli, Sri Lakshmi

Magnetic nanoparticles are widely being used in various fields of medicine, biology and separations. This dissertation focuses on the synthesis and use of magnetic nanoparticles for targeted drug delivery and analytical separations. The goals of this research include synthesis of biocompatible surface modified monodisperse superparamagnetic iron oxide nanoparticles (SPIONs) by novel techniques for targeted drug delivery and use of SPIONs as analytical sensing tools. Surface modification of SPIONs was performed with two different co-polymers: tri block co-polymer Pluronics and octylamine modified polyacrylic acid. Samples of SPIONs were subsequently modified with 4 different commercially available, FDA approved tri-block copolymers (Pluronics), covering a wide range of molecular weights (5.75-14.6 kDa). A novel, technically simpler and faster phase transfer approach was developed to surface modify the SPIONs with Pluronics for drug delivery and other biomedical applications. The hydrodynamic diameter and aggregation properties of the Pluronic modified SPIONs were studied by dynamic light scattering (DLS). The coverage of SPIONs with Pluronics was supported with IR Spectroscopy and characterized by Thermo gravimetric Analysis (TGA). The drug entrapment capacity of SPIONs was studied by UV-VIS spectroscopy using a hydrophobic carbocyanine dye, which serves as a model for hydrophobic drugs. These studies resulted in a comparison of physical properties and their implications for drug loading capacities of the four types of Pluronic coated SPIONs for drug delivery assessment. These drug delivery systems could be used for passive drug targeting. However, Pluronics lack the functional group necessary for bioconjugation and hence cannot achieve active targeting. SPIONs were functionalized with octylamine modified polyacrylic acid-based copolymer, providing water solubility and facile biomolecular conjugation. Epirubicin was loaded onto SPIONs and the drug entrapment was studied by UVVIS spectrophotometry. In this study, the antisense oligonucleotide sequence to the anti-apoptopic protein survivin was coupled to SPIONs to provide molecular targeting and potential therapy for cancer cells. Successful coupling of antisense survivin to SPIONs was demonstrated by circular dichroism studies of the conjugate and its complementary sequence. Such multifunctional SPIONs can be used as active targeting agents for cancer cells, producing enhanced magnetic resonance imaging contrast and releasing chemotherapeutic agents to targeted cells. SPIONs also serve as an excellent platform for analytical sensing. Streptavidin modified SPIONs were used as substrates to immobilize biotinylated aptamers (single-stranded DNA). The binding affinity of such aptamers to its target was achieved by quantifying the amount of target released from the aptamer. This quantification was achieved using pH-mediated stacking capillary electrophoresis. SPIONs were shown to be more efficient compared to magnetic microbeads as the sensing elements. The binding affinity constant of the aptamer determined was almost 8-fold better than that obtained using magnetic microbeads.

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.

PubMed

Andrade, Fernanda; das Neves, José; Gener, Petra; Schwartz, Simó; Ferreira, Domingos; Oliva, Mireia; Sarmento, Bruno

2015-10-01

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Co-micellized Pluronic mixture with thermo-sensitivity and residence stability as an injectable tissue adhesion barrier hydrogel.

PubMed

Oh, Se Heang; Kang, Jun Goo; Lee, Jin Ho

2018-01-01

Although the tissue adhesion which leads to various complications frequently occurs after surgery, the development of an ideal tissue adhesion barrier is still a challenge. In this study, a thermo-sensitive hydrogel, which can fulfill the essential requirements of tissue adhesion barrier (that is, ease of handling for surgeon, flowing down prevention after application, stable residence on the injury during wound healing, and no use of toxic additives), was developed using biocompatible polyethylene glycol-polypropylene glycol copolymers (Pluronic F127/F68/P123 mixture). From the in vitro cell culture and in vivo animal study, it was observed that the Pluronic mixtures showed sol-gel transition at approximately body temperature (for easy injection or coating on the injury site and flowing down prevention after application) and prolonged residence stability in aqueous environment (> ∼7 days for stable protection of injury tissues/organs during wound healing), and thus was highly effective for the prevention of tissue adhesion without adverse tissue responses. Based on these results, the Pluronic F127/F68/P123 mixture itself (without any additives) can be a good candidate as an injectable or coatable tissue adhesion barrier hydrogel applicable to various injury tissues in terms of ease of use, effectiveness, and safety. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 172-182, 2018. © 2016 Wiley Periodicals, Inc.

Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation.

PubMed

Parhi, Rabinarayan; Suresh, Podilam; Pattnaik, Subasini

2016-06-01

In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p < 0.05), whereas the influences of different concentrations of pluronic were insignificant. The effect of different solvents/penetration enhancers viz. IPM, propylene glycol (PG), dimethyl sulphoxide (DMSO), and D-limonene, in combination and alone, on the permeation of DZH across the dorsal skin of rat was studied. Among all, formulation containing IPM (PLO6) exhibited highest flux of 147.317 μg/cm(2)/h. Furthermore, histopathology section of treated skin sample illustrated that lipid bilayer disruption was the mechanism for the DZH permeation. The above results indicated that PLO6 may serve as a promising alternative delivery system for DZH in the effective treatment of hypertension.

Dispersant affects the cellular influences of single-wall carbon nanotube: the role of CNT as carrier of dispersants.

PubMed

Horie, Masanori; Stowe, Mayumi; Tabei, Miki; Kato, Haruhisa; Nakamura, Ayako; Endoh, Shigehisa; Morimoto, Yasuo; Fujita, Katsuhide

2013-06-01

The application of carbon nanotube (CNT) as a functional material to engineering and life sciences is advanced. In order to evaluate the cytotoxicity of CNT in vitro, some chemical and biological reagents are used for dispersants. In the present study, the cellular influences of six kinds of chemical or biological reagents used as dispersants were examined. Pluronic F-127, Pluronic F-68, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), pulmonary surfactant preparation Surfacten®, bovine serum albumin (BSA) and Tween 80 were used in the preparation of CNT-medium dispersants. The influences of each reagent on cell viability in human lung carcinoma A549 cells were small. However, Pluronic F-127, DPPC, Surfacten® and Tween 80 induced an increase of intracellular reactive oxygen species (ROS) level. Next, CNT-medium dispersions were prepared, using each reagent as a dispersant and applied to A549 cells. The cellular influences depended on the kind of dispersant. Cells exposed to CNT dispersion including Pluronic® F-127, Surfacten®, DPPC and Tween 80 showed LDH release to the culture supernatant. Induction of intracellular ROS level was observed in cells exposed to CNT dispersion including each reagent except BSA. These results suggest that the adsorbed dispersant reagents on the surface of the CNT affect its cellular influences, particularly the induction of oxidative stress.

Bulk and dispersed aqueous behaviour of an endogenous lipid, selachyl alcohol: Effect of Tween 80 and Pluronic F127 on nanostructure.

PubMed

Younus, Mohammad; Hawley, Adrian; Boyd, Ben J; Rizwan, Shakila B

2018-05-07

Tween 80 has been reported to provide a means of targeting drug nanocarriers to the blood- brain barrier. This study investigated the influence of addition of Tween 80 on the formation of different bulk and dispersed lyotropic liquid crystalline phases in selachyl alcohol-based systems. The effect of increasing concentrations of Tween 80 and Pluronic F127 (as a control) (0-25% w/w relative to SA) on the bulk phase behaviour and dispersions of selachyl alcohol (SA) were investigated using small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. The addition of Tween 80 to SA bulk phase samples triggered concentration-dependent phase changes with the structure sequentially evolving from a reverse hexagonal phase (H 2 ) to a mixed H 2 and inverse bicontinuous cubic (V 2 ) then a V 2 phase alone. In contrast, the addition of Pluronic F127 resulted in a phase change from H 2 phase to a mixed lamellar and H 2 phase system. The mean particle size of internally structured particles was 125-190 nm with low polydispersity indices (0.1-0.2). Nanoparticles retained the bulk phase internal structure in the presence of Tween 80, whereas in the presence of Pluronic F127, the additional lamellar phase that formed in bulk phase systems was not observed. Cryo-TEM revealed the formation of cubosomes and hexosomes by SA in excess water in the presence of Tween 80 and Pluronic F127 respectively. In summary, it was shown that stabilisation of SA dispersions using Tween 80 resulted in a decrease in negative curvature leading to a change in internal structure from H 2 to V 2 phase. The studies provide the core understanding of particle structure to progress these structured lipid nanocarriers into delivery studies with Tween 80 as a mechanism to target the blood-brain barrier. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

A novel in-situ-gelling liquid suppository for site-targeting delivery of anti-colorectal cancer drugs.

PubMed

Lin, Hong-Ru; Tseng, Chao-Chih; Lin, Yiu-Jiuan; Ling, Ming-Hung

2012-01-01

In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic-poly(acrylic acid) (Pluronic-PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0→12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.

Nafion as Cosurfactant: Solubilization of Nafion in Water in the Presence of Pluronics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelarakis, Antonios; Giannelis, Emmanuel P.

2011-01-18

Incorporation of Nafion to aqueous solutions of Pluronics adversely impacts micellization due to extensive Nafion/copolymer interactions. Light scattering and zeta potential measurements provide evidence for the formation of sizable and stable Nafion/copolymer complexes, in expense of the neat copolymer micelles. At high copolymer concentrations, the overall interaction diagram of Nafion/copolymer reflects the competitive action of the release of packing constraints due to micellar destabilization induced by Nafion on one hand and the gelator nature of the Nafion on the other. Measurements using a quartz crystal microbalance (QCM-D) show that aqueous solutions of Pluronics (even at very low concentration) can dissolvemore » the Nafion coating on the crystal resonator, while typical low molecular weight ionic surfactants fail to induce similar effects. These studies demonstrate that complexation with this class of copolymers is a facile route to impart dispersibility to Nafion in aqueous environments that otherwise can be achieved through tedious and harsh treatments.« less

Molecular Dynamics Simulations of Cubic Phases in Pluronics Systems and Their Role in Templating Nanoparticles

NASA Astrophysics Data System (ADS)

Anderson, Joshua; Travesset, Alex; Lorenz, Chris

2007-03-01

We discuss molecular dynamics simulations aimed at predicting phase diagrams in Pluronic systems. Crystalline phases with cubic symmetries are particularly challenging to simulate. A general method that is able to obtain these phases is presented. As an example, we show our results for a system of ABA triblock polymers where each hydrophilic A block contains 10 beads and the hydrophobic block B contains 7 beads. These values match the ratio of PEO to PPO in Pluronic F127. Numerous simulation runs are carried out with differing initial conditions, which consistently produce textbook bcc and fcc lattices of micelles along with two other distorted bcc lattices. We find that the formation of a lattice is sensitive to the system's preparation and depends mainly on the kinetic temperature and equilibration time. Examination of the distorted lattices shows that they are related to the finite size of the simulation box. We conclude with some discussion on using these crystals as a template for nanoparticles or biomineralization.

Periadventitial Application of Rapamycin-Loaded Nanoparticles Produces Sustained Inhibition of Vascular Restenosis

PubMed Central

Guo, Lian-Wang; Si, Yi; Zhu, Men; Pilla, Srikanth; Liu, Bo; Gong, Shaoqin; Kent, K. Craig

2014-01-01

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. PMID:24586612

Optical limiting in Pluronic F-127 hydrogel with nanocarbon inclusions

NASA Astrophysics Data System (ADS)

Nikolaeva, A. L.; Povarov, S. A.; Bocharov, V. N.

2017-02-01

Characteristics of nonlinear optical limiting (limiting curves) of laser radiation in aqueous polymer systems with nanocarbon inclusions have been studied. Suspensions of nanotubes and soot stabilized by the amphiphilic polymer Pluronic F-127, the additives of which provide the system's transition to a solid-like hydrogel aggregate state at room temperature, have been considered. The limiting materials after their optical breakdown by high-intensity radiation in the gel state have been regenerated using the thermoreversible hydrogel-isotropic solution phase transition. These systems are shown to be promising for self-healing optical materials.

Preparation of alpha-cyclodextrin-terminated polyrotaxane consisting of beta-cyclodextrins and pluronic as a building block of a biodegradable network.

PubMed

Ooya, Tooru; Ito, Akihiro; Yui, Nobuhiko

2005-05-23

A beta-CD-based biodegradable polyrotaxane was prepared by capping both terminals of polypseudorotaxane consisting of hydrazide-terminated PEG-block-PPG-block-PEG (Pluronic P-105) and beta-CD-succinates with mono-aldehyde alpha-CDs. By decreasing pH, the fluorescent intensity of TNS was increased with time, indicating cleavage of the terminal hydrazone bonds followed by beta-CD-succinate release. The terminal alpha-CD moieties of the polyrotaxane are useful for self-assembled formation with some guest molecules. [Diagram: see text

Pluronic lecithin organogel as a topical drug delivery system.

PubMed

Pandey, Mohit; Belgamwar, Veena; Gattani, Surendra; Surana, Sanjay; Tekade, Avinash

2010-01-01

The objective of this study was to formulate and evaluate the pluronic lecithin organogel containing flurbiprofen for topical application. Different formulations of pluronic lecithin organogels were prepared by using pluronic F127, lecithin, flurbiprofen, isopropyl palmitate, water, sorbic acid, and potassium sorbate. To study the in vitro potential of these formulations, permeation studies were performed with Keshary-Chien diffusion cells. The results of the in vitro permeation studies found that release of flurbiprofen from dialysis membrane-70 was more than excised dorsal rat skin. Gelation temperature study was carried out to determine the temperature where sol-gel transformation takes place. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°C, the viscosity of formulations increases as the lecithin concentration increases. Also the formulations were tested for appearance and feel psychorheologically, pH, and drug content. Interactions between the components of the gel have been investigated by differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation subjected to differential scanning calorimetry shows no drug-polymer interaction. To investigate the in vivo performance of the formulations, a carrageenan-induced rat paw edema model and skin irritation study was used. The stability studies and freeze-thaw thermal cyclic test were carried out, showing no phase separation of gel, and representing gel stability. Statistical analysis of the data of animal study (anti-inflammatory activity) was done by using one way analysis of variance (ANOVA) followed by Dunnett's test. The formulation shows a statistically significant anti-inflammatory activity and is non-irritant to skin.

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid.

PubMed

Dalpiaz, Alessandro; Contado, Catia; Mari, Lara; Perrone, Daniela; Pavan, Barbara; Paganetto, Guglielmo; Hanuskovà, Miriam; Vighi, Eleonora; Leo, Eliana

2014-05-01

Zidovudine (AZT) is employed against AIDS and hepatitis; its use is limited by active efflux transporters (AETs) that induce multidrug resistance for intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid (UDCA) conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems. To investigate the effect of the Pluronic F68 coating on the loading, release and stability of poly(D,L lactide-co-glicolide) nanoparticles (NPs) embedded with UDCA-AZT. The mean diameter of the NP prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field-flow fractionation; particle morphology was detected by scanning electron microscope. The stability of the free and encapsulated UDCA-AZT was evaluated in rat liver homogenates by high-performance liquid chromatography analysis. The mean diameter of the NPs was found to be ∼ 600 nm with a relatively high polydispersity. The NPs obtained by emulsion/solvent evaporation were not able to control the prodrug release, differently from NPs obtained by nanoprecipitation. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release, or the extent of the burst effect that were instead only influenced by the preparation parameters. UDCA-AZT incorporated in the NPs was more stable in the rat liver homogenates than the free prodrug and no influence of the Pluronic coating was observed. Considering the different potential applications of nanoparticles coated and uncoated with Pluronic (brain and macrophage targeting, respectively), both of these nanoparticle systems could be useful in the therapies against HIV.

Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and cinnamic acid-Pluronic F127 conjugate.

PubMed

Zhang, Hong; Kim, Jin-Chul

2016-01-01

Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.

Novel bioprinting method using a pectin based bioink.

PubMed

Banks, Amanda; Guo, Xiaoru; Chen, Junhong; Kumpaty, Subha; Zhang, Wujie

2017-08-09

One major challenge of bioprinting is to develop a viable bioink to act as an extracellular matrix. This study investigated a novel method for bioprinting using a pectin based bioink. Besides pectin, Pluronic® F-127 was incorporated into the bioink to obtain the desired shape during the initial bioprinting process at 37∘C. Once an object was printed it was treated with Ca2+ (pectin cross-linker) to create the final tissue/organ structure. The results indicated that pectin/Pluronic® F-127 is a potential bioink. Moreover, this methodology provides a novel and fast approach for bioprinting.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

PubMed

Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

2016-11-01

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

Transport across the blood-brain barrier of pluronic leptin.

PubMed

Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V

2010-04-01

Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p < 0.0005; 0-2 h, p < 0.001]. These studies show that the structure based Pluronic modification of leptin increased metabolic stability, reduced food intake, and allowed BBB penetration by a mechanism-independent BBB leptin transporter.

In vivo comparison of various polymeric and low molecular mass inhibitors of intestinal P-glycoprotein.

PubMed

Föger, Florian; Hoyer, Herbert; Kafedjiiski, Krum; Thaurer, Michael; Bernkop-Schnürch, Andreas

2006-12-01

Several polymers have been reported to modulate drug absorption by inhibition of intestinal P-glycoprotein (P-gp). The aim of the present study was to provide a direct in vivo comparison of delivery systems based on Pluronic P85, Myrj 52 and chitosan-4-thiobutylamidine (Ch-TBA) in vivo in rats, using rhodamine-123 (Rho-123) as representative P-gp substrate. Furthermore, the postulated low molecular mass P-gp inhibitors 6-mercaptopurine and reduced glutathione (GSH) were evaluated in vitro and in vivo. In vitro, the permeation enhancing effect of 6-mercaptopurine, GSH, Pluronic P85, Myrj 52, and the combination of Ch-TBA with GSH was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type diffusion chambers. In comparison to buffer only, Rho-123 transport in presence of 100 microm 6-mercaptopurine, 0.5% (w/v) GSH, 0.5% (w/v) Pluronic P85, 0.5% (w/v) Myrj 52 and the combination of 0.5% (w/v) Ch-TBA/ 0.5% (w/v) GSH, was 2.1, 1.6, 1.9, 1.8, 3.0-fold improved, respectively. In vivo in rat, enteric-coated tablets based on Pluronic P85, Myrj 52 or Ch-TBA/GSH increased the area under the plasma concentration time curve (AUC(0-12)) of Rho-123 1.6-fold, 2.4-fold, 4.3-fold, respectively, in comparison to control only. Contrariwise, the low molecular mass excipients 6-mercaptopurine and GSH showed no significant effect in vivo at all. This in vivo study showed that polymeric P-gp inhibitors and especially the delivery system based on thiolated chitosan significantly increased the oral bioavailability of P-gp substrate Rho-123.

Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies.

PubMed

Wei, Gang; Xu, Hui; Ding, Ping Tian; Li, San Ming; Zheng, Jun Min

2002-09-18

For ophthalmic drug delivery, Pluronic F127 solutions have a phase transition temperature too low for them to be instilled into the eye at room temperature. Refrigerator storage is usually required to make administration easier, whereas the potential irritation of cold to the sensitive ocular tissues may result in poor topical bioavailability. The purpose of this study is to develop a thermosetting gel with a suitable phase transition temperature by combining Pluronic analogs and to examine the influence of incorporating mucoadhesive polysaccharide, sodium hyaluronate (HA-Na), on the ocular retention of the gel. Dynamic rheological method and single photon emission computing tomography (SPECT) technique were used to ex/in vivo evaluate the thermosetting gels, respectively. An optimized formulation containing 21% F127 and 10% F68 increased the phase transition temperature by 9 degrees C as evaluated by elasticity modulus compared to that of individual 21% F127 solution. Rheological behaviors of the Pluronic solutions showed that the combined Pluronic formulation was free flowing liquid below 25 degrees C and converted to a firm gel under the physiological condition. Furthermore, this formulation possessed the highest viscosity both before and after tear dilution at 35 degrees C. Gamma scintigraphic data demonstrated that the clearance of the thermosetting gel labeled with 99mTc-DTPA was significantly delayed with respect to the phosphate buffered solution, and at least a threefold increase of the corneal residence time was achieved. However, no further improvement in the ocular retention was observed when adding HA-Na into the thermosetting gel due to the substantially decreased gel strength. Copyright 2002 Elsevier Science B.V.

Effect of a Pluronic(®) P123 formulation on the nitric oxide-generating drug JS-K.

PubMed

Kaur, Imit; Kosak, Ken M; Terrazas, Moises; Herron, James N; Kern, Steven E; Boucher, Kenneth M; Shami, Paul J

2015-04-01

O(2)-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare Pluronic(®) P123-formulated JS-K (P123/JS-K) with free JS-K. We determined micelle size, shape, and critical micelle concentration of Pluronic(®) P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenograft in NOD/SCID IL2Rγ (null) mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2Rγ (null) mice when compared to free JS-K-treated NOD/SCID IL2Rγ (null) mice. Pluronic(®) P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K.

Thermo-Osmotic Flow in Thin Films.

PubMed

Bregulla, Andreas P; Würger, Alois; Günther, Katrin; Mertig, Michael; Cichos, Frank

2016-05-06

We report on the first microscale observation of the velocity field imposed by a nonuniform heat content along the solid-liquid boundary. We determine both radial and vertical velocity components of this thermo-osmotic flow field by tracking single tracer nanoparticles. The measured flow profiles are compared to an approximate analytical theory and to numerical calculations. From the measured slip velocity we deduce the thermo-osmotic coefficient for both bare glass and Pluronic F-127 covered surfaces. The value for Pluronic F-127 agrees well with Soret data for polyethylene glycol, whereas that for glass differs from literature values and indicates the complex boundary layer thermodynamics of glass-water interfaces.

Sulfur-carbon nanocomposite cathodes improved by an amphiphilic block copolymer for high-rate lithium-sulfur batteries.

PubMed

Fu, Yongzhu; Su, Yu-Sheng; Manthiram, Arumugam

2012-11-01

A sulfur-carbon nanocomposite consisting of a commercial high-surface-area carbon (i.e., Black Pearls 2000, BET surface area >1000 m² g⁻¹) and sulfur has been synthesized by an in situ deposition method. The nanocomposite is in the form of agglomerated nanoparticles, with the micropores within the carbon filled with sulfur and the mesopores on the carbon surface almost completely covered by sulfur. The BET surface area of the nanocomposite containing a sulfur content of 63.5 wt % is significantly reduced to only 40 m² g⁻¹. Cathodes containing the nanocomposite and Pluronic F-127 block copolymer, which partially replaces the polyvinylidene fluoride binder, were prepared and evaluated in lithium cells by cyclic voltammetry and galvanostatic cycling. The nanocomposite cathodes with the copolymer show improved electrochemical stability and cyclability. The Pluronic copolymer helps retain a uniform nanocomposite structure within the electrodes, improving the electrochemical contact, which was manifested by scanning electron microscopy and electrochemical impedance spectroscopy. The sulfur-Black Pearls nanocomposite with the Pluronic copolymer as an additive in the electrodes is promising for high-rate rechargeable lithium-sulfur batteries.

The conformation of Pluronic block copolymers adsorbed on carbon nanotubes and their interaction with water studied by small-angle neutron scattering

NASA Astrophysics Data System (ADS)

Cohen, Yachin; Granite, Meirav; Pyckhout-Hintzen, Wim; Radulescu, Aurel

2010-03-01

Amphiphilic block copolymers are particularly useful in dispersing single-walled carbon nanotubes (SWCNT) in water. Small-angle neutron scattering measurements conducted at different D2O/H2O content of the dispersing medium provide quantitative information on the adsorption density and conformation of the polymer interacting with the nanotube surface. Data is presented on Pluronic F108 - (EO)132(PO)50(EO)132 and F127 (EO)100(PO)65(EO)100, where EO-ethylene oxide and PO-propylene oxide, well below the critical micellization temperature of the polymer. A dense coating of the PPO blocks on the nanotube surface is determined with the PEO chains extended from the cylindrical core-shell structure. The data from the two Pluronic systems show minimal scattering at about 70% D2O in the dispersing water, which exhibit a q -1 power law of the scattering vector (q ). This indicates near matching of the polymer chains at a surprisingly high scattering length density. The model fit required considerations of tight association of water molecules around PEO chains and slight isotopic selectivity.

3D Printing of Aniline Tetramer-Grafted-Polyethylenimine and Pluronic F127 Composites for Electroactive Scaffolds.

PubMed

Dong, Shi-Lei; Han, Lu; Du, Cai-Xia; Wang, Xiao-Yu; Li, Lu-Hai; Wei, Yen

2017-02-01

Electroactive hydrogel scaffolds are fabricated by the 3D-printing technique using composites of 30% Pluronic F127 and aniline tetramer-grafted-polyethylenimine (AT-PEI) copolymers with various contents from 2.5% to 10%. The synthesized AT-PEI copolymers can self-assemble into nanoparticles with the diameter of ≈50 nm and display excellent electroactivity due to AT conjugation. The copolymers are then homogeneously distributed into 30% Pluronic F127 solution by virtue of the thermosensitivity of F127, denoted as F/AT-PEI composites. Macroscopic photographs of latticed scaffolds elucidate their excellent printability of F/AT-PEI hydrogels for the 3D-printing technique. The conductivities of the printed F/AT-PEI scaffolds are all higher than 2.0 × 10 -3 S cm -1 , which are significantly improved compared with that of F127 scaffold with only 0.94 × 10 -3 S cm -1 . Thus, the F/AT-PEI scaffolds can be considered as candidates for application in electrical stimulation of tissue regeneration such as repair of muscle and cardiac nerve tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and characterization of morin hydrate-loaded micellar nanocarriers for the effective management of Alzheimer's disease.

PubMed

Singh, Manpreet; Thakur, Vandana; Deshmukh, Rahul; Sharma, Amit; Rathore, M S; Kumar, Ajay; Mishra, Neeraj

2018-03-01

The aim of this study was to prepare and characterise oral delivery of morin hydrate-loaded micellar nanocarriers using Pluronic P127 and Pluronic F123 for the effective management of Alzheimer's disease. After administration of formulation brain and blood drug concentration were found to be highest for optimised morin hydrate-loaded micellar nanocarriers as compared to plain morin hydrate. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after administration of morin hydrate-loaded micellar nanocarriers as compared to disease control group. Chronic treatment with morin-loaded micelles significantly increased the memory in AlCl 3 induced Alzheimer's disease in Wistar rats.

Insights into the Formation and Properties of Templated Dual Mesoporous Titania with Enhanced Photocatalytic Activity.

PubMed

Naboulsi, Issam; Lebeau, Bénédicte; Michelin, Laure; Carteret, Cédric; Vidal, Loic; Bonne, Magali; Blin, Jean-Luc

2017-01-25

The one pot synthesis of dual mesoporous titania (2.3 and 7.7 nm) has been achieved from a mixture of fluorinated and Pluronic surfactants. The small and large mesopore networks are templated, respectively, by a fluorinated-rich liquid crystal and a Pluronic-rich liquid crystal, which are in equilibrium. After calcination at 350 °C, the amorphous walls are transformed into semicrystalline anatase preserving the mesoporous structure. Results concerning the photodegradation of methyl orange using the calcined photocatalysts highlight that the kinetic rate constant (k) determined for the dual mesoporous titania is 2.6 times higher than the k value obtained for the monomodal ones.

Pluronic F127/chitosan blend microspheres for mucoadhesive drug delivery

NASA Astrophysics Data System (ADS)

Gu, W. Z.; Hu, X. F.

2017-01-01

Pluronic F127/chitosan blend microspheres were prepared via emulsification and cross-linking process using glutaraldehyde as a cross-linker. Compared with chitosan microspheres fabricated under the same experimental conditions, blend microspheres exhibited better physical stability and higher swelling capacity. Puerarin, a traditional Chinese medicine, was incorporated into microparticlesas the model drug. The in vitro release of puerarin from blend microspheres was reduced because of the improved compatibility of the drug with the matrices. According to the results from in vitro adhesion experiments, mucoadhesive behavior of blend microspheres on a mucosa-like surface was similar to that of chitosan microspheres, despite their good ability of anti-protein absorption in solution.

Remotely Triggered Cisplatin Release from Carbon Nanocapsules by Radiofrequency Fields

PubMed Central

Raoof, Mustafa; Cisneros, Brandon T.; Guven, Adem; Corr, Stuart J.; Wilson, Lon J.; Curley, Steven A.

2013-01-01

The efficacy of nanoparticle-mediated drug delivery is limited by its peri-vascular sequestration, thus necessitating a strategy to trigger drug release from such intra-tumoral nanocarrier-drug depots. In our efforts to explore remotely-activated nanocarriers, we have developed carbon nanocapsules comprised of an ultrashort carbon nanotube shell (US-tubes) loaded with cisplatin (CDDP@US-tubes) and covered with a Pluronic surfactant wrapping to minimize passive release. We demonstrate here that non-invasive radiofrequency (RF) field activation of the CDDP@US-tubes produces heat that causes Pluronic disruption which triggers cisplatin release in an RF-dependent manner. Furthermore, release-dependent cytotoxicity is demonstrated in human hepatocellular carcinoma cell lines. PMID:23228421

Brushite foams--the effect of Tween® 80 and Pluronic® F-127 on foam porosity and mechanical properties.

PubMed

Unosson, Johanna; Montufar, Edgar B; Engqvist, Håkan; Ginebra, Maria-Pau; Persson, Cecilia

2016-01-01

Resorbable calcium phosphate based bone void fillers should work as temporary templates for new bone formation. The incorporation of macropores with sizes of 100 -300 µm has been shown to increase the resorption rate of the implant and speed up bone ingrowth. In this work, macroporous brushite cements were fabricated through foaming of the cement paste, using two different synthetic surfactants, Tween® 80 and Pluronic® F-127. The macropores formed in the Pluronic samples were both smaller and less homogeneously distributed compared with the pores formed in the Tween samples. The porosity and compressive strength (CS) were comparable to previously developed hydroxyapatite foams. The cement foam containing Tween, 0.5M citric acid in the liquid, 1 mass% of disodium dihydrogen pyrophosphate mixed in the powder and a liquid to powder ratio of 0.43 mL/g, showed the highest porosity values (76% total and 56% macroporosity), while the CS was >1 MPa, that is, the hardened cement could be handled without rupture of the foamed structure. The investigated brushite foams show potential for future clinical use, both as bone void fillers and as scaffolds for in vitro bone regeneration. © 2015 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

Alternative foaming agents for topical treatment of ulcerative colitis.

PubMed

Asama, Martin; Hall, Alex; Qi, Yijun; Moreau, Branden; Walthier, Heidi; Schaschwary, Matthew; Bristow, Blaine; Wang, Qun

2018-05-01

Approximately 907,000 Americans currently suffer from ulcerative colitis, a condition characterized by inflammation of the large intestine or rectum. Treatment of this disease often includes anti-inflammatory medication or immunosuppressants. Here foams are an attractive delivery platform, offering relatively high bioavailability, low systemic exposure, and improved patient comfort. However, the surfactants that generate these foams may adversely affect the diseased mucosa. Therefore, this project evaluated two alternative surfactants for use in topical drug delivery platforms: sodium caseinate and l-α-phosphatidylcholine. Both were compared to the biocompatible surfactant Pluronic ® F-127 using stability and density tests, and biocompatibility tests performed on mini-guts. Sodium caseinate foams were less stable but denser than Pluronic ® foams; however, they exhibited an unexpectedly low shelf-life. l-α-phosphatidylcholine was an unsuccessful primary foaming agent owing to poor foamability at low concentrations. Mini-gut growth rates were not significantly altered by surfactants, while morphology and an MTT assay identified Pluronic ® as the most biocompatible surfactant at higher concentrations. These results clarify the possible challenges that the tested surfactants may present in topical delivery platforms and show the relevance of permeability to tissue-surfactant interaction tests. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1448-1456, 2018. © 2017 Wiley Periodicals, Inc.

The multilayer nanoparticles for deep penetration of docetaxel into tumor parenchyma to overcome tumor microenvironment.

PubMed

Khaliq, Nisar Ul; Park, Dal Yong; Lee, Jae Young; Joo, Yeonhee; Oh, Keun Sang; Kim, Jung Seok; Kim, Jin-Seok; Kim, In-San; Kwon, Ick Chan; Yuk, Soon Hong

2016-10-01

Deep penetration of the anticancer drug, docetaxel (DTX), into tumor parenchyma was demonstrated to achieve improved chemotherapy. For this purpose, a multistage nanostructure was designed and characterized using the multilayer nanoparticles (NPs). The multilayer NPs had a core/shell structure. The core was composed of the DTX-loaded Pluronic NPs (diameter: 12nm) that were transferred into the inner side of vesicles to form the vesicle NPs. Förster resonance energy transfer (FRET) in the NPs was observed to verify the incorporation of the DTX-loaded Pluronic NPs into the inner side of the vesicles during the formation of the vesicle NPs. Subsequently, the vesicle NPs were stabilized through Pluronic-lipid bilayer interaction to form the multilayer NPs. To examine the morphology and size distribution of the multilayer NPs, transmittance electron microscopy and dynamic light scattering were used. In vitro release behavior and toxicity were observed to verify the functionality of the multilayer NPs as nanocarriers for cancer therapy. Multistage functionality was evaluated by cellular uptake and tissue distribution behaviors of the multilayer NPs. The biodistribution of the multilayer NPs and their antitumor efficacy were also observed to understand the role of multistage functionality for improved chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy.

PubMed

Oh, Keun Sang; Lee, Hwanbum; Kim, Jae Yeon; Koo, Eun Jin; Lee, Eun Hee; Park, Jae Hyung; Kim, Sang Yoon; Kim, Kwangmeyung; Kwon, Ick Chan; Yuk, Soon Hong

2013-01-10

The multilayer nanoparticles (NPs) were prepared for cancer-targeting therapy using the layer by layer approach. When drug-loaded Pluronic NPs were mixed with vesicles (liposomes) in the aqueous medium, Pluronic NPs were incorporated into the vesicles to form the vesicle NPs. Then, the multilayer NPs were formed by freeze-drying the vesicle NPs in a Pluronic aqueous solution. The morphology and size distribution of the multilayer NPs were observed using a TEM and a particle size analyzer. In order to apply the multilayer NPs as a delivery system for docetaxel (DTX), which is a model anticancer drug, the release pattern of the DTX was observed and the tumor growth was monitored by injecting the multilayer NPs into the tail veins of tumor (squamous cell carcinoma)-bearing mice. The cytotoxicity of free DTX (commercial DTX formulation (Taxotere®)) and the multilayer NPs was evaluated using MTT assay. We also evaluated the tumor targeting ability of the multilayer NPs using magnetic resonance imaging. The multilayer NPs showed excellent tumor targetability and antitumor efficacy in tumor-bearing mice, caused by the enhanced permeation and retention (EPR) effect. These results suggest that the multilayer NPs could be a potential drug delivery system for cancer-targeting therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

The components of shear stress affecting insect cells used with the baculovirus expression vector system.

PubMed

Weidner, Tobias; Druzinec, Damir; Mühlmann, Martina; Buchholz, Rainer; Czermak, Peter

2017-09-26

Insect-based expression platforms such as the baculovirus expression vector system (BEVS) are widely used for the laboratory- and industrial-scale production of recombinant proteins. Thereby, major drawbacks to gain high-quality proteins are the lytic infection cycle and the shear sensitivity of infected insect cells due to turbulence and aeration. Smaller bubbles were formerly assumed to be more harmful than larger ones, but we found that cell damage is also dependent on the concentration of protective agents such as Pluronic®. At the appropriate concentration, Pluronic forms a layer around air bubbles and hinders the attachment of cells, thus limiting the damage. In this context, we used microaeration to vary bubble sizes and confirmed that size is not the most important factor, but the total gas surface area in the reactor is. If the surface area exceeds a certain threshold, the concentration of Pluronic is no longer sufficient for cell protection. To investigate the significance of shear forces, a second study was carried out in which infected insect cells were cultivated in a hollow fiber module to protect them from shear forces. Both model studies revealed important aspects of the design and scale-up of BEVS processes for the production of recombinant proteins.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol

PubMed Central

Farace, Cristiano; Sánchez-Moreno, Paola; Orecchioni, Marco; Manetti, Roberto; Sgarrella, Francesco; Asara, Yolande; Peula-García, José M.; Marchal, Juan A.; Madeddu, Roberto; Delogu, Lucia G.

2016-01-01

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications. PMID:26728491

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

PubMed

Farace, Cristiano; Sánchez-Moreno, Paola; Orecchioni, Marco; Manetti, Roberto; Sgarrella, Francesco; Asara, Yolande; Peula-García, José M; Marchal, Juan A; Madeddu, Roberto; Delogu, Lucia G

2016-01-05

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study.

PubMed

Fares, Ahmed R; ElMeshad, Aliaa N; Kassem, Mohamed A A

2018-11-01

This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

Tuning Aerosol Particle Size Distribution of Metered Dose Inhalers Using Cosolvents and Surfactants

PubMed Central

Saleem, Imran Y.; Smyth, Hugh D. C.

2013-01-01

Objectives. The purpose of these studies was to understand the influence of cosolvent and surfactant contributions to particle size distributions emitted from solution metered dose inhalers (pMDIs) based on the propellant HFA 227. Methods. Two sets of formulations were prepared: (a) pMDIs-HFA 227 containing cosolvent (5–15% w/w ethanol) with constant surfactant (pluronic) concentration and (b) pMDIs-HFA 227 containing surfactant (0–5.45% w/w pluronic) with constant cosolvent concentration. Particle size distributions emitted from these pMDIs were analyzed using aerodynamic characterization (inertial impaction) and laser diffraction methods. Results. Both cosolvent and surfactant concentrations were positively correlated with median particle sizes; that is, drug particle size increased with increasing ethanol and pluronic concentrations. However, evaluation of particle size distributions showed that cosolvent caused reduction in the fine particle mode magnitude while the surfactant caused a shift in the mode position. These findings highlight the different mechanisms by which these components influence droplet formation and demonstrate the ability to utilize the different effects in formulations of pMDI-HFA 227 for independently modulating particle sizes in the respirable region. Conclusion. Potentially, the formulation design window generated using these excipients in combination could be used to match the particle size output of reformulated products to preexisting pMDI products. PMID:23984381

Pluronic F127 as auxiliary template for preparing nitrogen and oxygen dual doped mesoporous carbon cathode of lithium-oxygen batteries

NASA Astrophysics Data System (ADS)

Wu, Junwei; Liu, Yanchen; Cui, Yanhui; Ouyang, Jue; Baker, Andrew P.; Li, Zuohua; Zhang, Huayu

2018-02-01

Two mesoporous carbon foam (MCF) with nitrogen and oxygen dual doped are fabricated through facile templated hydrothermal process. One using fumed silica as single template is named S-MCF, and another using fumed silica and Pluronic F127 as double templates is named D-MCF. When using Pluronic F127 as an auxiliary template, the D-MCF shows different porous architecture and surface chemical nature from S-MCF, thus they behave differently as cathode materials in Li-O2 batteries. The D-MCF electrode exhibits a slight lower discharge capacity and an increased overpotential than that of S-SCF due to the decreased surface area and oxygen content. However, a better cycle stability was proved for the D-MCF electrode because of its higher nitrogen and lower oxygen content. When further composited with RuO2 nanoparticles, the RuO2/D-MCF cathode can operate 160 cycles with capacity cutoff of 500 mAh g-1, and this prolonged cycle life, compared to the 102 cycles of S-MCF cathode, verifies the superior electrochemical stability of D-MCF further and illuminates the crucial role of carbon substrate in the cathodes of Li-O2 batteries.

Biotin-targeted Pluronic(®) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells.

PubMed

Russo, Annapina; Pellosi, Diogo Silva; Pagliara, Valentina; Milone, Maria Rita; Pucci, Biagio; Caetano, Wilker; Hioka, Noboru; Budillon, Alfredo; Ungaro, Francesca; Russo, Giulia; Quaglia, Fabiana

2016-09-10

With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic(®) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic(®) F127 was conjugated with biotin, while Pluronic(®) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

Transport across the Blood-Brain Barrier of Pluronic Leptin

PubMed Central

Price, Tulin O.; Farr, Susan A.; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Kabanov, Alexander V.

2010-01-01

Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (Ki) = 0.272 ± 0.037 μl/g · min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0–30 min, p < 0.0005; 0–2 h, p < 0.001]. These studies show that the structure based Pluronic modification of leptin increased metabolic stability, reduced food intake, and allowed BBB penetration by a mechanism-independent BBB leptin transporter. PMID:20053933

Cross-Linked Micellar Spherical Nucleic Acids from Thermoresponsive Templates

PubMed Central

2017-01-01

A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles, followed by chemical cross-linking and subsequent removal of non-cross-linked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization, making them effective TLR-9 immunomodulatory agents. These constructs underscore the potential of SNAs in regulating immune response and address the relative lack of stability of noncovalent constructs. PMID:28207251

Preparation of curcumin-loaded pluronic F127/chitosan nanoparticles for cancer therapy

NASA Astrophysics Data System (ADS)

Phuc Le, Thi Minh; Phuc Pham, Van; Lua Dang, Thi Minh; Huyen La, Thi; Hanh Le, Thi; Huan Le, Quang

2013-06-01

Nanoparticles (NPs) have been proven to be an effective delivery system with few side effects for anticancer drugs. In this study, curcumin-loaded NPs have been prepared by an ionic gelation method using chitosan (Chi) and pluronic®F-127 (PF) as carriers to deliver curcumin to the target cancer cells. Prepared NPs were characterized using Zetasizer, fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our results showed that the encapsulation efficiency of curcumin was approximately 50%. The average size of curcumin-loaded PF/Chi NPs was 150.9 nm, while the zeta potential was 5.09 mV. Cellular uptake of curcumin-loaded NPs into HEK293 cells was confirmed by fluorescence microscopy.

Synthesis and structural characterization of ZnO-and CuO-NPs supported mesoporous silica materials (hexagonal SBA-15 and lamellar-SiO2)

NASA Astrophysics Data System (ADS)

El-Nahhal, Issa M.; Salem, Jamil K.; Tabasi, Nihal S.; Hempelmann, Rolf; Kodeh, Fawzi S.

2018-01-01

Two different mesoporous silica structures (hexagonal and lamellar) were synthesized via sol-gel method using a series of triblock copolymer (Pluronic) surfactants. L81, L61 & L31 surfactants form lamellar structure whereas P123 surfactant forms a hexagonal structure. CuO and ZnO nanoparticles (NPs) supported mesoporous silica were synthesized using impregnation method. The structural properties of these materials were investigated using several characterization techniques such as FTIR, XRD, SAXS, TEM and TGA. SAXS and TEM confirmed that the obtained mesoporous silica is based on the EO/PO ratio of Pluronic surfactants. They proved that the mesoporosity of silica is well maintained even after they loaded with metal oxide nanoparticles.

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate.

PubMed

Yang, Xiaoyan; Trinh, Hoang M; Agrahari, Vibhuti; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

2016-04-01

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09 ± 6.21%, 55.74 ± 6.26%, and 62.54 ± 3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Hydrophobic interaction mediated coating of Pluronics on mesoporous silica nanoparticle with stimuli responsiveness for cancer therapy.

PubMed

Sha, Luping; Wang, Da; Mao, Yuling; Shi, Wei; Gao, Tianbin; Zhao, Qinfu; Wang, Si-Ling

2018-05-22

In this research, a novel method was used to successfully make Pluronic P123 stably coated on mesoporous silica nanoparticles (MSN). That P123 and MSN co-constructed a drug delivery system (DDS) had not been reported. In this DDS, the coating of P123 was realized through hydrophobic interaction with octadecyl chain modified MSN. Experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segment could keep the nanoassemblies stable. For comparison, nanoassemblies consisted of P123 and octadecyl chain modified MSN with or without disulfide bond were prepared, which were denoted as PSMSN and PMSN respectively. Disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decrease toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with PMSN, PSMSN displayed redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in tumor was enhanced after coating on MSN by virtue of the "EPR" effect of nanoparticles compared with the solution form. . © 2018 IOP Publishing Ltd.

Optimization of long circulating mixed polymeric micelles containing vinpocetine using simple lattice mixture design, in vitro and in vivo characterization.

PubMed

El-Dahmy, Rania Moataz; Elsayed, Ibrahim; Elshafeey, Ahmed Hassen; Gawad, Nabaweya Abdelaziz Abd El; El-Gazayerly, Omaima Naim

2014-12-30

The aim of this study was to increase the in vivo mean residence time of vinpocetine after IV injection utilizing long circulating mixed micellar systems. Mixed micelles were prepared using Pluronics L121, P123 and F127. The systems were characterized by testing their entrapment efficiency, particle size, polydispersity index, zeta potential, transmission electron microscopy and in vitro drug release. Simple lattice mixture design was planned for the optimization using Design-Expert(®) software. The optimized formula was lyophilized, sterilized and imaged by scanning electron microscope. Moreover, the in vivo behavior of the optimized formula was evaluated after IV injection in rabbits. The optimized formula, containing 68% w/w Pluronic L121 and 32% w/w Pluronic F127, had the highest desirability value (0.621). Entrapment efficiency, particle size, polydispersity index and zeta potential of the optimized formula were 50.74 ± 3.26%, 161.50 ± 7.39 nm, 0.21 ± 0.03 and -22.42 ± 1.72 mV, respectively. Lyophilization and sterilization did not affect the characteristics of the optimized formula. Upon in vivo investigation in rabbits, the optimized formula showed a significantly higher elimination half-life and mean residence time than the market product. Finally, mixed micelles could be considered as a promising long circulating nanocarrier for lipophilic drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

The use of low molecular weight heparin-pluronic nanogels to impede liver fibrosis by inhibition the TGF-β/Smad signaling pathway.

PubMed

Lee, Ju-Hee; Lee, Hyunseung; Joung, Yoon Ki; Jung, Kyung Hee; Choi, Jong-Hoon; Lee, Don-Haeng; Park, Ki Dong; Hong, Soon-Sun

2011-02-01

Low molecular weight heparin (LH) has been reported to have anti-fibrotic and anti-cancer effects. To enhance the efficacy and minimize adverse effects of LH, a low molecular weight heparin-pluronic nanogel (LHP) was synthesized by conjugating carboxylated pluronic F127 to LH. The LHP reduced anti-coagulant activity by about 33% of the innate activity. Liver fibrosis was induced by the injection of 1% dimethylnitrosamine (DMN) in rats, and LH or LHP (1000 IU/kg body weight) was treated once daily for 4 weeks. LHP administration prevented DMN-mediated liver weight loss and decreased the values of aspartate transaminase, alanine transaminase, total bilirubin, and direct bilirubin. LHP markedly reduced the fibrotic area compared to LH. Also, LHP potently inhibited mRNA or protein expression of alpha-smooth muscle actin, collagen type I, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1 compared to LH, in DMN-induced liver fibrosis. In addition, LHP decreased the expression of transforming growth factor-β(1) (TGF-β(1)), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-β/Smad signaling pathway. The results support an LHP shows anti-fibrotic effect in the liver via inhibition of the TGF-β/Smad pathway as well as by the elimination of the extracellular matrix. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation for use in photodynamic therapy of lesions of the gastrointestinal tract.

PubMed

Bourre, Ludovic; Thibaut, Sonia; Briffaud, Amelie; Lajat, Youenn; Patrice, Thierry

2002-02-01

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX may play a role in the treatment of dysplastic Barrett's oesophagus. An ALA thermosetting gel Pluronic F-127) was developed and evaluated in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro studies of the influence of Pluronic F-127 percentage on thermosetting gel temperature, followed by the influence of ALA concentration on thermosetting temperature and ALA-gel stability as a function of time or temperature were studied. In vivo relationships between ALA doses and fluorescence were studied to determine the optimal concentration. Fluorescence measurement in vivo showed that ALA concentration and time had a nonlinear influence on protoporphyrin IX synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was reached, the maximum fluorescence being obtained after 4 h whatever the time of contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1) ALA-gel, and fluorescence intensities differed with time, reaching a maximum after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of Barrett's oesophagus, allowing easy application in liquid form at 4 degrees C and good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into treated mucosa. Copyright 2002 Elsevier Science Ltd.

Role of hydration and water coordination in micellization of Pluronic block copolymers.

PubMed

Šturcová, Adriana; Schmidt, Pavel; Dybal, Jiří

2010-12-15

Raman, attenuated total reflectance FTIR, near-infrared spectroscopy, and DFT calculations have been used in a study of aqueous solutions of three tri-block copolymers poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) or PEO-PPO-PEO with commercial names Pluronic PE6200, PE6400 and F68. It is shown that the process of micellization as a response to increased temperature is reflected in the hydroxyl stretching region of infrared and Raman spectra, which contains information both about restructuring of water and changes of polymer chains in polymer/water aggregates. Raman spectra exhibit differences between individual Pluronics even at temperatures below the critical micellization temperature (CMT). According to the attenuated total reflection (ATR) FTIR spectra, the same five water coordination types defined by the number of donated/accepted hydrogen bonds are present in interacting water as in bulk water. It indicates that models considering mixed states of water with different hydrogen bonding environments provide appropriate descriptions of bound water both below and above the CMT. Above the CMT, aggregate hydration increases in the order PE6400 < PE6200 < F68, although that does not fully correspond to the EO/PO ratio, and points to the differences in microstructure of aggregates formed by each copolymer. This study relates nanoscale phenomena (hydrophobic and hydrophilic hydration) with the mesoscale phenomenon of micellization. Copyright © 2010 Elsevier Inc. All rights reserved.

Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release

PubMed Central

Zhang, Lifen; Chen, Zhenzhen; Li, Yanfeng

2013-01-01

Polymeric gene-delivery vectors to achieve lack of toxicity and a balance between protection and DNA release remains a formidable challenge. Incorporating intracellular environment-responsive degradable bonds is an appreciable step toward developing safer transfection agents. In this study, novel, dual-degradable polycation copolymers (Pluronic-diacrylate [PA]–polyethyleneimine [PEI]–SS) were synthesized through the addition of low molecular weight (800 Da) PEI cross-linked with SS (PEI-SS) to PA. Three PA-PEI-SS copolymers (PA-PEI-SS1, 2, and 3) with different PEI-SS to Pluronic molar ratios were investigated and found to strongly condense plasmid DNA into positively charged nanoparticles with an average particle size of approximately 200 nm and to possess higher stability against DNase I digestion and sodium heparin. Disulfide and ester bonds of the copolymers were susceptible to intracellular redox conditions. In vitro experiments demonstrated that the PA-PEI-SS copolymers had significantly lower cytotoxicity and higher transfection efficiency in both BGC-823 and 293T cell lines than the controls of degradable PEI-SS and nondegradable 25 kDa PEI. Transfection activity was influenced by the PEI-SS content in the polymers and PA-PEI-SS1 showed the highest efficiency of the three copolymers. These studies suggest that these dual-degradable copolymers could be used as potential biocompatible gene delivery carriers. PMID:24109182

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation.

PubMed

El-Setouhy, Doaa Ahmed; Basalious, Emad B; Abdelmalak, Nevine Shawky

2015-08-01

Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due to their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic® p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap™ 80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro/in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap™ 80 exhibited the shortest in vitro/in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/Syloid® mixture and Sepitrap™ 80 could be promising for the development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of Self-assembly Mesoporous TiO2 Using Block Copolymer Pluronic PE6200 Template

NASA Astrophysics Data System (ADS)

Septina, W.; Yuliarto, B.; Nugraha

2008-03-01

In this research, nanocrystal mesoporous TiO2 powders were synthesized by sol-gel method, with TiCl4 as a precursor in methanol solution. Block copolymer Pluronic PE 6200 was used as pores template. It was found that from the XRD measurements, both at 400 °C and 450 °C calcination temperatures, resulted in nanocrystal TiO2 with anatase phase. Based on N2 adsorption characterization (BET method), TiO2 samples have surface area 108 m2/g and 88 m2/g for 400 °C and 450 °C calcination temperatures respectively. From Small-angle Neutron Scattering (SANS) patterns, it is investigated that TiO2 samples have mesoporous structure where the pore order degree depend on the calcination temperature.

Low-temperature roll-to-roll coating procedure of dye-sensitized solar cell photoelectrodes on flexible polymer-based substrates

NASA Astrophysics Data System (ADS)

Tinguely, Jean-Claude; Solarska, Renata; Braun, Artur; Graule, Thomas

2011-04-01

A new approach for the large-scale production of flexible photoelectrodes for dye-sensitized solar cells (DSSCs) is presented by roll-to-roll coating of a titanium dioxide nanodispersion containing the block copolymer 'Pluronic®' (PEOx-PPOy-PEOx, PEO: poly(ethylene oxide), PPO: poly(propylene oxide)). Functional DSSCs were assembled and the different coating procedures compared with respect to their solar power conversion efficiency. It is shown that the binder 'Pluronic' can be removed at processing temperatures as low as 140 °C, thus aiding achievement of sufficient adhesion to the ITO-PET support, higher porosity of the TiO2 layer and decreased crack appearance. Further optimization of this method is particularly promising when combined with other known low-temperature methods.

Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

PubMed

Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

2013-01-01

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries.

[In vitro evaluation of the gels properties prepared thermosensitive polymers as vehicles for administration substance by injection].

PubMed

Karolewicz, Bozena; Owczarek, Artur; Pluta, Janusz

2011-01-01

The aim of this study was to prepare a thermoresponsive formulations, which are a carrier for substance administered directly into site of action and which obtain sol-gel transitions at physiological ranges of temperature. The investigated formulations of liquid consistency at room temperature were obtained in sterile conditions on the basis of nonionic polymers Pluronic F-127, Pluronic F-68 and anionic polymer hyaluronic acid in different concentrations. The sol-gel transition temperature of the formulations was investigated and their physicochemical properties such as pH, density, osmotic pressure, sol-gel transition temperature, texture and release of vancomycin hydrochloride were studied. In vitro release experiments indicated that the optimised platform was able to prolong vancomycin hydrochloride release and their physico-chemical properties allow for application by injection form.

Drop spreading and gelation of thermoresponsive polymers.

PubMed

de Ruiter, R; Royon, L; Snoeijer, J H; Brunet, P

2018-04-25

Spreading and solidification of liquid droplets are elementary processes of relevance for additive manufacturing. Here we investigate the effect of heat transfer on spreading of a thermoresponsive solution (Pluronic F127) that undergoes a sol-gel transition above a critical temperature Tm. By controlling the concentration of Pluronic F127 we systematically vary Tm, while also imposing a broad range of temperatures of the solid and the liquid. We subsequently monitor the spreading dynamics over several orders of magnitude in time and determine when solidification stops the spreading. It is found that the main parameter is the difference between the substrate temperature and Tm, pointing to a local mechanism for arrest near the contact line. Unexpectedly, the spreading is also found to stop below the gelation temperature, which we attribute to a local enhancement in polymer concentration due to evaporation near the contact line.

Brushite foams—the effect of Tween® 80 and Pluronic® F‐127 on foam porosity and mechanical properties

PubMed Central

Montufar, Edgar B.; Engqvist, Håkan; Ginebra, Maria‐Pau; Persson, Cecilia

2016-01-01

Abstract Resorbable calcium phosphate based bone void fillers should work as temporary templates for new bone formation. The incorporation of macropores with sizes of 100 −300 µm has been shown to increase the resorption rate of the implant and speed up bone ingrowth. In this work, macroporous brushite cements were fabricated through foaming of the cement paste, using two different synthetic surfactants, Tween® 80 and Pluronic® F‐127. The macropores formed in the Pluronic samples were both smaller and less homogeneously distributed compared with the pores formed in the Tween samples. The porosity and compressive strength (CS) were comparable to previously developed hydroxyapatite foams. The cement foam containing Tween, 0.5M citric acid in the liquid, 1 mass% of disodium dihydrogen pyrophosphate mixed in the powder and a liquid to powder ratio of 0.43 mL/g, showed the highest porosity values (76% total and 56% macroporosity), while the CS was >1 MPa, that is, the hardened cement could be handled without rupture of the foamed structure. The investigated brushite foams show potential for future clinical use, both as bone void fillers and as scaffolds for in vitro bone regeneration. © 2015 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 67–77, 2016. PMID:25615405

Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis.

PubMed

Oh, Eun Jo; Oh, Se Heang; Lee, In Soo; Kwon, Oh Soo; Lee, Jin Ho

2016-05-01

Osteomyelitis is still considered to be one of the major challenges for orthopedic surgeons despite advanced antiseptic surgical procedures and pharmaceutical therapeutics. In this study, hydrophilized poly(methyl methacrylate) (PMMA) bone cements containing Pluronic F68 (EG79PG28EG79) as a hydrophilic additive and vancomycin (F68-VAcements) were prepared to allow the sustained release of the antibiotic for adequate periods of time without any significant loss of mechanical properties. The compressive strengths of the bone cements with Pluronic F68 compositions less than 7 wt% were not significantly different compared with the control vancomycin-loaded bone cement (VAcement). TheF68 (7 wt%)-VAcement showed sustained release of the antibiotic for up to 11 weeks and almost 100% release from the bone cement. It also prohibited the growth ofS. aureus(zone of inhibition) over six weeks (the required period to treat osteomyelitis), and it did not show any notable cytotoxicity. From an animal study using a femoral osteomyelitis rat model, it was observed that theF68 (7 wt%)-VAcement was effective for the treatment of osteomyelitis, probably as a result of the prolonged release of antibiotic from the PMMA bone cement. On the basis of these findings, it can be suggested that the use of Pluronic F68 as a hydrophilic additive for antibiotic-eluting PMMA bone cement can be a promising strategy for the treatment of osteomyelitis. © The Author(s) 2016.

Characterization of the paclitaxel loaded chitosan graft Pluronic F127 copolymer micelles conjugate with a DNA aptamer targeting HER-2 overexpressing breast cancer cells

NASA Astrophysics Data System (ADS)

Thach Nguyen, Kim; Nguyen, Thu Ha; Do, Dinh Ho; Huan Le, Quang

2017-03-01

In this work we report the isolation of DNA aptamer that is specifically bound to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. Paclitaxel (PTX) loaded chitosan graft Pluronic F127 copolymer micelles conjugate with a DNA aptamer was synthesized and its structure was confirmed by TEM image. This binary mixed system consisting of DNA aptamer modified Pluronic F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Morphology images confirmed the existence of PTX micelles, with an average size of approximately 86.22 ± 1.45 nm diameters. Drug release profile showed that the PTX conjugate maintained a sustained PTX release. From in vitro cell experiment it was shown that 89%-93%, 50%-58%, 55%-62%, 24%-28% and 2%-7% of the SK-BR-3, NS-VN-67, LH-VN-48, HT-VN-26 and NV-VN-31, respectively, were dead after 6-48 h. These results demonstrated a novel DNA aptamer-micelle assembly for efficient detection and a system for the delivery of PTX targeting specific HER-2 overexpressing. We have also successfully cultivated cancer tissues of explants from Vietnamese patients on a type I collagen substrate. The NS-VN-67, LH-VN-48, HT-VN-26 and NV-VN-31cell lines were used as cellular model sources for the study of chemotherapy drug in cancer.

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

PubMed Central

Chan, Hon Fai; Lin, Zhixiu; Wang, Yitao

2018-01-01

Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway. PMID:29491708

Pluronic®-bile salt mixed micelles.

PubMed

Patel, Vijay; Ray, Debes; Bahadur, Anita; Ma, Junhe; Aswal, V K; Bahadur, Pratap

2018-06-01

The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic ® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (D h ). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics ® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of polyethersulfone (PES)/silver nanoparticles (AgNPs)/polyethylene glycol (PEG) nanofiltration membrane

NASA Astrophysics Data System (ADS)

Johary, Fasihah; Jamaluddin, Nur Adibah; Rohani, Rosiah; Hassan, Abdul Rahman; Sharifuddin, Syazrin Syima; Isa, Mohd Hafez Mohd

2018-06-01

Nanofiltration is a membrane-based separation process that has been used widely in the separation and purification fields for various applications such as dye desalting, applications of water softening, pharmaceuticals and wastewater treatment. In this research, polyethersulfone (PES), polyethylene glycol (PEG), Pluronic F108 and silver nanoparticles (AgNPs) nanofiltration membrane was prepared using casting solution technique with N-methyl-2-pyrrolidone (NMP) was used as a solvent. The effects of Pluronic F108 and silver nanoparticles (AgNPs) concentrations in the casting solutions on the membrane performance/properties were also studied. The membrane pure water permeation (PWP) and salt rejection tests were carried out for membrane performance analysis. Scanning electron microscopy (SEM) was used for the membrane morphology characterization. Fourier transform infrared spectroscopy was utilized to identify functional groups in the membrane. Membrane with 2.0 wt.% of Pluronic F108 and 0.05 wt.% of AgNPs showed the best performances for both PWP (40.89 L/m2h) as well as permeation flux of salts solution of NaCl (43.95 L/m2h), Na2SO4 (21.16 L/m2h), MgCl2 (26.46 L/m2h) and MgSO4 (20.41 L/m2h). All fabricated membranes with different formulation of dope composition obtained high salts rejection in the range of 79% to 91%. SEM images showed addition of AgNPs has improved fabricated membrane morphology with higher pore density and larger macro-void structure.

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels.

PubMed

Alsaab, Hashem; Bonam, Sindhu Prabha; Bahl, Dherya; Chowdhury, Pallabita; Alexander, Kenneth; Boddu, Sai Hs

2016-01-01

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Development of chitosan/pluronic F108/polyethersulfone (PES) nanofiltration (NF) membrane for oily wastewater treatment

NASA Astrophysics Data System (ADS)

Hamzah, Norzakiah; Rohani, Rosiah; Hassan, Abdul Rahman; Sharifuddin, Syazrin Syima; Isa, Mohd Hafez Mohd

2018-06-01

This study discusses a new finding for nanofiltration membrane development using phase inversion technique whereby polyethersulfone (PES) polymer was added with surfactant and additive. This research focuses on the development of a membrane that is efficient in treating oily wastewater and reducing membrane's low permeation flux issues. Five PES nanofiltration membranes were synthesized with pluronic F108 surfactant and different amounts of chitosan additive for each formulation. Subsequently, the effect of adding surfactant and additive on membrane performance was studied. Results showed that the membrane with the optimal amount of chitosan gave the highest flux and the rejection of oily wastewater with up to 90%. In addition, Fourier transform-infrared (FTIR) spectroscopy technique was used to characterize and analyse the membrane's properties. Hence, the developed membranes were successfully characterized and proved to be a good treatment for oily wastewater.

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.

PubMed

Gu, Zhuojun; Wang, Meng; Fang, Qiongyan; Zheng, Huaiyu; Wu, Feiyue; Lin, Dai; Xu, Ying; Jin, Yi

2015-05-01

Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.

Relating emulsion stability to interfacial properties for pharmaceutical emulsions stabilized by Pluronic F68 surfactant.

PubMed

Powell, Kristin Conrad; Damitz, Robert; Chauhan, Anuj

2017-04-15

We explore mechanisms of emulsion stability for several systems using Pluronic F68 and a range of oils commonly used in pharmaceutics and cosmetics. We report measurements of dynamic emulsion drop size, zeta potential, and creaming time, as well as dynamic interfacial tension and interfacial viscoelasticity. Experiments show that with 1wt% Pluronic F68, soybean oil emulsions were the most stable with no creaming over six months, followed by isopropyl myristate, octanoic acid, and then ethyl butyrate. The eventual destabilization occurred due to the rising of large drops which formed through Ostwald ripening and coalescence. While Ostwald ripening is important, it is not the dominant destabilization mechanism for the time scale of interest in pharmaceutical emulsions. The more significant destabilization mechanism, coalescence, is reduced through surfactant adsorption, which decreases surface tension, increases surface elasticity, and adds a stearic hindrance to collisions. Though the measured values of elasticity obtained using a standard oscillatory pendant drop method did not correlate to emulsion stability, this is because the frequencies for the measurements were orders of magnitude below those relevant to coalescence in emulsions. However, we show that the high frequency elasticity obtained by fitting the surface tension data to a Langmuir isotherm has very good correlation with the emulsion stability, indicating that the elasticity of the interface plays a key role in stabilizing these pharmaceutical formulations. Further, this study highlights how these important high frequency elasticity values can be easily estimated from surface isotherms. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine.

PubMed

Ba, Wenqiang; Li, Zhou; Wang, Lisheng; Wang, Ding; Liao, Weiguo; Fan, Wentao; Wu, Yinai; Liao, Fengyun; Yu, Jianye

2016-08-01

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm(2)/h, significantly higher than that of gel (120.39 μg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm(2), significantly larger than that from gel (6.01 ± 0.04 μg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.

Developing Xenopus Embryos Recover by Compacting and Expelling Single-Wall Carbon Nanotubes

PubMed Central

Holt, Brian D.; Shawky, Joseph H.; Dahl, Kris Noel; Davidson, Lance A.; Islam, Mohammad F.

2015-01-01

Single-wall carbon nanotubes are high aspect ratio nanomaterials that are being developed for use in materials, technological and biological applications due to their high mechanical stiffness, optical properties, and chemical inertness. Because of their prevalence, it is inevitable that biological systems will be exposed to nanotubes, yet studies of the effects of nanotubes on developing embryos have been inconclusive and are lacking for single-wall carbon nanotubes exposed to the widely studied model organism Xenopus laevis (African clawed frog). Microinjection of experimental substances into the Xenopus embryo is a standard technique for toxicology studies and cellular lineage tracing. Here we report the surprising finding that superficial (12.5 ± 7.5 μm below the membrane) microinjection of nanotubes dispersed with Pluronic F127 into one-to-two cell Xenopus embryos resulted in the formation and expulsion of compacted, nanotube-filled, punctate masses, at the blastula to mid-gastrula developmental stages, which we call “boluses”. Such expulsion of microinjected materials by Xenopus embryos has not been reported before and is dramatically different from the typical distribution of the materials throughout the progeny of the microinjected cells. Previous studies of microinjections of nanomaterials such as nanodiamonds, quantum dots or spherical nanoparticles report that nanomaterials often induce toxicity and remain localized within the embryos. In contrast, our results demonstrate an active recovery pathway for embryos after exposure to Pluronic F127-coated nanotubes, which we speculate is due to a combined effect of the membrane activity of the dispersing agent, Pluronic F127, and the large aspect ratio of nanotubes. PMID:26153061

Developing Xenopus embryos recover by compacting and expelling single wall carbon nanotubes.

PubMed

Holt, Brian D; Shawky, Joseph H; Dahl, Kris Noel; Davidson, Lance A; Islam, Mohammad F

2016-04-01

Single wall carbon nanotubes are high aspect ratio nanomaterials being developed for use in materials, technological and biological applications due to their high mechanical stiffness, optical properties and chemical inertness. Because of their prevalence, it is inevitable that biological systems will be exposed to nanotubes, yet studies of the effects of nanotubes on developing embryos have been inconclusive and are lacking for single wall carbon nanotubes exposed to the widely studied model organism Xenopus laevis (African clawed frog). Microinjection of experimental substances into the Xenopus embryo is a standard technique for toxicology studies and cellular lineage tracing. Here we report the surprising finding that superficial (12.5 ± 7.5 µm below the membrane) microinjection of nanotubes dispersed with Pluronic F127 into one- to two-cell Xenopus embryos resulted in the formation and expulsion of compacted, nanotube-filled, punctate masses, at the blastula to mid-gastrula developmental stages, which we call "boluses." Such expulsion of microinjected materials by Xenopus embryos has not been reported before and is dramatically different from the typical distribution of the materials throughout the progeny of the microinjected cells. Previous studies of microinjections of nanomaterials such as nanodiamonds, quantum dots or spherical nanoparticles report that nanomaterials often induce toxicity and remain localized within the embryos. In contrast, our results demonstrate an active recovery pathway for embryos after exposure to Pluronic F127-coated nanotubes, which we speculate is due to a combined effect of the membrane activity of the dispersing agent, Pluronic F127, and the large aspect ratio of nanotubes. Copyright © 2015 John Wiley & Sons, Ltd.

Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers.

PubMed

Hou, Jian; Wang, Jing; Sun, E; Yang, Lei; Yan, Hong-Mei; Jia, Xiao-Bin; Zhang, Zhen-Hai

2016-11-01

An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol®HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol®HS15 and Pluronic F127, the particle size was 12.88 nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7 mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC 0-∞ ) compared with that of IS (AUC 0-∞ ) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.

Understanding the interaction of block copolymers with DMPC lipid bilayer using coarse-grained molecular dynamics simulations.

PubMed

Hezaveh, Samira; Samanta, Susruta; De Nicola, Antonio; Milano, Giuseppe; Roccatano, Danilo

2012-12-13

In this paper, we present a computational model of the adsorption and percolation mechanism of poloxamers (poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymers) across a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. A coarse-grained model was used to cope with the long time scale of the percolation process. The simulations have provided details of the interaction mechanism of Pluronics with lipid bilayer. In particular, the results have shown that polymer chains containing a PPO block with a length comparable to the DMPC bilayer thickness, such as P85, tends to percolate across the lipid bilayer. On the contrary, Pluronics with a shorter PPO chain, such as L64 and F38, insert partially into the membrane with the PPO block part while the PEO blocks remain in water on one side of the lipid bilayer. The percolation of the polymers into the lipid tail groups reduces the membrane thickness and increases the area per lipid. These effects are more evident for P85 than L64 or F38. Our findings are qualitatively in good agreement with published small-angle X-ray scattering experiments that have evidenced a thinning effect of Pluronics on the lipid bilayer as well as the role of the length of the PPO block on the permeation process of the polymer through the lipid bilayer. Our theoretical results complement the experimental data with a detailed structural and dynamic model of poloxamers at the interface and inside the lipid bilayer.

Unidirectional self-assembly of soft templated mesoporous carbons by zone annealing

NASA Astrophysics Data System (ADS)

Xue, Jiachen; Singh, Gurpreet; Qiang, Zhe; Karim, Alamgir; Vogt, Bryan D.

2013-08-01

Surfactant or block copolymer-templated mesoporous films have been extensively explored, but achieving mesostructure coherence and unidirectional orientation over macroscopic dimensions has remained quite challenging for these self-assembled systems. Here, we extend the concepts associated with zone refinement of crystalline materials to soft templated mesoporous carbon films based on the cooperative assembly of commercial non-ionic surfactants (block copolymers) and phenolic resin oligomers (resol) to provide macroscopic alignment of both cubic (FDU-16) and hexagonal (FDU-15) mesostructures. The average orientation of these mesophases is determined from rotation grazing incidence small angle X-ray scattering (GISAXS) measurements. For FDU-15 templated by Pluronic P123, the orientation factor for the zone-annealed film is 0.98 based on the average of the second Legendre polynomial, but this orientation deteriorates significantly during carbonization. Notably, a thermal stabilization step following zone annealing preserves the orientation of the mesostructure during carbonization. The orientation factor for an isotropic cubic structure (FDU-16 templated by Pluronic F127) is only 0.48 (based on the 111 reflection with incident angle 0.15°) for the same zone annealing protocol, but this illustrates the versatility of zone annealing to different mesostructures. Unexpectedly, zone annealing of FDU-15 templated by Pluronic F127 leads to stabilization of the mesostructure through carbonization, whereas this structure collapses fully during carbonization even after extended oven annealing; despite no clear macroscopic orientation of the cylindrical mesostructure from zone annealing. Thermal zone annealing provides a simple methodology to produce highly ordered and macroscopically oriented stable mesoporous carbon films, but the efficacy is strongly tied to the mobility of the template during the zone annealing.Surfactant or block copolymer-templated mesoporous films have been extensively explored, but achieving mesostructure coherence and unidirectional orientation over macroscopic dimensions has remained quite challenging for these self-assembled systems. Here, we extend the concepts associated with zone refinement of crystalline materials to soft templated mesoporous carbon films based on the cooperative assembly of commercial non-ionic surfactants (block copolymers) and phenolic resin oligomers (resol) to provide macroscopic alignment of both cubic (FDU-16) and hexagonal (FDU-15) mesostructures. The average orientation of these mesophases is determined from rotation grazing incidence small angle X-ray scattering (GISAXS) measurements. For FDU-15 templated by Pluronic P123, the orientation factor for the zone-annealed film is 0.98 based on the average of the second Legendre polynomial, but this orientation deteriorates significantly during carbonization. Notably, a thermal stabilization step following zone annealing preserves the orientation of the mesostructure during carbonization. The orientation factor for an isotropic cubic structure (FDU-16 templated by Pluronic F127) is only 0.48 (based on the 111 reflection with incident angle 0.15°) for the same zone annealing protocol, but this illustrates the versatility of zone annealing to different mesostructures. Unexpectedly, zone annealing of FDU-15 templated by Pluronic F127 leads to stabilization of the mesostructure through carbonization, whereas this structure collapses fully during carbonization even after extended oven annealing; despite no clear macroscopic orientation of the cylindrical mesostructure from zone annealing. Thermal zone annealing provides a simple methodology to produce highly ordered and macroscopically oriented stable mesoporous carbon films, but the efficacy is strongly tied to the mobility of the template during the zone annealing. Electronic supplementary information (ESI) available: GISAXS profiles for the FDU-15-F127 at φ = 0° and φ = 90° is included along with 2D GISAXS data for all azimuthal data associated with FDU-15-P123 to illustrate the azimuthal dependence on the diffraction patterns. See DOI: 10.1039/c3nr02821f

Biocompatible Au@Carbynoid/Pluronic-F127 nanocomposites synthesized by pulsed laser ablation assisted CO2 recycling

NASA Astrophysics Data System (ADS)

Del Rosso, T.; Louro, S. R. W.; Deepak, F. L.; Romani, E. C.; Zaman, Q.; Tahir; Pandoli, O.; Cremona, M.; Freire Junior, F. L.; De Beule, P. A. A.; De St. Pierre, T.; Aucelio, R. Q.; Mariotto, G.; Gemini-Piperni, S.; Ribeiro, A. R.; Landi, S. M.; Magalhães, A.

2018-05-01

Ligand-free carbynoid-encapsulated gold nanocomposites (Au@Carbynoid NCs) with blue-shifted localized surface plasmon resonance (LSPR) have been synthesized by CO2 recycling induced by pulsed laser ablation (PLA) of a solid gold target in aqueous solution with NaOH at pH 7.0. High Resolution Transmission Electron Microscopy (HRTEM) images at not destructive acceleration voltage of 80 kV revealed carbynoid nanocrystals around the gold core, associated to the intense bond length alternation (BLA) Raman mode of the carbon atomic wires (CAWs), centered at 2124 cm-1, observed in the Surface Enhanced Raman Scattering (SERS) spectra. It was verified that interlinking process with sp to sp2 conversion of the CAWs is induced both by high acceleration voltage in HRTEM and high irradiance of the excitation beam used in SERS measurements. Post synthesis mixing of Pluronic-F127 copolymer with pre-synthesized Au@Carbynoid NCs allows the formation of a fully biocompatible colloidal solution of Au@Carbynoid/Copolymer NCs. SERS investigation highlights that the Raman band of the BLA mode can be used as efficient Raman tag to monitor the functionalization of the NCs with the copolymer. The biocompatibility of the NCs was demonstrated performing a study of cytotoxicity using human skin fibroblasts. As proof of principle, it was demonstrated that the photodynamic activity of the bifunctional Au@Carbynoid/PF127 NCs in the presence of chlorin e6 (Ce6) drug can be enhanced inducing the aggregation state of the colloidal suspension. The stability of the colloidal dispersions of Au@Carbynoid NCs functionalized with Pluronic-F127 is verified after centrifugation in PBS (0.15 mol L-1 NaCl) solutions, confirming the possibility to use the green carbynoid based NCs as drug-carrier in biological applications.

Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

PubMed

Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

2017-05-30

The effect of surfactant chain lengths [sodium caprylate (C 8 ), Tween 20 (C 12 ), Tween 80 (C 18 )] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Heat capacity anomaly in a self-aggregating system: Triblock copolymer 17R4 in water

NASA Astrophysics Data System (ADS)

Dumancas, Lorenzo V.; Simpson, David E.; Jacobs, D. T.

2015-05-01

The reverse Pluronic, triblock copolymer 17R4 is formed from poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO): PPO14 - PEO24 - PPO14, where the number of monomers in each block is denoted by the subscripts. In water, 17R4 has a micellization line marking the transition from a unimer network to self-aggregated spherical micelles which is quite near a cloud point curve above which the system separates into copolymer-rich and copolymer-poor liquid phases. The phase separation has an Ising-like, lower consolute critical point with a well-determined critical temperature and composition. We have measured the heat capacity as a function of temperature using an adiabatic calorimeter for three compositions: (1) the critical composition where the anomaly at the critical point is analyzed, (2) a composition much less than the critical composition with a much smaller spike when the cloud point curve is crossed, and (3) a composition near where the micellization line intersects the cloud point curve that only shows micellization. For the critical composition, the heat capacity anomaly very near the critical point is observed for the first time in a Pluronic/water system and is described well as a second-order phase transition resulting from the copolymer-water interaction. For all compositions, the onset of micellization is clear, but the formation of micelles occurs over a broad range of temperatures and never becomes complete because micelles form differently in each phase above the cloud point curve. The integrated heat capacity gives an enthalpy that is smaller than the standard state enthalpy of micellization given by a van't Hoff plot, a typical result for Pluronic systems.

Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.

PubMed

Weinand, Christian; Pomerantseva, Irina; Neville, Craig M; Gupta, Rajiv; Weinberg, Eli; Madisch, Ijad; Shapiro, Frederic; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P

2006-04-01

Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.

EFFECT OF A PLURONIC® P123 FORMULATION ON THE NITRIC OXIDE-GENERATING DRUG JS-K

PubMed Central

Kaur, Imit; Kosak, Ken M.; Terrazas, Moises; Herron, James N.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

2014-01-01

Purpose O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare Pluronic® P123-formulated JS-K (P123/JS-K) with free JS-K. Methods We determined micelle size, shape, and critical micelle concentration of Pluronic® P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenog raft in NOD/SCID IL2Rγnull mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Results Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2Rγnull mice when compared to free JS-K-treated NOD/SCID IL2Rγnull mice. Conclusions Pluronic® P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K. PMID:25330743

Biomimetic Solid Lipid Nanoparticles of Sophorolipids Designed for Antileprosy Drugs.

PubMed

Kanwar, Rohini; Gradzielski, Michael; Mehta, S K

2018-06-22

The objective of the present work was to develop solid lipid nanoparticles (SLNs) as drug-encapsulating structures by the solvent injection method. In this report, for the first time the inherent potential of lactonic sophorolipid (glycolipid) was exploited to formulate SLNs. A range of different Pluronic copolymers were screened by dynamic and static light scattering with the aim of obtaining most stable SLNs. To comprehend the structure of the SLNs, techniques such as transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction were employed. A clear correlation between the type of Pluronic and size and stability of the SLNs could be drawn. The vector properties of the formed SLNs were assessed for both the encapsulated hydrophobic drugs-rifampicin and dapsone. To elucidate the transport mechanism of drug release, kinetic modeling was carried out on the drug release profiles. The promising results of sophorolipid-based SLNs have actually established a new arena beneath the significantly developed field of SLNs.

[In vitro evaluation of the gels properties prepared on Pluronic F-127 as vehicles for administration prolactin by injection].

PubMed

Karolewicz, Bozena; Pawlik-Gałczyńska, Anna; Pluta, Janusz; Ryszka, Florian

2011-01-01

The aim of this study was to prepare a thermoresponsive formulations, which are a carrier for proteins--prolactin administered directly into solid tumor and which obtain sol-gel transitions at physiological ranges of temperature. Prolactin (PRL) is a hormone that in vivo and in vitro exhibits antiangiogenic properties. Application of this protein in the proposed formulations can be particularly advantageous because of its relatively low stability and limited ability to transmembrane penetration. The paper prepared thermoresponsive carriers, based on nonionic polymer Pluronic F-127 with selected excipients such as dextran 7000, PEG 400, Tween 20 and Tween 80. The sol-gel transition temperature of the formulations was investigated and their physicochemical properties such as pH, density, osmotic pressure were studied. In the remainder of the work carried out tests of prolactin release from the proposed media. The results obtained indicate that a significant influence on the theological parameters obtained carriers and the availability of pharmaceutical composition of prolactin was developed formulation.

Multifunctional nanocarriers for biomedical applications

NASA Astrophysics Data System (ADS)

Bleul, R.; Thiermann, R.; Saatchi, K.; Häfeli, U. O.; Maskos, M.

2013-02-01

Polymeric vesicles (Pluronic® L-121) loaded with magnetic nanoparticles (MNP) and an anti-cancer drug (camptothecin) were prepared continuously in a micro mixing device. Characterization by TEM confirmed the successful incorporation of the MNP and DLS measurements showed a relatively narrow size distribution of the hybrid polymersomes. A very high drug loading of camptothecin (100 μg/ml in the polymersome formulation) was reached and a drug release study of loaded magnetic polymersomes has shown a sustained camptothecin release over several days. Carboxylation of Pluronic® L-121 was performed and enabled a further surface functionalization with bombesin, a 14 amino acid peptide, which binds specifically to the GRPR (gastrin releasing peptide receptor). This receptor is often overexpressed in tumor cells (e.g., human prostate cancer cells) and therefore a suitable target for cancer treatment. An additional fluorescence label with Alexa Fluor® 647 allow tracking of the polymersomes e.g., in cell experiments. Relaxivity measurements to evaluate the potential of magnetic polymersomes as MR contrast agent for in vivo imaging are in progress.

Activatable thermo-sensitive ICG encapsulated pluronic nanocapsules for temperature sensitive fluorescence tomography

NASA Astrophysics Data System (ADS)

Kwong, Tiffany C.; Nouizi, Farouk; Sampathkumaran, Uma; Zhu, Yue; Alam, Maksudul M.; Gulsen, Gultekin

2015-03-01

Fluorescent tomography has been hindered by poor tissue penetration and weak signal which results in poor spatial resolution and quantification accuracy. Recently, it has been reported that activatable temperature responsive fluorescent probes which respond to focused ultrasound heating can improve the resolution and quantification of fluorescent tomography in deep tissue. This has lead to a new imaging modality, "Temperature-modulated fluorescent tomography." This technique relies on activatable thermo-sensitive fluorescent nanocapsules for whose fluorescence quantum efficiency is temperature dependent. Within a 4-5° C temperature range, the fluorescent signal increase more than 10-fold. In this molecular probe, Indocyanine Green (ICG) is encapsulated inside the core of a thermo-reversible pluronic micelle. Here we show the fluorescence response and temperature range of the nanocapsules which have been optimized for a higher temperature range to be used for in vivo animal imaging. We report on the feasibility of these temperature-sensitive reversible nanocapsules for in vivo applications by studying the pharmacokinetics in a subcutaneous mouse tumor model in vivo.

In vivo triarylmethyl radical stabilization through encapsulation in Pluronic F-127 hydrogel

NASA Astrophysics Data System (ADS)

Abbas, Kahina; Boutier-Pischon, Audrey; Auger, Florian; Françon, Dominique; Almario, Antonio; Frapart, Yves-Michel

2016-09-01

In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are non-invasive technologies used to specifically detect and quantify paramagnetic species. However, the relative instability of spin probes such as triarylmethyl radicals limits their application to conduct oxygen quantification and mapping. In this study we encapsulated tetrathiatriarylmethyl radical (TAM; known as "Finland" probe) in Pluronic F-127 hydrogel (PF-127) in order to limit its degradation and evaluate its in vitro and in vivo EPR properties as a function of oxygen. Our results show that the EPR signal of encapsulated TAM in PF-127 hydrogel is similar to the one in solution. Although it is less sensitive to oxygen, it is suitable for oximetry. We also demonstrated that the incorporation of TAM in PF-127 hydrogel leads to an improved in vivo EPR stability of the radical under anesthesia. This new formulation enables high quality EPR imaging and oximetry and paves the way for the application of TAM radical-based probes in various biomedical fields.

Triblock copolymer-mediated synthesis of catalytically active gold nanostructures

NASA Astrophysics Data System (ADS)

Santos, Douglas C.; de Souza, Viviane C.; Vasconcelos, Diego A.; Andrade, George R. S.; Gimenez, Iara F.; Teixeira, Zaine

2018-04-01

The design of nanostructures based on poly(ethylene oxide)-poly(propylene)-poly(ethylene oxide) (PEO-PPO-PEO) and metal nanoparticles is becoming an important research topic due to their multiple functionalities in different fields, including nanomedicine and catalysis. In this work, water-soluble gold nanoparticles have been prepared through a green aqueous synthesis method using Pluronic F127 as both reducing and stabilizing agents. The size dependence (varying from 2 to 70 nm) and stability of gold nanoparticles were systematically studied by varying some parameters of synthesis, which were the polymer concentration, temperature, and exposure to UV-A light, being monitored by UV-Vis spectroscopy and TEM. Also, an elaborated study regarding to the kinetic of formation (nucleation and growth) was presented. Finally, the as-prepared Pluronic-capped gold nanoparticles have shown excellent catalytic activity towards the reduction of 4-nitrophenol to 4-aminophenol with sodium borohydride, in which a higher catalytic performance was exhibited when compared with gold nanoparticles prepared by classical reduction method using sodium citrate. [Figure not available: see fulltext.

Curcumin-Combretastatin Nanocells as Breast Cancer Cytotoxic and Antiangiogenic Agent

DTIC Science & Technology

2008-09-01

network of polyionic (e.g. polyethylenimine , polyacrylic acid, poly-L-lysine etc.) and neutral polymer chains (e.g. PEG, Pluronic/Poloxamer...devices were then mounted back to device stations placed inside a CO2 incubator. The CI was automatically monitored by the RT-CES system. The results

Toxicity analysis of various Pluronic F-68-coated carbon nanotubes on mesenchymal stem cells.

PubMed

Yao, Meng-Zhu; Hu, Yu-Lan; Sheng, Xiao-Xia; Lin, Jun; Ling, Daishun; Gao, Jian-Qing

2016-04-25

Carbon nanotubes (CNTs) have poor colloid stability in biological media and exert cytotoxic effects on mesenchymal stem cells (MSCs). Modification with polymeric surfactant is a widely used strategy to enhance water dispersibility of CNTs. This study investigated the toxic effects of various Pluronic F-68 (PF68)-coated multi-walled CNTs (MWCNTs) on rat bone marrow-derived MSCs.PF68-coated MWCNTs showed favorable biocompatibility to MSCs that the cell viability, apoptosis, and reactive oxygen species (ROS) were not altered after 24 h of co-incubation. Nevertheless, significant apoptosis induction and massive ROS release were found following extended exposure (48 and 72 h), and the toxic impact was dependent on the initial surface properties of the encapsulated MWCNTs. All the types of PF68-coated MWCNTs did not affect the cell-surface markers and in vivo biodistribution of MSCs. Our results suggest that proper polymer coating can reduce the acute toxicity of MWCNTs to MSCs but without altering their biological fate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anomalous Diffusion of Water in Lamellar Membranes Formed by Pluronic Polymers

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Ohl, Michael; Han, Youngkyu; Smith, Gregory; Do, Changwoo; Biology; Soft-Matter Division, Oak Ridge National Laboratory Team; Julich CenterNeutron Science Team

Water diffusion is playing an important role in polymer systems. We calculated the water diffusion coefficient at different layers along z-direction which is perpendicular to the lamellar membrane formed by Pluronic block copolymers (L62: (EO6-PO34-EO6)) with the molecular dynamics simulation trajectories. Water molecules at bulk layers are following the normal diffusion, while that at hydration layers formed by polyethylene oxide (PEO) and hydrophobic layers formed by polypropylene oxide (PPO) are following anomalous diffusion. We find that although the subdiffusive regimes at PEO layers and PPO layers are the same, which is the fractional Brownian motion, however, the dynamics are different, i.e. diffusion at the PEO layers is much faster than that at the PPO layers, and meanwhile it exhibits a normal diffusive approximation within a short time period which is governed by the localized free self-diffusion, but becomes subdiffusive after t >8 ps, which is governed by the viscoelastic medium. The Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy; and Zhe Zhang gratefully acknowledges financial support from Julich Center for Neutron Science.

Interaction of Curcumin with PEO-PPO-PEO block copolymers: a molecular dynamics study.

PubMed

Samanta, Susruta; Roccatano, Danilo

2013-03-21

Curcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood. In this paper, we propose a molecular dynamics simulation study of the interaction of Curcumin with block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted considering the smallest PEO and PPO oligomers and multiple chains of the block copolymer Pluronic P85. Our study shows that the more hydrophobic 1,2-dimethoxypropane (DMP) molecules and PPO block preferentially coat the Curcumin molecule. In the case of the Pluronic P85, simulation shows formation of a drug-polymer aggregate within 50 ns. This process leaves exposed the PEO part of the polymers, resulting in better solvation and stability of the drug in water.

Engineering muscle cell alignment through 3D bioprinting.

PubMed

Mozetic, Pamela; Giannitelli, Sara Maria; Gori, Manuele; Trombetta, Marcella; Rainer, Alberto

2017-09-01

Processing of hydrogels represents a main challenge for the prospective application of additive manufacturing (AM) to soft tissue engineering. Furthermore, direct manufacturing of tissue precursors with a cell density similar to native tissues has the potential to overcome the extensive in vitro culture required for conventional cell-seeded scaffolds seeking to fabricate constructs with tailored structural and functional properties. In this work, we present a simple AM methodology that exploits the thermoresponsive behavior of a block copolymer (Pluronic ® ) as a means to obtain good shape retention at physiological conditions and to induce cellular alignment. Pluronic/alginate blends have been investigated as a model system for the processing of C2C12 murine myoblast cell line. Interestingly, C2C12 cell model demonstrated cell alignment along the deposition direction, potentially representing a new avenue to tailor the resulting cell histoarchitecture during AM process. Furthermore, the fabricated constructs exhibited high cell viability, as well as a significantly improved expression of myogenic genes vs. conventional 2D cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2582-2588, 2017. © 2017 Wiley Periodicals, Inc.

A novel concept of overcoming the skin barrier using augmented liquid nanocrystals: Box-Behnken optimization, ex vivo and in vivo evaluation.

PubMed

Said, Mayada; Elsayed, Ibrahim; Aboelwafa, Ahmed A; Elshafeey, Ahmed H

2018-06-18

Agomelatine suffers from extensive inactivation through 1 st pass effect with a limited oral bioavailability (5%). The aim of this study was to formulate and optimize liquid nanocrystals (LNC) containing agomelatine to enhance the transdermal permeation of the drug. The independent factors of the employed Box-Behnken design were the Pluronic F127, deoxycholic acid sodium salt and propylene glycol percentages. On the other hand, particle size, polydispersity index, zeta potential, entrapment efficiency, cumulative amount permeated at certain time intervals and permeation enhancement ratio were considered as dependent responses. The optimized formulation was composed of 1.5% Pluronic F127 and 1.5% deoxycholic acid sodium salt and it was found to have significantly higher AUC 0-24h , AUC 0-∞ and elimination t 1/2 than that of the employed reference indicating the enhancement of the drug permeation. The obtained findings indicated the ability of the optimized LNC formulation to improve the drug bioavailability after its transdermal application. Copyright © 2018 Elsevier B.V. All rights reserved.

Thermo-triggerable self-assembly comprising cinnamoyl polymeric β cyclodextrin and cinnamoyl Pluronic F127.

PubMed

Wang, Min Hui; Jeong, Jae Hyun; Kim, Jin-Chul

2016-06-01

Thermo-triggerable self-assembly was prepared by co-dissolving cinnamoyl Pluronic F127 (CinPlu) and cinnamoyl polymeric β cyclodextrin (CinPβCD) in an aqueous phase. On TEM photo, the CinPlu/CinPβCD self-assembly was 100-200nm in diameter. The specific loading of Nile red (NR) in the assembly was calculated to be 5.5% (wt NR/wt polymer), and the molar ratio of NR to βCD residue in the assembly was about 0.89:1. No significant release of NR from the assembly was observed at 10°C and 20°C. However, when the temperature was raised to 30°C, 40°C, 50°C, and 60°C, the cumulative release amount in 5min was 17%, 25%, 32%, and 52%, respectively. The specific loading of doxorubicin (DOX) in the assembly was about 6.8% (wt DOX/wt polymer) (corresponding to the molar ratio of DOX to βCD residue was about 0.41:1). The DOX release from the assembly was proportional to the temperature of release medium. NR and DOX were likely to be expelled out of the cavity of βCD residue by the interaction of the thermally hydrophobicized Pluronic F127 chain (molecular piston) and the cavity of βCD residue (cylinder). After 4h-incubation with KB cell, DOX loaded in CinPlu/CinPβCD self-assembly was found to be internalized into the cancer cell more than free DOX, observed on a confocal laser scanning microscope and a fluorescence activated cell sorter. CinPlu/CinPβCD self-assembly enhanced the in vitro anti-cancer activity of DOX against KB cell without increasing significantly the in vitro toxicity of DOX against Raw264.7 cell. Copyright © 2016 Elsevier B.V. All rights reserved.

Study of the pluronic-silica interaction in synthesis of mesoporous silica under mild acidic conditions.

PubMed

Sundblom, Andreas; Palmqvist, Anders E C; Holmberg, Krister

2010-02-02

The interaction between silica and poly(ethylene oxide) (PEO) in water may appear trivial and it is generally stated that hydrogen bonding is responsible for the attraction. However, a literature search shows that there is not a consensus with respect to the mechanism behind the attractive interaction. Several papers claim that only hydrogen bonding is not sufficient to explain the binding. The silica-PEO interaction is interesting from an academic perspective and it is also exploited in the preparation of mesoporous silica, a material of considerable current interest. This study concerns the very early stage of synthesis of mesoporous silica under mild acidic conditions, pH 2-5, and the aim is to shed light on the interaction between silica and the PEO-containing structure directing agent. The synthesis comprises two steps. An organic silica source, tetraethylorthosilicate (TEOS), is first hydrolyzed and Pluronic P123, a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer, is subsequently added at different time periods following the hydrolysis of TEOS. It is shown that the interaction between the silica and the Pluronic is dependent both on the temperature and on the time between onset of TEOS hydrolysis and addition of the copolymer. The results show that the interaction is mainly driven by entropy. The effect of the synthesis temperature and of the time between hydrolysis and addition of the copolymer on the final material is also studied. The material with the highest degree of mesoorder was obtained when the reaction was performed at 20 degrees C and the copolymer was added 40 h after the start of TEOS hydrolysis. It is claimed that the reason for the good ordering of the silica is that whereas particle formation under these conditions is fast, the rate of silica condensation is relatively low.

Pd@Pt Core–Shell Nanoparticles with Branched Dandelion-like Morphology as Highly Efficient Catalysts for Olefin Reduction

EPA Science Inventory

A facile synthesis based on the addition of ascorbic acid to a mixture of Na2PdCl4, K2PtCl6, and Pluronic P123 results in highly branched core–shell nanoparticles (NPs) with a micro–mesoporous dandelion-like morphology comprising Pd core and Pt shell. The slow reduction kinetics ...

Evaluation of a novel vaginal bromocriptine mesylate formulation: a pilot study.

PubMed

Darwish, Atef M; Hafez, Ehsan; El-Gebali, Ibraheem; Hassan, Saher B

2005-04-01

Because of the frequent side effects found with oral bromocriptine, we created two formulas of vaginal bromocriptine suppositories to compare with vaginal application of bromocriptine tablets. The formula containing bromocriptine and a releasing agent (Pluronic F127) showed an increased dissolution rate, 39-fold greater than that of the pure drug alone, and subsequently was effective in lowering serum prolactin.

Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic((R))P85, an in vitro cell line and in vivo biodistribution studies on rat model.

PubMed

Shah, Neha; Chaudhari, Kiran; Dantuluri, Prudhviraju; Murthy, R S R; Das, Susobhan

2009-08-01

The development of multidrug resistance (due to drug efflux by P-glycoproteins) is a major drawback with the use of paclitaxel (PTX) in the treatment of cancer. The rationale behind this study is to prepare PTX nanoparticles (NPs) for the reversal of multidrug resistance based on the fact that PTX loaded into NPs is not recognized by P-glycoproteins and hence is not effluxed out of the cell. Also, the intracellular penetration of the NPs could be enhanced by anchoring transferrin (Tf) on the PTX-PLGA-NPs. PTX-loaded PLGA NPs (PTX-PLGA-NPs), Pluronic((R))P85-coated PLGA NPs (P85-PTX-PLGA-NPs), and Tf-anchored PLGA NPs (Tf-PTX-PLGA-NPs) were prepared and evaluted for cytotoxicity and intracellular uptake using C6 rat glioma cell line. A significant increase in cytotoxicity was observed in the order of Tf-PTX-PLGA-NPs > P85-PTX-PLGA-NPs > PTX-PLGA-NPs in comparison to drug solution. In vivo biodistribution on male Sprague-Dawley rats bearing C6 glioma (subcutaneous) showed higher tumor PTX concentrations in animals administered with PTX-NPs compared to drug solution.

Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4-loaded hydrogel directs hard tissue bioengineering.

PubMed

Diniz, Ivana M A; Carreira, Ana C O; Sipert, Carla R; Uehara, Cindi M; Moreira, Maria S N; Freire, Laila; Pelissari, Cibele; Kossugue, Patrícia M; de Araújo, Daniele R; Sogayar, Mari C; Marques, Márcia M

2018-06-01

Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic ® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic ® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering. © 2017 Wiley Periodicals, Inc.

Graphene oxide sheets-based platform for induced pluripotent stem cells culture: toxicity, adherence, growth and application

NASA Astrophysics Data System (ADS)

Durán, Marcela; Andrade, Patricia F.; Durán, Nelson; Luzo, Angela C. M.; Fávaro, Wagner J.

2015-05-01

It was prepared the graphene oxide (GO) sheets by suspension of GO in ultrapure deionized water or in Pluronic F-68 using a ultrasonicator bath. Total characterization of GO sheets was carried out. The results on suspension of GO in water showed excellent growth and cell adhesion. GO/Pluronic F-68 platform for the growth and adhesion of adipose-derived stem cells (ASCs) that exhibits excellent properties for these processes. GO in water suspension exhibited an inhibition of the cell growth over 5 μg/mL In vivo study with GO suspended in water (100 μg/mL) on Fisher 344 rats via i.p. administration showed low toxicity. Despite GO particle accumulates in the intraperitoneal cavity, this fact did not interfere with the final absorption of GO. The AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels (liver function) did not differ statistically in all experimental groups. Also, creatinine and urea levels (renal function) did not differ statistically in all experimental groups. Taking together, the data suggest the great potential of graphene oxide sheets as platform to ACSs, as well as, new material for treatment several urological diseases.

Static and dynamic investigations of poly(aspartic acid) and Pluronic F127 complex prepared by self-assembling in aqueous solution

NASA Astrophysics Data System (ADS)

Nita, Loredana E.; Chiriac, Aurica P.; Bercea, Maria; Nistor, Manuela T.

2015-12-01

The present investigation is focused on evaluation of self-assembling ability in aqueous solutions of two water soluble polymers: poly(aspartic acid) (PAS) and Pluronic F127 (PL). The intermolecular complexes, realized between polyacid and neutral copolymer surfactant in different ratios, have been studied by combining various characterization techniques as rheology, DLS, spectroscopy, microscopy, chemical imaging, and zeta potential determination, measurements performed in static and/or dynamic conditions. In static conditions, when the equilibrium state between PAS/PL polymeric pair was reached, and depending on the polymers mixture composition, and of experimental rheological conditions, positive or negative deviations from the additive rule are registered. Conformational changes of the macromolecular chains and correspondingly physical interactions are generated between PL and PAS for self-assembly and the formation of interpolymer complex as suprastructure with micellar configuration. The phenomenon was better evidenced in case of 1/1 wt ratio between the two polymers. In dynamic conditions of determination, during ;in situ; evaluation of the hydrodynamic diameter, zeta potential and conductivity, when the equilibrium state is not reached and as result either the intermolecular bonds are not achieved, the self-assembling process is not so obvious evidenced.

Structure, rheology and shear alignment of Pluronic block copolymer mixtures.

PubMed

Newby, Gemma E; Hamley, Ian W; King, Stephen M; Martin, Christopher M; Terrill, Nicholas J

2009-01-01

The structure and flow behaviour of binary mixtures of Pluronic block copolymers P85 and P123 is investigated by small-angle scattering, rheometry and mobility tests. Micelle dimensions are probed by dynamic light scattering. The micelle hydrodynamic radius for the 50/50 mixture is larger than that for either P85 or P123 alone, due to the formation of mixed micelles with a higher association number. The phase diagram for 50/50 mixtures contains regions of cubic and hexagonal phases similar to those for the parent homopolymers, however the region of stability of the cubic phase is enhanced at low temperature and concentrations above 40 wt%. This is ascribed to favourable packing of the mixed micelles containing core blocks with two different chain lengths, but similar corona chain lengths. The shear flow alignment of face-centred cubic and hexagonal phases is probed by in situ small-angle X-ray or neutron scattering with simultaneous rheology. The hexagonal phase can be aligned using steady shear in a Couette geometry, however the high modulus cubic phase cannot be aligned well in this way. This requires the application of oscillatory shear or compression.

Inhibition of Connexin 43 Hemichannel-Mediated ATP Release Attenuates Early Inflammation During the Foreign Body Response

PubMed Central

Calder, Bennett W.; Rhett, Joshua Matthew; Bainbridge, Heather; Fann, Stephen A.; Gourdie, Robert G.

2015-01-01

Background: In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. Methods: In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. Results: JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. Conclusions: These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital aspect of this work is that it demonstrates that targeted molecular therapeutics, such as JM2, provide the capacity to regulate inflammation in a clinically relevant system. PMID:25760687

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer

PubMed Central

Gong, Chang Yang; Shi, Shuai; Dong, Peng Wei; Zheng, Xiu Ling; Fu, Shao Zhi; Guo, Gang; Yang, Jing Liang; Wei, Yu Quan; Qian, Zhi Yong

2009-01-01

Background Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy. Results A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate. Conclusion The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields. PMID:19210779

Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early inflammation during the foreign body response.

PubMed

Calder, Bennett W; Matthew Rhett, Joshua; Bainbridge, Heather; Fann, Stephen A; Gourdie, Robert G; Yost, Michael J

2015-06-01

In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital aspect of this work is that it demonstrates that targeted molecular therapeutics, such as JM2, provide the capacity to regulate inflammation in a clinically relevant system.

Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting

NASA Astrophysics Data System (ADS)

Zhang, Ruo-Yun; Wang, Zhao-Yang; Yang, Xiao-Quan; Xuan, Yang; Cheng, Kai; Li, Cheng; Song, Xian-Lin; An, Jie; Hou, Xiao-Lin; Zhao, Yuan-Di

2018-02-01

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

The effect of the nonionic block copolymer pluronic P85 on gene expression in mouse muscle and antigen-presenting cells.

PubMed

Gaymalov, Zagit Z; Yang, Zhihui; Pisarev, Vladimir M; Alakhov, Valery Yu; Kabanov, Alexander V

2009-02-01

DNA vaccines can be greatly improved by polymer agents that simultaneously increase transgene expression and activate immunity. We describe here Pluronic P85 (P85), a triblock copolymer of ethylene oxide (EO) and propylene oxide (PO) EO(26)-PO(40)-EO(26). Using a mouse model we demonstrate that co-administration of a bacterial plasmid DNA with P85 in a skeletal muscle greatly increases gene expression in the injection site and distant organs, especially the draining lymph nodes and spleen. The reporter expression colocalizes with the specific markers of myocytes and keratinocytes in the muscle, as well as dendritic cells (DCs) and macrophages in the muscle, lymph nodes and spleen. Furthermore, DNA/P85 and P85 alone increase the systemic expansion of CD11c+ (DC), and local expansion of CD11c+, CD14+ (macrophages) and CD49b+ (natural killer) cell populations. DNA/P85 (but not P85) also increases maturation of local DC (CD11c+ CD86+, CD11c+ CD80 +, and CD11c+ CD40+. We suggest that DNA/P85 promotes the activation and recruitment of the antigen-presenting cells, which further incorporate, express and carry the transgene to the immune system organs.

Patterning N-type and S-type neuroblastoma cells with Pluronic F108 and ECM proteins.

PubMed

Corey, Joseph M; Gertz, Caitlyn C; Sutton, Thomas J; Chen, Qiaoran; Mycek, Katherine B; Wang, Bor-Shuen; Martin, Abbey A; Johnson, Sara L; Feldman, Eva L

2010-05-01

Influencing cell shape using micropatterned substrates affects cell behaviors, such as proliferation and apoptosis. Cell shape may also affect these behaviors in human neuroblastoma (NBL) cancer, but to date, no substrate design has effectively patterned multiple clinically important human NBL lines. In this study, we investigated whether Pluronic F108 was an effective antiadhesive coating for human NBL cells and whether it would localize three NBL lines to adhesive regions of tissue culture plastic or collagen I on substrate patterns. The adhesion and patterning of an S-type line, SH-EP, and two N-type lines, SH-SY5Y and IMR-32, were tested. In adhesion assays, F108 deterred NBL adhesion equally as well as two antiadhesive organofunctional silanes and far better than bovine serum albumin. Patterned stripes of F108 restricted all three human NBL lines to adhesive stripes of tissue culture plastic. We then investigated four schemes of applying collagen and F108 to different regions of a substrate. Contact with collagen obliterates the ability of F108 to deter NBL adhesion, limiting how both materials can be applied to substrates to produce high fidelity NBL patterning. This patterned substrate design should facilitate investigations of the role of cell shape in NBL cell behavior. Copyright 2009 Wiley Periodicals, Inc.

Patterning N-type and S-type Neuroblastoma Cells with Pluronic F108 and ECM Proteins

PubMed Central

Corey, Joseph M.; Gertz, Caitlyn C.; Sutton, Thomas J.; Chen, Qiaoran; Mycek, Katherine B.; Wang, Bor-Shuen; Martin, Abbey A.; Johnson, Sara L.; Feldman, Eva L.

2009-01-01

Influencing cell shape using micropatterned substrates affects cell behaviors, such as proliferation and apoptosis. Cell shape may also affect these behaviors in human neuroblastoma (NBL) cancer, but to date, no substrate design has effectively patterned multiple clinically important human NBL lines. In this study, we investigated whether Pluronic F108 was an effective anti-adhesive coating for human NBL cells and whether it would localize three NBL lines to adhesive regions of tissue culture plastic or collagen I on substrate patterns. The adhesion and patterning of an S-type line, SH-EP, and two N-type lines, SH-SY5Y and IMR-32, were tested. In adhesion assays, F108 deterred NBL adhesion equally as well as two anti-adhesive organofunctional silanes and far better than bovine serum albumin. Patterned stripes of F108 restricted all three human NBL lines to adhesive stripes of tissue culture plastic. We then investigated four schemes of applying collagen and F108 to different regions of a substrate. Contact with collagen obliterates the ability of F108 to deter NBL adhesion, limiting how both materials can be applied to substrates to produce high fidelity NBL patterning. This patterned substrate design should facilitate investigations of the role of cell shape in NBL cell behavior. PMID:19609877

Self-assembled block copolymer-nanoparticle hybrids: interplay between enthalpy and entropy.

PubMed

Sarkar, Biswajit; Alexandridis, Paschalis

2012-11-13

The dispersion of nanoparticles in ordered block copolymer nanostructures can provide control over particle location and orientation, and pave the way for engineered nanomaterials that have enhanced mechanical, electrical, or optical properties. Fundamental questions pertaining to the role of enthalpic and entropic particle-polymer interactions remain open and motivate the present work. We consider here a system of 10.6 nm silica nanoparticles (NPs) dispersed in ordered cylinders formed by hydrated poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic P105: EO(37)PO(56)EO(37)). Protonation of silica was used to vary the NP-polymer enthalpic interactions, while polar organic solvents (glycerol, DMSO, ethanol, and DMF) were used to modulate the NP-polymer entropic interactions. The introduction of deprotonated NPs in the place of an equal mass of water did not affect the lattice parameter of the PEO-PPO-PEO block copolymer hexagonal lyotropic liquid crystalline structures. However, the dispersion of protonated NPs led to an increase in the lattice parameter, which was attributed to stronger NP-polymer hydrogen bonding (enthalpic) interactions. Dispersion of protonated NPs into cylindrical structures formed by Pluronic P105 in 80/20 water/organic solvents does not influence the lattice parameter, different from the case of protonated NP in plain water. Organic solvents appear to screen the NP-polymer hydrogen bonding interactions.

Release of a Wound-healing Agent from PLGA Microspheres in a Thermosensitive Gel

DTIC Science & Technology

2013-01-01

have been associated with infectious complications due to the nature of wounding, giving rise to significant devitalized tissue, con- tamination of...Command, Military Infectious Dis- eases, and Combat Casualty Care Research Directorates. References [1] C. K. Murray, “ Infectious disease complications...pluronic-based metronidazole in situ gelling formulations for vaginal application,” Acta Pharmaceutica, vol. 62, no. 1, pp. 59–70, 2012. [24] K. D. Thakker

Effect of Ternary Solutes on the Evolution of Structure and Gel Formation in Amphiphilic Copolymer Solutions

NASA Astrophysics Data System (ADS)

Meznarich, Norman Anthony Kang

Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronic surfactants) undergo reversible and temperature-dependent micellization and arrangement into cubic ordered lattices known as "micelle gels". The macroscopic behavior of the ordering is a transition from a liquid to a gel. While the phase behavior and gel structure of pure Pluronic surfactant solutions have been well studied, less is known about the effects of added ternary solutes. In this dissertation, a comprehensive investigation into the effects of the added pharmaceutical methylparaben on solutions of F127 ranging from 10 to 30 wt% was conducted in order to better understand the behavior of F127 in multicomponent pharmaceutical formulations. The viscoelastic properties of F127 gel formation were studied using rheometry, where heating rates of 0.1, 1, and 10 degrees C/min were also used to probe the kinetics of the gel transition. In solutions containing methylparaben, F127 gelation occurred at up to 15 degrees C lower temperatures and was accelerated by a factor of three to four. Small angle x-ray scattering (SAXS) was used to characterize the structure of the ordered domains, and how they were affected by the presence of dissolved pharmaceuticals. It was found that ordered domain formation changed from heterogeneous nucleation and growth to possible homogeneous nucleation and growth. A roughly 2% reduction in the cubic lattice parameter was also observed for solutions containing methylparaben. Differential scanning calorimetry (DSC) experiments were performed on a series of different Pluronic surfactants in order to characterize the micellization behavior as a function of PPO center block length and PEO/PPO ratio. Added methylparaben suppressed the micellization endotherm, the degree of suppression depending linearly on the amount of added methylparaben, as well as the length of the PPO center block and PEO/PPO ratio. This dissertation yielded a thorough characterization of the changes in micellization and gelation behavior in F127 gels as a result of added pharmaceuticals. Previously unobserved behavior such as the onset of ordered domain formation in F127 gels was observed, and a greater understanding of the interactions between amphiphilic copolymer solutions and dissolved solutes was achieved.

Pullulan-coated phospholipid and Pluronic F68 complex nanoparticles for carrying IR780 and paclitaxel to treat hepatocellular carcinoma by combining photothermal therapy/photodynamic therapy and chemotherapy

PubMed Central

Zhang, Tao; Wan, Guoyun; Chen, Bowei; Xiong, Qingqing; Zhang, Jie; Zhang, Wenxue; Wang, Yinsong

2017-01-01

IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy. PMID:29255359

3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction

PubMed Central

Liu, An; Xue, Guang-huai; Sun, Miao; Shao, Hui-feng; Ma, Chi-yuan; Gao, Qing; Gou, Zhong-ru; Yan, Shi-gui; Liu, Yan-ming; He, Yong

2016-01-01

Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone-ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical. PMID:26875826

On the binding of calcium by micelles composed of carboxy-modified pluronics measured by means of differential potentiometric titration and modeled with a self-consistent-field theory.

PubMed

Lauw, Y; Leermakers, F A M; Cohen Stuart, M A; Pinheiro, J P; Custers, J P A; van den Broeke, L J P; Keurentjes, J T F

2006-12-19

We perform differential potentiometric titration measurements for the binding of Ca2+ ions to micelles composed of the carboxylic acid end-standing Pluronic P85 block copolymer (i.e., CAE-85 (COOH-(EO)26-(PO)39-(EO)26-COOH)). Two different ion-selective electrodes (ISEs) are used to detect the free calcium concentration; the first ISE is an indicator electrode, and the second is a reference electrode. The titration is done by adding the block copolymers to a known solution of Ca2+ at neutral pH and high enough temperature (above the critical micellization temperature CMT) and various amount of added monovalent salt. By measuring the difference in the electromotive force between the two ISEs, the amount of Ca2+ that is bound by the micelles is calculated. This is then used to determine the binding constant of Ca2+ with the micelles, which is a missing parameter needed to perform molecular realistic self-consistent-field (SCF) calculations. It turns out that the micelles from block copolymer CAE-85 bind Ca2+ ions both electrostatically and specifically. The specific binding between Ca2+ and carboxylic groups in the corona of the micelles is modeled through the reaction equilibrium -COOCa+ <==> -COO- + Ca2+ with pKCa = 1.7 +/- 0.06.

Effects of different combinations of nanocrystallization technologies on avanafil nanoparticles: in vitro, in vivo and stability evaluation.

PubMed

Soliman, Kareem AbuBakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

2017-01-30

The study investigated the effects of different combined top-down and bottom-up nanocrystallization technologies on particle size and solid state of avanafil nanoparticles. Combined antisolvent precipitation-ultrasonication (sonoprecipitation) technique was adopted to prepare 18 formulas according to 3 2 .2 1 factorial design using 3 stabilizers; Tween 80, polyvinyl alcohol (PVA) and Pluronic F68 at different concentrations with different cryoprotectants. Particle size analysis of the lyophilized formulas showed that Tween 80 was an effective nanoparticles stabilizer in contrast to Pluronic F68 and PVA which failed to prevent nanoparticles flocculation when they were used at high concentration. The combined effects of nanonization and amorphism contributed to the improvement in solubility. Further processing of the sonoprecipitated formulas by high pressure homogenization (HPH) (modified NANOEDGE™ technology) resulted in further size reduction of PVA-stabilized particles, while it stimulated flocculation of Tween-stabilized nanoparticles. Nevertheless, all of the homogenized formulas partially retrieved their crystallinity which reduced their solubility. Non-homogenized formula 2E composed of 1:2 (avanafil: Tween) with glucose as cryoprotectant, exhibited 13.68- and 2.59-fold improvement in solubility and in vitro dissolution, respectively. This formula had oral bioavailability of 137.02% relative to Spedra ® tablets and it maintained its nanosize, amorphism and dissolution behavior over 6 months of storage under stress conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis, Characterization, and Evaluation of Pluronic-Based β-Cyclodextrin Polyrotaxanes for Mobilization of Accumulated Cholesterol from Niemann-Pick Type C Fibroblasts

PubMed Central

Collins, Christopher J.; McCauliff, Leslie A.; Hyun, Seok-Hee; Zhang, Zhaorui; Paul, Lake N.; Kulkarni, Aditya; Zick, Klaus; Wirth, Mary; Storch, Judith; Thompson, David H.

2015-01-01

Several lines of evidence suggest that β-cyclodextrin (β-CD) derivatives initiate the efflux of accumulated, unesterified cholesterol from the late endosomal/lysosomal compartment in Niemann Pick C (NPC) disease models. Unfortunately, repeated injections or continuous infusions of current β-CD therapies are required to sustain suppression of symptoms and prolong life. In an effort to make CD treatment a more viable option by boosting efficacy and improving pharmacokinetics, a library of Pluronic surfactant-based β-CD polyrotaxanes has been developed using biocompatible poly(ethylene glycol) (PEG)–polypropylene glycol (PPG)–PEG triblock copolymers. These compounds carry multiple copies of β-CD as shown by 1H NMR, 2D nuclear Overhouser effect spectroscopy, gel permeation chromatography/multiangle light scattering, analytical ultracentrifugation analysis, matrix assisted laser desorption/ionization mass spectrometry, and diffusion-ordered spectroscopy. Analyses of free β-cyclodextrin contamination in the compounds were made by reverse phase high pressure liquid chromatography and hydrophilic interaction liquid chromatography. Dethreading kinetics were studied by reverse phase high pressure liquid chromatography, UV/vis, and 1H NMR analysis. Filipin staining studies using npc2−/− fibroblasts show significant reversal of cholesterol accumulation after treatment with polyrotaxane compounds. The rate and efficacy of reversal is similar to that achieved by equivalent amounts of monomeric β-CD alone. PMID:23560535

Synthesis, characterization, and evaluation of pluronic-based β-cyclodextrin polyrotaxanes for mobilization of accumulated cholesterol from Niemann-Pick type C fibroblasts.

PubMed

Collins, Christopher J; McCauliff, Leslie A; Hyun, Seok-Hee; Zhang, Zhaorui; Paul, Lake N; Kulkarni, Aditya; Zick, Klaus; Wirth, Mary; Storch, Judith; Thompson, David H

2013-05-14

Several lines of evidence suggest that β-cyclodextrin (β-CD) derivatives initiate the efflux of accumulated, unesterified cholesterol from the late endosomal/lysosomal compartment in Niemann Pick C (NPC) disease models. Unfortunately, repeated injections or continuous infusions of current β-CD therapies are required to sustain suppression of symptoms and prolong life. In an effort to make CD treatment a more viable option by boosting efficacy and improving pharmacokinetics, a library of Pluronic surfactant-based β-CD polyrotaxanes has been developed using biocompatible poly(ethylene glycol) (PEG)-polypropylene glycol (PPG)-PEG triblock copolymers. These compounds carry multiple copies of β-CD as shown by (1)H NMR, 2D nuclear Overhouser effect spectroscopy, gel permeation chromatography/multiangle light scattering, analytical ultracentrifugation analysis, matrix assisted laser desorption/ionization mass spectrometry, and diffusion-ordered spectroscopy. Analyses of free β-cyclodextrin contamination in the compounds were made by reverse phase high pressure liquid chromatography and hydrophilic interaction liquid chromatography. Dethreading kinetics were studied by reverse phase high pressure liquid chromatography, UV/vis, and (1)H NMR analysis. Filipin staining studies using npc2(-/-) fibroblasts show significant reversal of cholesterol accumulation after treatment with polyrotaxane compounds. The rate and efficacy of reversal is similar to that achieved by equivalent amounts of monomeric β-CD alone.

Ratiometric Nanothermometer Based on Rhodamine Dye-Incorporated F127-Melamine-Formaldehyde Polymer Nanoparticle: Preparation, Characterization, Wide-Range Temperature Sensing, and Precise Intracellular Thermometry.

PubMed

Wu, Youshen; Liu, Jiajun; Ma, Jingwen; Liu, Yongchun; Wang, Ya; Wu, Daocheng

2016-06-15

A series of fluorescent nanothermometers (FTs) was prepared with Rhodamine dye-incorporated Pluronic F-127-melamine-formaldehyde composite polymer nanoparticles (R-F127-MF NPs). The highly soluble Rhodamine dye molecules were bound with Pluronic F127 micelles and subsequently incorporated in the cross-linked MF resin NPs during high-temperature cross-link treatment. The morphology and chemical structure of R-F127-MF NPs were characterized with dynamic light scattering, electron microscopy, and Fourier-transform infrared (FTIR) spectra. Fluorescence properties and thermoresponsivities were analyzed using fluorescence spectra. R-F127-MF NPs are found to be monodispersed, presenting a size range of 88-105 nm, and have bright fluorescence and high stability in severe treatments such as autoclave sterilization and lyophilization. By simultaneously incorporating Rhodamine B and Rhodamine 110 (as reference) dyes at a doping ratio of 1:400 in the NPs, ratiometric FTs with a high sensibility of 7.6%·°C(-1) and a wide temperature sensing range from -20 to 110 °C were obtained. The FTs exhibit good stability in solutions with varied pH, ionic strengths, and viscosities and have similar working curves in both intracellular and extracellular environments. Cellular temperature variations in Hela cells during microwave exposure were successfully monitored using the FTs, indicating their considerable potential applications in the biomedical field.

Two-Dimensional Holey Nanoarchitectures Created by Confined Self-Assembly of Nanoparticles via Block Copolymers: From Synthesis to Energy Storage Property

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Lele; Fang, Zhiwei; Li, Jing

Advances in liquid-phase exfoliation and surfactant-directed anisotropic growth of two-dimensional (2D) nanosheets have enabled their rapid development. However, it remains challenging to develop assembly strategies that lead to the construction of 2D nanomaterials with well-defined geometry and functional nanoarchitectures that are tailored to specific applications. Here we report a facile self-assembly method leading to the controlled synthesis of 2D transition metal oxide (TMO) nanosheets containing a high density of holes. We utilize graphene oxide sheets as a sacrificial template and Pluronic copolymers as surfactant. By using ZnFe 2O 4 (ZFO) nanoparticles as a model material, we demonstrate that by tuningmore » the molecular weight of the Pluronic copolymers that we can incorporate the ZFO particles and tune the size of the holes in the sheets. The resulting 2D ZFO nanosheets offer synergistic characteristics including increased electrochemically active surface areas, shortened ion diffusion paths, and strong inherent mechanical properties, leading to enhanced lithium-ion storage properties. Post-cycling characterization confirms that the samples maintain structural integrity after electrochemical cycling. In conclusion, our findings demonstrate that this template-assisted self-assembly method is a useful bottom-up route for controlled synthesis of 2D nanoarchitectures, and these holey 2D nanoarchitectures are promising for improving the electrochemical performance of nextgeneration lithium-ion batteries.« less

Ultrasonic Processing Technique as a Green Preparation Approach for Diacerein-Loaded Niosomes.

PubMed

Khan, Muhammad Imran; Madni, Asadullah; Hirvonen, Jouni; Peltonen, Leena

2017-07-01

In this study, the feasibility of ultrasonic processing (UP) technique as green preparation method for production of poorly soluble model drug substance, diacerein, loaded niosomes was demonstrated. Also, the effects of different surfactant systems on niosomes' characteristics were analyzed. Niosomes were prepared using both the green UP technique and traditional thin-film hydration (TFH) technique, which requires the use of environmentally hazardous organic solvents. The studied surfactant systems were Span 20, Pluronic L64, and their mixture (Span 20 and Pluronic L64). Both the production techniques produced well-defined spherical vesicles, but the UP technique produced smaller and more monodisperse niosomes than TFH. The entrapment efficiencies with the UP method were lower than with TFH, but still at a feasible level. All the niosomal formulations released diacerein faster than pure drug, and the drug release rates from the niosomes produced by the UP method were higher than those from the TFH-produced niosomes. With UP technique, the optimum process conditions for small niosomal products with low PDI values and high entrapment efficiencies were obtained when 70% amplitude and 45-min sonication time were used. The overall results demonstrated the potency of UP technique as an alternative fast, cost-effective, and green preparation approach for production of niosomes, which can be utilized as drug carrier systems for poorly soluble drug materials.

Efficacy of a Multiplex Paclitaxel Emission Stent Using a Pluronic® Mixture Membrane versus a Covered Metal Stent in Malignant Biliary Obstruction: A Prospective Randomized Comparative Study.

PubMed

Jang, Sung Ill; Lee, Se Joon; Jeong, Seok; Lee, Don Haeng; Kim, Myung-Hwan; Yoon, Hong Jin; Lee, Dong Ki

2017-07-15

A drug-eluting stent for unresectable malignant biliary obstruction was developed to increase stent patency by preventing tumor ingrowth. The safety and efficacy of a new generation of metallic stents covered with a paclitaxel-incorporated membrane using a Pluronic ® mixture (MSCPM-II) were compared prospectively with those of covered metal stents (CMSs) in patients with malignant biliary obstructions. This study was initially designed as a prospective randomized trial but was closed early because of a high incidence of early occlusion. Therefore, the data were analyzed using the intent-to-treat method. A total of 72 patients with unresectable distal malignant biliary obstructions were prospectively enrolled. The two groups did not differ significantly in basic characteristics and mean follow-up period (MSCPM-II 194 days vs CMS 277 days, p=0.063). Stent occlusion occurred in 14 patients (35%) who received MSCPM-II and in seven patients (21.9%) who received CMSs. Stent patency and survival time did not significantly differ between the two groups (p=0.355 and p=0.570). The complications were mild and resolved by conservative management in both groups. There were no significant differences in stent patency or patient survival in MSCPM-II and CMS patients with malignant biliary obstructions.

Development of chitosan graft pluronic®F127 copolymer nanoparticles containing DNA aptamer for paclitaxel delivery to treat breast cancer cells

NASA Astrophysics Data System (ADS)

Thach Nguyen, Kim; Le, Duc Vinh; Do, Dinh Ho; Huan Le, Quang

2016-06-01

HER-2/ErbB2/Neu(HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves a therapeutic target for breast cancer. In this study, we aimed to isolate DNA aptamer (Ap) that specifically bind to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. We developed a novel multifunctional composite micelle with surface modification of Ap for targeted delivery of paclitaxel. This binary mixed system consisting of Ap modified pluronic®F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Polymeric micelles had a spherical shape and were self-assemblies of block copolymers of approximately 86.22 ± 1.45 nm diameter. PTX could be loaded with high encapsulation efficiency (83.28 ± 0.13%) and loading capacity (9.12 ± 0.34%). The release profile were 29%-35% in the first 12 h and 85%-93% after 12 d at pH 7.5 of receiving media. The IC50 doses by MTT assay showed the greater activity of nanoparticles loaded paclitaxel over free paclitaxel and killed cells up to 95% after 6 h. These results demonstrated unique assembly with the capacity to function as an efficient detection and delivery vehicle in the biological living system.

Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells

PubMed Central

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Xu, Ronald X.; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2016-01-01

Dual responsive nanoparticles are developed for co-delivery of multiple anticancer drugs to target the drug resistance mechanisms of cancer stem-like cells (CSCs). The nanoparticles consist of four polymers approved by the Food and Drug Administration (FDA) for medical use: Poly(D,L-lactide-co-glycolide) (PLGA), Pluronic F127 (PF127), chitosan, and hyaluronic acid (HA). By combining PLGA and PF127 together, more stable and uniform-sized nanoparticles can be obtained than using PLGA or PF127 alone. The HA is used for not only actively targeting CSCs to reduce their drug resistance due to dormancy (i.e., slow metabolism), but also replacing the commonly used poly(vinyl alcohol) as a stabilizing agent to synthesize the nanoparticles using the double-emulsion approach and to allow for acidic pH-triggered drug release and thermal responsiveness. Besides minimizing drug efflux from CSCs, the nanoparticles encapsulated with doxorubicin hydrochloride (DOX, hydrophilic) and irinotecan (CPT, hydrophobic) to inhibit the activity of topoisomerases II and I, respectively, can fight against the CSC drug resistance associated with their enhanced DNA repair and anti-apoptosis. Ultimately, the two drugs-laden nanoparticles can be used to efficiently destroy the CSCs both in vitro and in vivo with up to ~500 times of enhancement compared to the simple mixture of the two drugs. PMID:26344365

Development of eco-friendly submicron emulsions stabilized by a bio-derived gum.

PubMed

Pérez-Mosqueda, Luis María; Ramírez, Pablo; Trujillo-Cayado, Luis Alfonso; Santos, Jenifer; Muñoz, José

2014-11-01

Many traditional organic solvents are being gradually replaced by ecofriendly alternatives. D-Limonene is a terpenic (bio)-solvent that fulfils the requirements to be considered a green solvent. D-Limonene sub-micron emulsions suffer from Ostwald ripening destabilization. In this study, we examined the influence of the addition of a natural gum (rosin gum) to D-limonene in order to prevent Ostwald ripening. This contribution deals with the study of emulsions formulated with a mixture of D-limonene and rosin gum as dispersed phase and Pluronic PE9400 as emulsifier. The procedure followed for the development of these formulations was based on the application of product design principles. This led to the optimum ratio rosin gum/D-limonene and subsequently to the optimum surfactant concentration. The combination of different techniques (rheology, laser diffraction and multiple light scattering) was demonstrated to be a powerful tool to assist in the prediction of the emulsions destabilization process. Not only did the addition of rosin gum highly increase the stability of these emulsions by inhibiting the Ostwald ripening, but it also reduced the emulsions droplet size. Thus, we found that stable sub-micron D-limonene-in-water emulsions have been obtained in the range 3-6 wt% Pluronic PE-9400 by means of a single-step rotor/stator homogenizing process. Copyright © 2014 Elsevier B.V. All rights reserved.

Two-Dimensional Holey Nanoarchitectures Created by Confined Self-Assembly of Nanoparticles via Block Copolymers: From Synthesis to Energy Storage Property

DOE PAGES

Peng, Lele; Fang, Zhiwei; Li, Jing; ...

2017-12-20

Advances in liquid-phase exfoliation and surfactant-directed anisotropic growth of two-dimensional (2D) nanosheets have enabled their rapid development. However, it remains challenging to develop assembly strategies that lead to the construction of 2D nanomaterials with well-defined geometry and functional nanoarchitectures that are tailored to specific applications. Here we report a facile self-assembly method leading to the controlled synthesis of 2D transition metal oxide (TMO) nanosheets containing a high density of holes. We utilize graphene oxide sheets as a sacrificial template and Pluronic copolymers as surfactant. By using ZnFe 2O 4 (ZFO) nanoparticles as a model material, we demonstrate that by tuningmore » the molecular weight of the Pluronic copolymers that we can incorporate the ZFO particles and tune the size of the holes in the sheets. The resulting 2D ZFO nanosheets offer synergistic characteristics including increased electrochemically active surface areas, shortened ion diffusion paths, and strong inherent mechanical properties, leading to enhanced lithium-ion storage properties. Post-cycling characterization confirms that the samples maintain structural integrity after electrochemical cycling. In conclusion, our findings demonstrate that this template-assisted self-assembly method is a useful bottom-up route for controlled synthesis of 2D nanoarchitectures, and these holey 2D nanoarchitectures are promising for improving the electrochemical performance of nextgeneration lithium-ion batteries.« less

Pullulan-coated phospholipid and Pluronic F68 complex nanoparticles for carrying IR780 and paclitaxel to treat hepatocellular carcinoma by combining photothermal therapy/photodynamic therapy and chemotherapy.

PubMed

Wang, Dan; Zhang, Sipei; Zhang, Tao; Wan, Guoyun; Chen, Bowei; Xiong, Qingqing; Zhang, Jie; Zhang, Wenxue; Wang, Yinsong

2017-01-01

IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy.

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

PubMed Central

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was −10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs. PMID:28260893

Effect of phospholipid-based formulations of Boswellia serrata extract on the solubility, permeability, and absorption of the individual boswellic acid constituents present.

PubMed

Hüsch, Jan; Gerbeth, Kathleen; Fricker, Gert; Setzer, Constanze; Zirkel, Jürgen; Rebmann, Herbert; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

2012-10-26

Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-β-boswellic acid (1) and acetyl-11-keto-β-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration.

Effects of surface chemistry on the optical properties and cellular interaction of lanthanide-based nanoparticles

NASA Astrophysics Data System (ADS)

Pedraza, Francisco J.; Avalos, Julio C.; Mimun, Lawrence C.; Yust, Brian G.; Tsin, Andrew; Sardar, Dhiraj K.

2015-03-01

Fluorescent nanoparticles (NPs) such as KYb2F7:Tm3+ potential in biomedical applications due to their ability to absorb and emit within the biological window, where near infrared light is less attenuated by soft tissue. This results in less tissue damage and deeper tissue penetration making it a viable candidate in biological imaging. Another big factor in determining their ability to perform in a biological setting is the surface chemistry. Biocompatible coatings, including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), pluronic and folic acid are commonly used because they pose several advantages such as ease of functionalization, better dispersion, and higher cellular uptake. To study the effects of the NP surface chemistry, KYb2F7:Tm3+ a solvothermal method using PEG, PVP, pluronic acid, and folic acid as a capping agent, followed by thorough optical characterizations. Optical changes were thoroughly studied and compared using absorption, emission, and quantum yield data. Cell viability was obtained by treating Rhesus Monkey Retinal Endothelial cells (RhREC) with KYb2F7:Tm3+ and counting viable cells following a 24 hour uptake period. The work presented will compare the optical properties and toxicity dependency on the surface chemistry on KYb2F7:Tm3+. The results will also indicate that KYb2F7:Tm3+ nanoparticles are viable candidates for various biomedical applications.

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630.

PubMed

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was -10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs.

Topical nanoparticulate formulation of drugs for ocular keratitis

NASA Astrophysics Data System (ADS)

Yang, Xiaoyan

The primary objective of this project is to develop drug-loaded polymeric nanoparticles suspended in a biocompatible gel for topical delivery of therapeutic agents commonly employed in the treatment of ocular viral/bacterial keratitis. PART 1: Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV), D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1) induced viral corneal keratitis. NP containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Cytotoxicity studies suggested that all NP formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases. Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NP are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV. LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells. PART 2: PLGA NP of hydrocortisone butyrate (HB) suspended in thermosensitive PLGA-PEG-PLGA gel were developed for the treatment of bacterial corneal keratitis. Experimental designs were employed in order to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. NP containing HB were prepared by an oil-in-water (O/W) emulsion evaporation technique with different surfactants including polyvinyl alcohol (PVA), pluronic F-108 and chitosan. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels and zero-order release kinetics was observed. Percentage of uptake in HCEC after 4 h was 59.09+/-6.21% for PVA-emulsified NP relative to 55.74+/-6.26% for pluronic-emulsified NP, and 62.54+/-3.30% for chitosan-emulsified NP, respectively. In HCEC cell line, chitosan-emulsified NP with chitosan showed highest cellular uptake efficiency over PVA- and pluronic-emulsified NP. However, NP with chitosan indicated significant cytotoxicity under 200 and 500 ?g/mL after 48 h, while NP with PVA and pluronic showed no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Injectible bodily prosthetics employing methacrylic copolymer gels

DOEpatents

Mallapragada, Surya K.; Anderson, Brian C.

2007-02-27

The present invention provides novel block copolymers as structural supplements for injectible bodily prosthetics employed in medical or cosmetic procedures. The invention also includes the use of such block copolymers as nucleus pulposus replacement materials for the treatment of degenerative disc disorders and spinal injuries. The copolymers are constructed by polymerization of a tertiary amine methacrylate with either a (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer, such as the commercially available Pluronic.RTM. polymers, or a poly(ethylene glycol) methyl ether polymer.

Surfactant-Templated Mesoporous Metal Oxide Nanowires

DOE PAGES

Luo, Hongmei; Lin, Qianglu; Baber, Stacy; ...

2010-01-01

We demore » monstrate two approaches to prepare mesoporous metal oxide nanowires by surfactant assembly and nanoconfinement via sol-gel or electrochemical deposition. For example, mesoporous Ta 2 O 5 and zeolite nanowires are prepared by block copolymer Pluronic 123-templated sol-gel method, and mesoporous ZnO nanowires are prepared by electrodeposition in presence of anionic surfactant sodium dodecyl sulfate (SDS) surfactant, in porous membranes. The morphologies of porous nanowires are studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses.« less

Facile synthesis and application of a carbon foam with large mesopores.

PubMed

Fu, Liling; Qi, Genggeng; Sahore, Ritu; Sougrat, Rachid; DiSalvo, Francis J; Giannelis, Emmanuel P

2013-11-28

By combining elements of hard- and soft-templating, a facile synthesis method for carbon foams with large mesopores has been demonstrated. A commercial Pluronic surfactant was used as the structure-directing agent as well as the carbon precursor. No micelle swelling agent or post treatment is necessary to enlarge mesopores. As such this method requires fewer synthesis steps and is highly scalable. The as-synthesized meso-carbons showed potential applications in the fields of carbon oxide capture and lithium-sulfur batteries.

pH-sensitive methacrylic copolymer gels and the production thereof

DOEpatents

Mallapragada, Surya K [Ames, IA; Anderson, Brian C [Lake Bluff, IA

2007-05-15

The present invention provides novel gel forming methacrylic blocking copolymers that exhibit cationic pH-sensitive behavior as well as good water solubility. The copolymers are constructed by polymerization of a tertiary amine methacrylate with either a (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer, such as the commercially available Pluronic.RTM. polymers, or a poly(ethylene glycol)methyl ether polymer. The polymers may be used for drug and gene delivery, protein separation, as structural supplements, and more.

Soft-templating synthesis of mesoporous graphitic carbon nitride with enhanced photocatalytic H2 evolution under visible light.

PubMed

Yan, Hongjian

2012-04-07

g-C(3)N(4) with worm-like pore and narrow pore size distribution was synthesized by using Pluronic P123 as soft-template. The worm-like porous g-C(3)N(4) not only possesses high BET surface area but also redshifts its absorbance edge up to 800 nm, and shows photocatalytic activity even when the irradiation light λ > 700 nm. This journal is © The Royal Society of Chemistry 2012

Accelerated stability assay (ASA) for colloidal systems.

PubMed

Chong, Josephine Y T; Mulet, Xavier; Boyd, Ben J; Drummond, Calum J

2014-05-12

Assessment of the stability of colloidal systems, in particular lyotropic liquid crystalline dispersions, such as cubosomes and hexosomes, is typically performed qualitatively or with limited throughput on specialized instruments. Here, an accelerated stability assay for colloidal particles has been developed in 384-well plates with standard laboratory equipment. These protocols enable quantitative assessments of colloidal stability. To demonstrate the applicability of the assay, several steric stabilizers for cubic phase nanostructured particles (cubosomes) have been compared to the current "gold standard" Pluronic F127.

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127

PubMed Central

Gonzales, Marcela; Mitsumori, Lee M.; Kushleika, John V.; Rosenfeld, Michael E.; Krishnan, Kannan M.

2010-01-01

Magnetic nanoparticles are promising molecular imaging agents due to their relative high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline, and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model was quantified using concurrent assaying; a LDH assay to determine cytotoxicity and an MTS assay to determine viability for a 24 hour incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents need to be carefully constructed to avoid interference and erroneous results. PMID:20623517

Poly(ester amine) Composed of Polyethylenimine and Pluronic Enhance Delivery of Antisense Oligonucleotides In Vitro and in Dystrophic mdx Mice

PubMed Central

Wang, Mingxing; Wu, Bo; Tucker, Jason D; Bollinger, Lauren E; Lu, Peijuan; Lu, Qilong

2016-01-01

A series of poly(esteramine)s (PEAs) constructed from low molecular weight polyethyleneimine (LPEI) and Pluronic were evaluated for the delivery of antisense oligonuclotides (AOs), 2′-O-methyl phosphorothioate RNA (2′-OMePS) and phosphorodiamidate morpholino oligomer (PMO) in cell culture and dystrophic mdx mice. Improved exon-skipping efficiency of both 2′-OMePS and PMO was observed in the C2C12E50 cell line with all PEA polymers compared with PEI 25k or LF-2k. The degree of efficiency was found in the order of PEA 01, PEA 04 > PEA 05 > others. The in vivo study in mdx mice demonstrated enhanced exon-skipping of 2′-OMePS with the order of PEA 06 > PEA 04, PEA 07 > PEA 03 > PEA 01 > others, and much higher than PEI 25k formulated 2′-OMePS. Exon-skipping efficiency of PMO in formulation with the PEAs were significantly enhanced in the order of PEA 02 > PEA 10 > PEA 01, PEA 03 > PEA 05, PEA 07, PEA 08 > others, with PEA 02 reaching fourfold of Endo-porter formulated PMO. PEAs improve PMO delivery more effectively than 2′-OMePS delivery in vivo, and the systemic delivery evaluation further highlight the efficiency of PEA for PMO delivery in all skeletal muscle. The results suggest that the flexibility of PEA polymers could be explored for delivery of different AO chemistries, especially for antisense therapy. PMID:27483024

Impact of Pluronic F-68 vs Tween 80 on Fabrication and Evaluation of Acyclovir SLNs for Skin Delivery.

PubMed

Bhupinder, Kaur; Newton, Maria J

2016-01-01

The solid lipid nanoparticles (SLNs) of Acyclovir (ACV) were fabricated with Soya lecithin and Fractionated Coconut oil (medium chain glyceride) as a first time combination. The research was focused on developing ACV-SLN by using high pressure hot-homogenization technique. The ingredients were used in different concentrations and ratios to identify the best formulation design. The tween 80 and Pluronic F-68 were used in various concentrations in formulation design to assess the impact on the fabrication and evaluation of SLNs. The impact of nanotechnology gain to play a vital role in the topical pharmaceutical products and the related patents will play a significant role in related industries. The SLNs were subjected to various characterization techniques such as XRD, FTIR, Master sizer analysis and zeta potential. The mean particle size was determined by master sizer and zeta sizer. Transmission electron microscopy (TEM) was used as a tool to analyze the morphology and other features. The zeta potential and drug entrapment efficiency (EE%) were also determined for the prepared ACV-SLNs. The efficiency of drug release from prepared formulations was studied by using in vitro study with the utilization of dialysis membrane technique. SLN dispersions exhibited the average size in nano range. SLNs with small particle size found to have predetermined encapsulation efficiency, and relatively high loading capacity and predetermined in vitro drug release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of double emulsion nanoparticles for the encapsulation of bovine serum albumin.

PubMed

Martinez, Nelida Y; Andrade, Patricia F; Durán, Nelson; Cavalitto, Sebastian

2017-10-01

In the present work, a double emulsion was developed for the encapsulation of Bovine Serum Albumin (BSA) as a model protein for the future encapsulation of viral proteins. The first emulsion polydispersity index (PDI) was studied with increasing concentrations of poly (ε-caprolactone) (PCL) as stabilizer (from 16% w/v to 5% w/v) and polyvinyl alcohol (PVA) as the surfactant in the second emulsion at 1.5% w/v. Results suggest that at decreasing concentrations of PCL the PDI of the emulsion also decrease, indicating that viscosity of the emulsion is crucial in the homogeneity of the resultant size distribution of the nanoparticles. When PVA concentration in the second emulsion was increased from 1.5% w/v to 2.5% w/v the PDI also increased. To study the relationship between the structure of the surfactant in the second emulsion and the resultant BSA encapsulation, emulsions were prepared with Pluronic F68 and PVA both at 1.5% w/v and PCL in the first emulsion at 5% w/v. Results indicated that Pluronic F68 was a better stabilizer because at the same experimental conditions encapsulation of BSA was 1.5 higher than PVA. FTIR studies confirmed the presence of BSA in the nanoparticles. SEM and TEM microscopies showed a size distribution of 300nm-500nm size of nanoparticles. Circular dichroism studies demonstrated that the secondary structure of the protein was conserved after the encapsulation into the nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin.

PubMed

Chen, Ling-Chun; Chen, Yin-Chen; Su, Chia-Yu; Wong, Wan-Ping; Sheu, Ming-Thau; Ho, Hsiu-O

2016-11-16

Self-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of < 200 nm, an E.E. of >80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders.

Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin

PubMed Central

Chen, Ling-Chun; Chen, Yin-Chen; Su, Chia-Yu; Wong, Wan-Ping; Sheu, Ming-Thau; Ho, Hsiu-O

2016-01-01

Self-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of < 200 nm, an E.E. of >80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders. PMID:27848996

Evaluation of Pentravan®, Pentravan® Plus, Phytobase®, Lipovan® and Pluronic Lecithin Organogel for the transdermal administration of antiemetic drugs to treat chemotherapy-induced nausea and vomiting at the hospital.

PubMed

Bourdon, F; Lecoeur, M; Leconte, L; Ultré, V; Kouach, M; Odou, P; Vaccher, C; Foulon, C

2016-12-30

The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase ® , Lipovan ® , Pentravan ® , Pentravan ® Plus and Pluronic Lecithin Organogel (PLO)), for the compounding of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) and their administration in combination to treat chemotherapy-induced nausea and vomiting (CINV) at the hospital. Drugs were individually formulated in these vehicles and in mixture in Pentravan ® Plus using different penetration enhancers. Quality control of the forms has demonstrated that formulation process was mastered and convenient for the hospital (time required: 20min). Diffusion experiments through synthetic membranes and pig ear epidermis performed using Franz-type diffusion cells, have shown that the release and permeation process were greater for ondansetron than for dexamethasone and aprepitant, with a release step not limiting. As permeation of aprepitant was too low, it was discarded of the study. When ondansetron and dexamethasone were compounded in combination in Pentravan ® Plus, the most efficient vehicle, a permeation decrease was observed. Finally, the use of tween 20 instead of EtOH as chemical enhancer has led to 2-fold factor increase in the flux of dexamethasone, resulting in fluxes convenient for transdermal administration of ondansetron to a child, but insufficient for an adult and for dexamethasone. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural Changes in PEO-PPO-PEO Gels Induced by Methylparaben and Dexamethasone Observed Using Time-Resolved SAXS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meznarich, Norman A.K.; Juggernauth, K Anne; Batzli, Kiersten M

2011-11-17

Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) triblock copolymers (commercially available as Pluronic surfactants) micellize and structurally arrange into cubic quasicrystalline lattices as their temperature is raised. This structural evolution is seen macroscopically as a gelation, and the presence of these ordered phases can be controlled through both polymer concentration and temperature. The presence of added solutes within the dispersions can also affect the onset and kinetics of structure formation. Here we investigate the structures formed in Pluronic F127 solutions ranging from 20 to 30% with two pharmaceutical additives [methylparaben (MP) and dexamethasone (DX)] using small-angle X-ray scattering (SAXS). We observe bothmore » the progressive evolution and breakdown of these structures as the temperature is increased from 0 to 80 °C. Additionally, we conducted time-resolved SAXS measurements to elucidate the kinetics of the structural evolution. On the basis of the evolution of scattering peaks as the samples were being heated, we suggest that added MP changes the nucleation behavior of fcc phases within the sample from a heterogeneous process to a more homogeneous distribution of nucleated species. MP and DX also stabilize the micelle lattices, allowing them to persevere at higher temperatures. We observed the unusual result that the presence of DX caused the primary peaks of the structure factor to be suppressed, while preserving the higher order peaks. The primary peaks reappeared at the highest temperatures tested.« less

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

PubMed Central

Tang, Xiang-Jun; Huang, Kuan-Ming; Gui, Hui; Wang, Jun-Jie; Lu, Jun-Ti; Dai, Long-Jun; Zhang, Li; Wang, Gang

2016-01-01

As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells. PMID:27757032

Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer.

PubMed

Jeong, Keunsoo; Park, Solji; Lee, Yong-Deok; Kang, Chi Soo; Kim, Hyun Jun; Park, Hyeonjong; Kwon, Ick Chan; Kim, Jungahn; Park, Chong Rae; Kim, Sehoon

2016-08-01

Current approaches in use of water-insoluble photosensitizers for photodynamic therapy (PDT) of cancer often demand a nano-delivery system. Here, we report a photosensitizer-loaded biocompatible nano-delivery formulation (PPaN-20) whose size was engineered to ca. 20nm to offer improved cell/tissue penetration and efficient generation of cytotoxic singlet oxygen. PPaN-20 was fabricated through the physical assembly of all biocompatible constituents: pyropheophorbide-a (PPa, water-insoluble photosensitizer), polycaprolactone (PCL, hydrophobic/biodegradable polymer), and Pluronic F-68 (clinically approved polymeric surfactant). Repeated microemulsification/evaporation method resulted in a fine colloidal dispersion of PPaN-20 in water, where the particulate PCL matrix containing well-dispersed PPa molecules inside was stabilized by the Pluronic corona. Compared to a control sample of large-sized nanoparticles (PPaN-200) prepared by a conventional solvent displacement method, PPaN-20 revealed optimal singlet oxygen generation and efficient cellular uptake by virtue of the suitably engineered size and constitution, leading to high in vitro phototoxicity against cancer cells. Upon administration to tumor-bearing mice by peritumoral route, PPaN-20 showed efficient tumor accumulation by the enhanced cell/tissue penetration evidenced by in vivo near-infrared fluorescence imaging. The in vivo PDT treatment with peritumorally administrated PPaN-20 showed significantly enhanced suppression of tumor growth compared to the control group, demonstrating great potential as a biocompatible photosensitizing agent for locoregional PDT treatment of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays.

PubMed

Othman, Rahimah; Vladisavljević, Goran T; Simone, Elena; Nagy, Zoltan K; Holdich, Richard G

2017-12-06

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7-34 μm and was controlled by the PRX concentration in the feed solution (15-25 g L -1 ), antisolvent/solvent volume ratio (5-30), and type of antisolvent (Milli-Q water or 0.1-0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L -1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.

Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin

NASA Astrophysics Data System (ADS)

Chen, Ling-Chun; Chen, Yin-Chen; Su, Chia-Yu; Wong, Wan-Ping; Sheu, Ming-Thau; Ho, Hsiu-O.

2016-11-01

Self-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of < 200 nm, an E.E. of >80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders.

Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy

PubMed Central

Yallapu, Murali M.; Othman, Shadi F.; Curtis, Evan T.; Gupta, Brij K.; Jaggi, Meena; Chauhan, Subhash C.

2010-01-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapuetic agent for cancer therapy. PMID:21167595

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Gupta, Brij K; Jaggi, Meena; Chauhan, Subhash C

2011-03-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

Dual sustained release delivery system for multiple route therapy of an antiviral drug.

PubMed

Ramyadevi, D; Sandhya, P

2014-06-01

The first successful molecule against herpes infections was Acyclovir, which competes with new generations in the market, with its potential activity. The major physicochemical constraints and pharmacokinetics of Acyclovir such as low solubility, poor permeability, less half-life, high dose has initiated many researchers to develop diverse modified release dosage forms. The objective of this work was to design polymeric nanoparticles of Acyclovir and then incorporate the drug-loaded nanoparticles within an in situ gelling system to provide dual sustained release effect, whereby the duration of action and bioavailability through different routes of administration could be improved. The formulation was designed through 3(2) factorial design, first developing the nanoparticles using Polycaprolactone and Pluronic F127 by Solvent evaporation process, followed by dispersion of the suspended nanoparticles into thermosensitive in situ gelling system of Pluronic F127 with Carbopol. The characterization of the nanoparticles and its sol-gel system performed through zeta sizer, SEM, XRD, TG-DSC, FTIR and rheology helped to optimize the formulation. The drug release could be sustained to 60% and 30% at eight hours, for the nanoparticles and their in situ gel systems, respectively, with non-Fickian diffusion mechanism of drug release. The test for % cell viability with NIH3T3 cell line revealed low level of toxicity for the nanoparticles. The statistical significance obtained for the trail formulations experimentally proved its suitability for this dosage form design to achieve desired level of drug release.

Optical Sensor based Chemical Modification as a Porous Cellulose Acetate Film and Its Application for Ethanol Sensor

NASA Astrophysics Data System (ADS)

Mulijani, S.; Iswantini, D.; Wicaksono, R.; Notriawan, D.

2018-03-01

A new approach to design and construction of an optical ethanol sensor has been developed by immobilizing a direct dye at a porous cellulosic polymer fllm. This sensor was fabricated by binding Nile Red to a cellulose acetate membrane that had previously been subjected to an exhaustive base hydrolysis. The prepared optical ethanol sensor was enhanced by adding pluronic as a porogen in the membrane. The addition of pluronic surfactant into cellulose acetate membrane increased the hydrophilic and porous properties of membrane. Advantageous features of the design include simple and easy of fabrication. Variable affecting sensor performance of dye concentration have been fully evaluated and optimized. The rapid response results from the porous structure of the polymeric support, which minimizes barriers to mass transport. Signal of optical sensor based on reaction of dye nile red over the membrane with ethanol and will produce the purple colored product. Result was obtained that maximum intensity of dye nile red reacted with alcohol is at 630-640 nm. Linear regression equation (r2), limit of detection, and limit of quantitation of membrane with 2% dye was 0.9625, 0.29%, and 0.97%. Performance of optical sensor was also evaluated through methanol, ethanol and propanol. This study was purposed to measure the polarity and selectivity of optic sensor toward the alcohol derivatives. Fluorescence intensity of optic sensor membrane for methanol 5%, ethanol 5% and propanol 5% was 15113.56, 16573.75 and 18495.97 respectively.

CELLULAR DISTRIBUTION STUDIES OF THE NITRIC OXIDE-GENERATING ANTINEOPLASTIC PRODRUG JS-K, FORMULATED IN PLURONIC P123 MICELLES

PubMed Central

Kaur, Imit; Terrazas, Moises; Kosak, Ken M.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

2014-01-01

Objective Nitric oxide (NO) possesses anti-tumor activity. It induces differentiation and apoptosis in acute myeloid leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small cell lung cancer, glioma and liver cancer. Using the Pluronic® P123 polymer, we have developed a micelle formulation for JS-K in order to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells. Methods We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions. Key findings Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed. Conclusions We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K’s anti-leukemic properties. PMID:23927471

Poly(vinyl benzoate) nanoparticles for molecular delivery: Studies on their preparation and in vitro properties.

PubMed

Labruère, Raphaël; Sicard, Renaud; Cormier, Ryan; Turos, Edward; West, Leigh

2010-12-01

The preparation and properties of poly(vinyl benzoate) nanoparticle suspensions as molecular carriers are described for the first time. These nanoparticles can be formed by nanoprecipitation of commercial poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring 200-250nm in diameter. These nanoparticles are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Pluronic F68 stabilizes the nanoparticle and also protects it from enzymatic degradation. Up to 1.6% by weight of a lipid-soluble molecule such as coumarin-6 can be introduced into the nanoparticle during nanoprecipitation, compared to a water-soluble compound (5(6)-carboxyfluorescein) which gave almost no loading. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC(50)>1000μg/mL) and primary bovine aortic endothelial cells (IC(50)>500μg/mL), and non-bactericidal against a selection of representative test microbes (MIC >250μg/mL). These properties suggest that the poly(vinyl benzoate) nanoparticles may be suitable carriers for molecular delivery of lipophilic small molecules such as pharmaceutical and imaging agents. Copyright © 2010. Published by Elsevier B.V.

Characterization of chlorophyll derivatives in micelles of polymeric surfactants aiming photodynamic applications

NASA Astrophysics Data System (ADS)

Gerola, Adriana Passarella; de Morais, Flavia Amanda Pedroso; Costa, Paulo Fernando A.; Kimura, Elza; Caetano, Wilker; Hioka, Noboru

2017-02-01

The spectrophotometric properties of chlorophylls' derivatives (Chls) formulated in the Pluronics® F-127 and P-123 were evaluated and the results have shown that the Chls were efficiently solubilized in these drug delivery systems as monomers. The relative location of the Chls in the Pluronics® was estimated from the Stokes shift and micropolarity of the micellar environment. Chls with phytyl chain were located in the micellar core, where the micropolarity is similar to ethanol, while phorbides' derivatives (without phytyl chain) were located in the outer shell of the micelle, i.e., more polar environment. In addition, the thermal stability of the micellar formulations was evaluated through electronic absorption, fluorescence emission and resonance light scattering with lowering the temperature. The Chls promote the stability of the micelles at temperatures below the Critical Micellar Temperature (CMT) of these surfactants. For F-127 formulations, the water molecules drive through inside the nano-structure at temperatures below the CMT, which increased the polarity of this microenvironment and directly affected the spectrophotometric properties of the Chls with phytyl chain. The properties of the micellar microenvironment of P-123, with more hydrophobic core due to the small PEO/PPO fraction, were less affected by lowering the temperature than for F-127. These results enable us to better understand the Chls behavior in micellar copolymers and allowed us to design new drug delivery system that maintains the photosensitizer's properties for photodynamic applications.

Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

PubMed

Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

2017-09-01

Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

PubMed

Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

2014-06-01

Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics. Copyright © 2014 Elsevier B.V. All rights reserved.

Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models.

PubMed

Juretić, Marina; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena; Hafner, Anita; Lovrić, Jasmina; Pepić, Ivan

2018-07-30

The objective of this study was to systematically investigate the effects of surface active ophthalmic excipients on the corneal permeation of ophthalmic drugs using in vitro (HCE-T cell-based model) and ex vivo (freshly excised porcine cornea) models. The permeation of four ophthalmic drugs (i.e., timolol maleate, chloramphenicol, diclofenac sodium and dexamethasone) across in vitro and ex vivo corneal models was evaluated in the absence and presence of four commonly used surface active ophthalmic excipients (i.e., Polysorbate 80, Tyloxapol, Cremophor® EL and Pluronic® F68). The concentration and self-aggregation-dependent effects of surface active ophthalmic excipients on ophthalmic drug permeability were studied from the concentration region where only dissolved monomer molecules of surface active ophthalmic excipients exist, as well as the concentration region in which aggregates of variable size and dispersion are spontaneously formed. Neither the surface active ophthalmic excipients nor the ophthalmic drugs at all concentrations that were tested significantly affected the barrier properties of both corneal models, as assessed by transepithelial electrical resistance (TEER) monitoring during the permeability experiments. The lowest concentration of all investigated surface active ophthalmic excipients did not significantly affect the ophthalmic drug permeability across both of the corneal models that were used. For three ophthalmic drugs (i.e., chloramphenicol, diclofenac sodium and dexamethasone), depressed in vitro and ex vivo permeability were observed in the concentration range of either Polysorbate 80, Tyloxapol, Cremophor® EL or Pluronic® F68, at which self-aggregation is detected. The effect was the most pronounced for Cremophor® EL (1 and 2%, w/V) and was the least pronounced for Pluronic® F68 (1%, w/V). However, all surface active ophthalmic excipients over the entire concentration range that was tested did not significantly affect the in vitro and ex vivo permeability of timolol maleate, which is the most hydrophilic ophthalmic drug that was investigated. The results of the dynamic light scattering measurements point to the association of ophthalmic drugs with self-aggregates of surface active ophthalmic excipients as the potential mechanism of the observed permeability-depressing effect of surface active ophthalmic excipients. A strong and statistically significant correlation was observed between in vitro and ex vivo permeability of ophthalmic drugs in the presence of surface active ophthalmic excipients, which indicates that the observed permeability-altering effects of surface active ophthalmic excipients were comparable and were mediated by the same mechanism in both corneal models. Copyright © 2018 Elsevier B.V. All rights reserved.

Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia.

PubMed

Cai, Zhen; Pan, Bo; Jiang, Haiyue; Zhang, Lixia

2015-06-01

To evaluate the efficiency of chondrogenesis of human adipose-derived stem cells (ADSCs) induced by auricular chondrocytes from microtia via subcutaneous co-graft in nude mice. Human ADSCs and auricular chondrocytes were mixed at the ratio of 7:3 and suspended in 0.2 ml of Pluronic F-127 (5.0 × 10(7) cells/ml), and injected into Balb/c nude mice as the experimental group (Exp group). The same quantity of auricular chondrocytes (Ctr.1 group) or ADSCs (Ctr.2 group) in 0.2 ml of Pluronic F-127 was set as positive and negative control groups. The mixture of auricular chondrocytes (1.5 × 10(7) cells/ml) in 0.2 ml of Pluronic F-127 was set as the low concentration of chondrocyte control group (Ctr.3). At 8 weeks after grafting, the newly generated tissue pellets were isolated for morphological examination, haematoxylin and eosin staining, toluidine blue staining and safranin O staining of glycosaminoglycan (GAG), Masson's trichrome staining and immunohistochemical staining of type II collagen, and Verhoeff-iron-hematoxylin staining of elastic fibers. GAG content was determined by Alcian blue colorimetric method, and mRNA expression of type II collagen and aggrecan were examined by real-time PCR. Cartilage-like tissue with a white translucent appearance and good elasticity was generated in the Exp and Ctr.1 groups. The tissue pellets in the Ctr.2 and Ctr.3 groups were much smaller than those in the Ctr.1 group. The mature cartilage lacunas could be observed in the Exp and Ctr.1 groups, while were rarely seen in the Ctr.3 group and not observed in the Ctr.2 group. The expression of cartilage-specific extracellular matrix such as type II collagen, GAG content, aggrecan, and elastic fibers in the Exp group was similar to that in the Ctr.1 group, whereas the expression of these extracellular matrix substances was significantly lower in the Ctr.2 and Ctr.3 groups (both P < 0.01). Auricular chondrocytes from microtia can efficiently promote the chondrogenic differentiation and chondrogenesis of ADSCs by co-grafting in vivo. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Adsorption of calcitonin to glass.

PubMed

Law, S L; Shih, C L

1999-02-01

Surface adsorption of calcitonin on soda lime silica glass was investigated. An attempt was also made to examine the effect of additives on the inhibition of calcitonin adsorption. Results showed that the adsorption isotherms were of the Langmuir and Freundlich type, depending on pH. Less adsorption was found for calcitonin at pH 4.3. The addition of nonionic surfactants such as Pluronic F68 and Tween 80 to the calcitonin solutions demonstrated inhibition of absorption and reduction of adsorption rate. The addition of chlorobutanol also showed the effect of minimizing adsorption.

Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

PubMed Central

2007-01-01

Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed. PMID:17896100

Test of Surfactant-Based Dermal Wound Cleansers on Sulfur Mustard-Exposed Human Keratinocytes in an In Vitro Wound Healing Model

DTIC Science & Technology

2008-11-01

21. Chuang AH, Runner R, Lapp C , Bhatt B, McPherson, III, JC. The effect of Pluronic F-68 on wound healing of periodontal ligament fibroblasts in low alcohol conditions. Ga J Sci 2005; 63:74. ...PAGES 19a. NAME OF RESPONSIBLE PERSON Claudia L. Henemyre-Harris a. REPORT UNCLASSIFIED b. ABSTRACT UNCLASSIFIED c . THIS PAGE UNCLASSIFIED...8217-dichlorodiethyl sulfide) reacts with nucleophilic sites such as DNA, proteins , and membrane components, and several mechanisms for damage have been suggested.1

Consortia for Improving Medicine with Innovation and Technology

DTIC Science & Technology

2016-12-01

solutions of Pluronic F127 that are moderately concentrated (15-30%, w/w) at room temperature exhibit thermal gelation at physiological temperatures, and... conducted in harvested and preserved swine neck samples collected from healthy animals. Necessary outcomes from this milestone include defining the...permission  to   conduct  this  study  in  the  3rd  quarter  of  2014.  We  also  completed  the  review  by   DoD  HRPO  and  received  the  permission  to

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays

PubMed Central

2017-01-01

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15–25 g L–1), antisolvent/solvent volume ratio (5–30), and type of antisolvent (Milli-Q water or 0.1–0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L–1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals. PMID:29234241

TiO2 Nanostructure Synthesized by Sol-Gel for Dye Sensitized Solar Cells as Renewable Energy Source

NASA Astrophysics Data System (ADS)

Ramelan, A. H.; Wahyuningsih, S.; Saputro, S.; Supriyanto, E.; Hanif, Q. A.

2017-02-01

The use of renewable materials as a constituent of a smart alternative energy such as the use of natural dyes for light harvesting needs to be developed. Synthesis of anatase titanium dioxide (TiO2) and fabrication Dye-Sensitized Solar Cell (DSSC) using dye-based of anthocyanin from purple sweet potato (Ipomoea batatas L.) as a photosensitizer had been done. Synthesis TiO2 through sol-gel process with the addition of triblock copolymer Pluronic F127 template was controlled at pH 3 whereas calcination was carried out at a temperature of 500 °C, 550 °C and 600 °C. The obtained TiO2 were analyzed by XRD, SAA, and SEM. The conclusion is anatase TiO2 obtained until annealing up to 600 °C. Self-assembly Pluronic F127 triblock copolymer capable of restraining the growth of TiO2 crystals. Retention growth of TiO2 mesoporous produces material character that can be used as builders photoanode DSSC with natural sensitizer anthocyanin from purple sweet potatoes. Based on the analysis of X-ray diffraction patterns and surface area analyser, the higher the calcination temperature the greater the size of the anatase crystals is obtained, however, the smaller its surface area. Purple sweet potato anthocyanin’s dyed on to TiO2 was obtained a good enough performance for DSSC’s and gain the optimum performance from DSSC’s system built with mesoporous TiO2 annealed 550 °C using flavylium form anthocyanin.

Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation

PubMed Central

Liu, Yuling; Fu, Sai; Lin, Longfei; Cao, Yuhong; Xie, Xi; Yu, Hua; Chen, Meiwan; Li, Hui

2017-01-01

Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery. PMID:28435248

Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice

PubMed Central

Blankenship-Paris, Terry L.; Dutton, John W.; Goulding, David R.; McGee, Christopher A.; Kissling, Grace E.; Myers, Page H.

2016-01-01

Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic® F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID:27654688

Molecular Level Understanding of Sodium Dodecyl Sulfate (SDS) Induced Sol-Gel Transition of Pluronic F127 Using Fisetin as a Fluorescent Molecular Probe.

PubMed

Mishra, Jhili; Swain, Jitendriya; Mishra, Ashok Kumar

2018-01-11

The thermoreversible sol-gel transition of pluronic F127 is markedly altered even with addition of submicellar concentration of sodium dodecyl sulfate (SDS) surfactant. Multiple fluorescence parameters like fluorescence intensity, fluorescence anisotropy and fluorescence lifetime of both the prototropic forms (anion (A - *) and phototautomer FT*) of the photoprototropic fluorescent probe fisetin has been efficiently used to understand the molecular level properties like polarity and microviscosity of the PF127-SDS system as a function of temperature. The SDS-induced increase in the interfacial hydrophobicity level is seen to affect the sol-gel phase transition of PF127 (21-18 °C). The E T (30) polarity parameter value of anionic emission of fisetin suggests that there is a considerable decrease in the polarity of the PF127 medium with increase in temperature and with the addition of SDS. The microviscosity progressively increases from ∼5 mPa s (sol state, 10 °C) to ∼22.01 mPa s (gel state 35 °C) in aqueous solution of PF127. The variation in microviscosity with addition of SDS in PF127-SDS mixed system is significant in sol phase whereas in gel phase this variation is significantly less. Temperature dependent fluorescence lifetime of FT* indicates that there is heterogeneity in distribution of fisetin molecules at different domains of PF127. This work also show-cases the sensitivity of fisetin toward change in polarity and change in sol-gel transition temperature of copolymer PF127 with variation in temperature (both forward and reverse directions) and SDS.

Ga[OSi(O(t)Bu)3]3·THF, a thermolytic molecular precursor for high surface area gallium-containing silica materials of controlled dispersion and stoichiometry.

PubMed

Dombrowski, James P; Johnson, Gregory R; Bell, Alexis T; Tilley, T Don

2016-07-05

The molecular precursor tris[(tri-tert-butoxy)siloxy]gallium, as the tetrahydrofuran adduct Ga[OSi(O(t)Bu)3]3·THF (), was synthesized via the salt metathesis reaction of gallium trichloride with NaOSi(O(t)Bu)3. This complex serves as a model for isolated gallium in a silica framework. Complex decomposes thermally in hydrocarbon solvent, eliminating isobutylene, water, and tert-butanol to generate high surface area gallium-containing silica at low temperatures. When thermal decomposition was performed in the presence of P-123 Pluronic as a templating agent the generated material displayed uniform vermicular pores. Textural mesoporosity was evident in untemplated material. Co-thermolysis of with HOSi(O(t)Bu)3 in the presence of P-123 Pluronic led to materials with Ga : Si ratios ranging from 1 : 3 to 1 : 50, denoted UCB1-GaSi3, UCB1-GaSi10, UCB1-GaSi20 and UCB1-GaSi50. After calcination at 500 °C these materials exhibited decreasing surface areas and broadening pore distributions with increasing silicon content, indicating a loss of template effects. The position and dispersion of the gallium in UCB1-GaSi materials was investigated using (71)Ga MAS-NMR, powder XRD, and STEM/EDS elemental mapping. The results indicate a high degree of gallium dispersion in all samples, with gallium oxide clusters or oligomers present at higher gallium content.

Intracerebral Cell Implantation: Preparation and Characterization of Cell Suspensions.

PubMed

Rossetti, Tiziana; Nicholls, Francesca; Modo, Michel

2016-01-01

Intracerebral cell transplantation is increasingly finding a clinical translation. However, the number of cells surviving after implantation is low (5-10%) compared to the number of cells injected. Although significant efforts have been made with regard to the investigation of apoptosis of cells after implantation, very little optimization of cell preparation and administration has been undertaken. Moreover, there is a general neglect of the biophysical aspects of cell injection. Cell transplantation can only be an efficient therapeutic approach if an optimal transfer of cells from the dish to the brain can be ensured. We therefore focused on the in vitro aspects of cell preparation of a clinical-grade human neural stem cell (NSC) line for intracerebral cell implantation. NSCs were suspended in five different vehicles: phosphate-buffered saline (PBS), Dulbecco's modified Eagle medium (DMEM), artificial cerebral spinal fluid (aCSF), HypoThermosol, and Pluronic. Suspension accuracy, consistency, and cell settling were determined for different cell volume fractions in addition to cell viability, cell membrane damage, and clumping. Maintenance of cells in suspension was evaluated while being stored for 8 h on ice, at room temperature, or physiological normothermia. Significant differences between suspension vehicles and cellular volume fractions were evident. HypoThermosol and Pluronic performed best, with PBS, aCSF, and DMEM exhibiting less consistency, especially in maintaining a suspension and preserving viability under different storage conditions. These results provide the basis to further investigate these preparation parameters during the intracerebral delivery of NSCs to provide an optimized delivery process that can ensure an efficient clinical translation.

Formulation development and evaluation of innovative two-polymer (SR-2P) bioadhesive vaginal gel.

PubMed

Podaralla, Satheesh; Alt, Carsten; Shankar, Gita N

2014-08-01

The main objective of this investigation was to study the feasibility of developing a vaginal bioadhesive microbicide using a SRI's proprietary two-polymer gel platform (SR-2P). Several formulations were prepared with different combinations of temperature-sensitive polymer (Pluronic® F-127) and mucoadhesive polymer (Noveon® AA-1), producing gels of different characteristics. Prototype polymeric gels were evaluated for pH, osmolality, buffering capacity, and viscosity under simulated vaginal semen dilutions, and bioadhesivity using ex vivo mini pig vaginal tissues and texture analyzer. The pH of the polymeric gel formulations ranged from 5.1 to 6.4; the osmolality varied from 13 to 173 mOsm. Absolute viscosity ranged from 513 to 3,780 cPs, and was significantly reduced (1.5- to 3-fold) upon incubation with simulated vaginal and semen fluid mixture. Among the tested gels (indicated in the middle row as a molar ratio of a mixture of Noveon vs. Pluronic), only SR-2P retained gel structure upon dilution with simulated fluids and mild simulated coital stress. The pH of the SR-2P gel was maintained at about 4.6 in simulated vaginal fluid and also showed high peak force of adhesion in mini pig vaginal tissue. Furthermore, SR-2P gel caused no or only minimal irritation in a mouse vaginal irritation model. The results of this preliminary study demonstrated the potential application of SR-2P gel as a vaginal microbicide vehicle for delivery of anti-HIV agents.

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies.

PubMed

Nour, Samia A; Abdelmalak, Nevine S; Naguib, Marianne J; Rashed, Hassan M; Ibrahim, Ahmed B

2016-11-01

Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

Treatment of skin injuries induced by sulfur mustard with calmodulin antagonists, using the pig model.

PubMed

Kadar, T; Fishbeine, E; Meshulam, Y; Sahar, R; Chapman, S; Liani, H; Barness, I; Amir, A

2000-12-01

Sulfur mustard (HD) is a potent cutaneous vesicant that penetrates rapidly through the skin, causing prolonged injuries and leading to severe incapacitation. Although there has been long and intensive efforts to find a treatment for HD skin lesions, no effective treatment is available for HD-induced skin injuries. Recently, ointments containing calmodulin antagonists were found to be effective in preventing skin injuries induced by HD in hairless mice. The present study was designed to investigate the beneficial effects of topical treatments with calmodulin antagonists against HD skin lesions in the pig model. The pig is used as a preferred animal model for human skin in many studies, including vesicants. Neat HD, either in liquid form (0.2-1 microl droplets) or as vapour, was applied to the back skin of female pigs (a cross Large White & Landrace, 10-12 kg) for various exposure durations. Evaluation was based on quantitative analysis of the degree of erythema and area of the lesions, as well as histological evaluation. Calmodulin antagonists (10% pentamide, 1% trifluoperazine, 2% thioridazine) and anaesthetics (20% lidocaine and 3% benoxinate) were dissolved in pluronic F-127 base according to Kim et al. (Eur. J. Pharmacol. 1996; 313: 107-114) or in saline, and were applied either topically as ointments or by intradermal injection, as early as 5 min post-exposure (twice a day for at least 3 days). The results demonstrated that topically applied pluronic base ointments containing lidocaine or pentamide produce beneficial effects when applied immediately after short-term HD exposure to pig skin.

Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type.

PubMed

Justo, Oselys Rodriguez; Simioni, Patricia Ucelli; Gabriel, Dirce Lima; Tamashiro, Wirla Maria da Silva Cunha; Rosa, Paulo de Tarso Vieira; Moraes, Ângela Maria

2015-10-29

Numerous plants from have been investigated due to their anti-inflammatory activity and, among then, extracts or components of ginger (Zingiber officinale Roscoe) and rosemary (Rosmarinus officinalis L.), sources of polyphenolic compounds. 6-gingerol from ginger rhizome and carnosic acid and carnosol from rosemary leaves present anti-tumor, anti-inflammatory and antioxidant activities. However, the evaluation of the mechanisms of action of these and other plant extracts is limited due to their high hydrophobicity. Dimethylsulfoxide (DMSO) is commonly used as a vehicle of liposoluble materials to mammalian cells in vitro, presenting enhanced cell penetration. Liposomes are also able to efficiently deliver agents to mammalian cells, being capable to incorporate in their structure not only hydrophobic molecules, but also hydrophilic and amphiphilic compounds. Another strategy is based on the use of Pluronic F-68, a biocompatible low-foaming, non-ionic surfactant, to disperse hydrophobic components. Here, these three delivery approaches were compared to analyze their influence on the in vitro anti-inflammatory effects of ginger and rosemary extracts, at different concentrations, on primary mammalian cells and on a tumor cell line. Ginger and rosemary extracts free of organic solvents were obtained by supercritical fluid extraction and dispersed in DMSO, Pluronic F-68 or liposomes, in variable concentrations. Cell viability, production of inflammatory mediators and nitric oxide (NO) release were measured in vitro on J774 cell line and murine macrophages primary culture stimulated with bacterial lipopolysaccharide and interferon-γ after being exposed or not to these extracts. Ginger and rosemary extracts obtained by supercritical CO2 extraction inhibited the production of pro-inflammatory cytokines and the release of NO by peritoneal macrophages and J774 cells. The delivery vehicles influenced the anti-inflammatory effects. Comparatively, the ginger extract showed the highest anti-inflammatory activity on the tumor cell line. Controversially, rosemary extract dispersed on DMSO induced a more significant IL-1 and TNF-α reduction than ginger extract in primary macrophages. Amongst the tested delivery vehicles, DMSO was the most suitable, presenting reduced cytotoxicity, followed by Pluronic F-68 and liposomes, provably due to differences in their form of absorption, distribution and cellular metabolism. Co-administration of liposomes and plant extracts may cause death of macrophages cells and induction of NO production. It can be concluded that some of the beneficial effects attributed to extracts of ginger and rosemary may be associated with the inhibition of inflammatory mediators due to their high antioxidant activity. However, these effects were influenced by the type of delivery vehicle.

Limited use of Centritech Lab II Centrifuge in perfusion culture of rCHO cells for the production of recombinant antibody.

PubMed

Kim, Byoung Jin; Oh, Duk Jae; Chang, Ho Nam

2008-01-01

Perfusion cultures of recombinant Chinese hamster ovary cells, producing recombinant antibody against the S surface antigen of Hepatitis B virus, were carried out in continuous and intermittent mode using a Centritech Lab II Centrifuge. In the continuous perfusion process, despite the absence of shear stress from the pump head, long-term operation was not possible because of continuously repeated exposure to oxygen limitation and low temperature, as well as shear stress from centrifugal force. In the intermittent perfusion processes, the frequency of cell-passage through the centrifuge was substantially reduced, compared with the continuous perfusion mode; however, the degree of reduction could not guarantee stable long-term operation. Although various operating parameters were applied in the intermittent perfusion cultures, high cell densities could not be maintained stably. In a single bioreactor culture system, a specific cell that is returned from the centrifuge to the bioreactor could be transferred from the bioreactor to the centrifuge again in the next cycle. These repetitive damages, caused by shear stress from the pump head and centrifugal force, as well as exposure to suboptimal conditions such as oxygen limitation and low temperature below 37 degrees C, were more serious at higher perfusion rates. Subsequently, damaged cells and dead cells were continuously accumulated in the bioreactor. Culture temperature shift from 37 to 33 degrees C increased antibody concentrations but showed inhibitory effects on cell growth. The negative effects of lowering culture temperature on cell growth overwhelmed the positive effects on antibody production. To protect cells from shear stress, Pluronic F-68 was 2-fold concentrated in the culture medium; nevertheless, a significantly higher concentration of Pluronic F-68 (2 g/L) may have inhibitory effects on cell growth.

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice.

PubMed

Li, Jianing; Wang, Yu; Tang, Lihua; de Villiers, Willem J S; Cohen, Donald; Woodward, Jerold; Finkelman, Fred D; Eckhardt, Erik R M

2013-02-01

The prevalence of peanut allergies is increasing. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCTs), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared with long-chain triglycerides (LCTs), which stimulate mesenteric lymph flow and are absorbed in chylomicrons through mesenteric lymph. We sought to test how dietary MCTs affect food allergy. C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured. MCT suppressed antigen absorption into blood but stimulated absorption into Peyer patches. A single gavage of peanut protein with MCT, as well as prolonged feeding in MCT-based diets, caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis on systemic challenge and IgE-dependent anaphylaxis on oral challenge. MCT feeding stimulated jejunal-epithelial thymic stromal lymphopoietin, Il25, and Il33 expression compared with that seen after LCT feeding and promoted T(H)2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared with challenges with the LCT. Importantly, the effects of MCTs could be mimicked by adding Pluronic L81 to LCTs, and in vitro assays indicated that chylomicrons prevent basophil activation. Dietary MCTs promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating T(H)2 responses. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Intracellular delivery of etoposide loaded biodegradable nanoparticles: cytotoxicity and cellular uptake studies.

PubMed

Yadav, Khushwant S; Jacob, Sheeba; Sachdeva, Geetanjali; Sawant, Krutika K

2011-08-01

The preferred delivery systems for anticancer drugs would be the one which would have selective and effective destruction of cancer cells. In the present study etoposide (ETO) loaded nanoparticles (NP) were prepared using PLGA (ETO-PLGA NP), PLGA-MPEG block copolymer (ETO-PLGA-MPEG NP) and PLGA-Pluronic copolymer (ETO-PLGA-PLU NP) and they were evaluated for cytotoxicity and cellular uptake studies using two cancer cell lines, L1210 and DU145. The IC50 values for L1210 cells were 18.0, 6.2, 4.8 and 5.4 microM and for DU145 cells the IC50 values were 98.4, 75.1, 60.1 and 71.3 microM for ETO, ETO-PLGA NP, ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP respectively. The increased cytotoxicities were attributed to increased uptake of the NPs by the cells. Moreover the ETO loaded PLGA-MPEG NP and PLGA-Pluronic NP showed a sustained cytotoxic effect till 5 days on both the cell lines. Results of the long term cytotoxicity study concluded that the drug loaded PLGA nanoparticulate formulations were efficient in decreasing the viability of the L1210 cells over a period of three days, whereas the pure drug exerted its maximum efficiency on the day one itself. Z-stack confocal images of NPs showed fluorescence activity in each section of DU 145 and L1210 cells indicating that the nanoparticles were internalized by the cells. The study concluded that ETO loaded PLGA NPs had higher cytotoxicity compared with that of the free drug and ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP had higher cell uptake efficiency compared with that of ETO-PLGA NP. The developed PLGA based NPs shows promise to be used for cancer therapy.

Effects of alcohol ethoxylate and pluronic detergents on the development of pasture bloat in cattle and sheep.

PubMed

Stanford, K; Wang, Y; Berg, B P; Majak, W; McCartney, D H; Baron, V; McAllister, T A

2001-01-01

A series of studies was conducted to determine the efficacy and possible modes of action of a water-soluble mixture of alcohol ethoxylate and pluronic detergents (AEPD; Blocare 4511, ANCARE, Auckland, NZ) in preventing pasture bloat in ruminants grazing or fed freshly harvested alfalfa. Ten cannulated Suffolk wethers were offered freshly harvested alfalfa; five were given a daily intraruminal dose of 40 ml of 50% AEPD (vol/vol) 1 h before feeding, and five (controls) were dosed with water. Viscosity of ruminal fluid was reduced (P < 0.001) in AEPD-treated wethers, relative to the controls, for the first 2 h after feeding but not at 4 h after feeding and beyond. Treatment with AEPD did not affect dry matter (DM) intake, digestibility of DM, acid detergent fiber, or neutral detergent fiber, or N digestion and retention, implying that AEPD likely would not affect milk production. In a crossover grazing study, five of the wethers were given AEPD in drinking water (0.1%, vol/vol); treatment with AEPD was 100% effective for preventing bloat in sheep grazing early-bloom alfalfa for 4 h daily. Replicate grazing studies were conducted with cattle in Lethbridge, AB; Lacombe, AB; and Kamloops, BC. Treated animals received AEPD in the water (0.06%, vol/vol) and grazed vegetative alfalfa for 6 h daily. As it did with sheep, AEPD treatment effectively precluded the bloat observed in control animals. Consequently, AEPD may be a valuable tool for alfalfa pasture-based dairy production although further study is required to develop an integrated model for optimal administration under a variety of climatic conditions.

Highly efficient photodynamic therapy colloidal system based on chloroaluminum phthalocyanine/pluronic micelles.

PubMed

Py-Daniel, Karen R; Namban, Joy S; de Andrade, Laise R; de Souza, Paulo E N; Paterno, Leonardo G; Azevedo, Ricardo B; Soler, Maria A G

2016-06-01

Phthalocyanine derivatives comprise the second generation of photosensitizer molecules employed in photodynamic therapy (PDT) and have attracted much attention due to their outstanding photosensitizing performance. Most phthalocyanines are hydrophobic compounds that require association to drug delivery systems for clinical use. In this study, formulations of Pluronic F127 micelles incorporated with chloroaluminum phthalocyanine, or else F127/AlClPc, were produced at optimized conditions aiming at efficient and biocompatible PDT colloidal systems. Absorption/emission spectroscopies, as well as dynamic light scattering were performed to evaluate the optimum conditions for the F127 micelle formation and AlClPc incorporation. The micelles formation was attained with F127 concentrations ranging from 50 to 150mgmL(-1). At these conditions, AlClPc photosensitizer molecules were encapsulated into the hydrophobic micelle core and, therefore, readily solubilized in physiological medium (PBS pH 7.2). Encapsulation efficiency of about 90% resulted from different AlClPc concentrations. Identification of singlet oxygen production by irradiated F127/AlClPc formulations indicated good applicability for PDT. In vitro tests conducted with A549 human lung carcinoma cell line incubated with the F127/AlClPc formulations, at different AlClPc loadings, followed by only 18min of light irradiation (660nm LED, fluence of 25.3J/cm(2)), showed a cellular damage as high as 90% for rather low dosages of AlClPc (0.1-5.0μgmL(-1)). Further, no cytotoxicity occurred on non-irradiated cells. These findings suggest those F127/AlClPc formulations are highly promising for PDT applications, since they are easily prepared and the incubation and irradiation times are significantly shortened. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

PubMed

Loh, Zhiao C; Elkordy, Amal A

2015-01-01

The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.

Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

PubMed

Xiong, Xiang Yuan; Pan, Xiaoqian; Tao, Long; Cheng, Feng; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

2017-10-01

Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.5%) was highest in the mass ratio 5 to 3 of FA-F87-PLA to TPGS. The in vitro cytotoxicity assays indicated that the IC50 values for free PTX injections, PTX-loaded FA-F87-PLA micelles and PTX-loaded FA-F87-PLA/TPGS mixed micelles after 72h of incubation were 1.52, 0.42 and 0.037mg/L, respectively. The quantitative cellular uptake of coumarin 6-loaded FA-F87-PLA/TPGS and FA-F87-PLA micelles showed that the cellular uptake efficiency of mixed micelles was higher for 2 and 4h incubation, respectively. In vivo pharmacokinetic studies found that the AUC of PTX-loaded FA-F87-PLA/TPGS mixed micelles is almost 1.4 times of that of PTX-loaded FA-F87-PLA micelles. The decreased particle size and inhibition of P-glycoprotein effect induced by the addition of TPGS could result in enhancing the cellular uptake and improving the antitumor efficiency of PTX-loaded FA-F87-PLA/TPGS mixed micelles. Copyright © 2017 Elsevier B.V. All rights reserved.

Spontaneous temperature-sensitive Pluronic(®) based niosomes: Triggered drug release using mild hyperthermia.

PubMed

Tavano, Lorena; Oliviero Rossi, Cesare; Picci, Nevio; Muzzalupo, Rita

2016-09-25

Inclusion of lipids or polymers with a transition temperature closer to physiological body temperature (40-42°C) is a strategy used in tumor therapy for more than 30 years, because it allows induction of drug release from delivery systems by mild hyperthermia. Unfortunately, most of these thermo-sensitive carriers are removed from circulation before completion of their function. Thus, novel multi-functional niosomes possessing spontaneous stealth and thermo-sensitive properties were developed from L64 Pluronic(®) and L64ox as its derivative, in presence or absence of cholesterol. The use of L64 both as amphiphilic constituent and thermo-sensitive molecule, gave the possibility to bypass the use of additional excipients and increased the system biocompatibility. Niosomes diameter ranged from 400 to 750nm and were long term stable. Calcein and 5-FU possess great affinity to niosomal matrices rich in PEO groups. Negative Z-potential values were attributed to the negative charges onto the niosomes surface and generally change according to the temperature. The in vitro drugs release studies were performed at 25°C, 37°C and 42°C, that are representative of certain conditions (storage, physiological condition and mild hyperthermia, respectively). Results showed that L64-based niosomes possess spontaneous thermo-sensitive properties: drugs releases were found to be more pronounced at 42°C. These early results are a promising first step for the development of multi-functional devices that combine several advantages such as stealth properties and temperature controllability at the desired location and time, for a more specific and efficient pharmacological therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler.

PubMed

Singh, Deepak J; Jain, Rajesh R; Soni, P S; Abdul, Samad; Darshana, Hegde; Gaikwad, Rajiv V; Menon, Mala D

2015-08-01

Dry powder inhalers (DPI) are generally formulated by mixing micronized drug particles with coarse lactose carrier particles to assist powder handling during the manufacturing and powder aerosol delivery during patient use. In the present study, surface modified lactose (SML) particles were produced using force control agents, and their in vitro performance on dry powder inhaler (DPI) formulation of Fluticasone propionate was studied. With a view to reduce surface passivation of high surface free energy sites on the most commonly used DPI carrier, α- lactose monohydrate, effects of various force control agents such as Pluronic F-68, Cremophor RH 40, glyceryl monostearate, polyethylene glycol 6000, magnesium stearate, and soya lecithin were studied. DPI formulations prepared with SML showed improved flow properties, and atomic force microscopy (AFM) studies revealed decrease in surface roughness. The DSC and X-ray diffraction patterns of SML showed no change in the crystal structure and thermal behavior under the experimental conditions. The fine particle fraction (FPF) values of lactose modified with Pluronic F-68, Cremophor RH 40, glyceryl monostearate were improved, with increase in concentration up to 0.5%. Soya lecithin and PEG 6000 modified lactose showed decrease in FPF value with increase in concentration. Increase in FPF value was observed with increasing concentration of magnesium stearate. Two different DPI devices, Rotahaler(®) and Diskhaler(®), were compared to evaluate the performance of SML formulations. FPF value of all SML formulations were higher using both devices as compared to the same formulations prepared using untreated lactose. One month stability of SML formulations at 40°C/75% RH, in permeable polystyrene tubes did not reveal any significant changes in FPF values. SML particles can help in reducing product development hindrances and improve inhalational properties of DPI.

Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation.

PubMed

Soliman, Ghareb M; Fetih, Gihan; Abbas, Ahmed M

2017-03-01

The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness. Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic ® (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (T sol-gel ), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725). The T sol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28-37 °C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration. Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

Nootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration.

PubMed

Park, Jeongmin; Choi, Eunshil; Shin, Seulgi; Lim, Sungsu; Kim, Dohee; Baek, Suji; Lee, Kang Pa; Lee, Jae Jun; Lee, Byeong Han; Kim, Bokyung; Jeong, Keunsoo; Baik, Ja-Hyun; Kim, Yun Kyung; Kim, Sehoon

2018-06-15

Traumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration. MB was formulated via electrostatically/hydrophobically directed assembly with fatty acid and Pluronic surfactant (F-127 or F-68) to construct nanocomplexes of two different colloidal sizes (<10 nm and ~108 nm in hydrodynamic diameter for NanoMB-127 and NanoMB-68, respectively). Compared to uncomplexed free MB, formulation into the ultrasmall nanocomplex (NanoMB-127) significantly enhanced the uptake of MB by blood-brain vascular endothelial bEnd3 cells in vitro, and indeed improved its BBB penetration upon systemic administration to normal mice in vivo. However, large-size NanoMB-68 showed negligible BBB crossing despite the efficient bEnd3 cell internalization in vitro, probably due to the unfavorable pharmacokinetic profile associated with its large particle size. By virtue of the efficient BBB penetration and cellular uptake, ultrasmall NanoMB-127 was shown to distinctively reduce the expression level of an inflammatory cytokine with no notable toxicity in vitro and also considerably prevent the neurodegeneration after TBI in mice at much lower doses than free MB. Overall, the Pluronic-supported nanocomplexation method allows efficient brain delivery of MB, offering a novel way of enhancing the efficacy of neurotherapeutics to treat brain diseases. Copyright © 2018. Published by Elsevier B.V.

In Situ GISAXS investigation of low-temperature aging in oriented surfactant-mesostructured titania thin films

DOE PAGES

Nagpure, Suraj; Das, Saikat; Garlapalli, Ravinder K.; ...

2015-09-11

In this study, the mechanism of forming orthogonally oriented hexagonal close packed (o-HCP) mesostructures during aging of surfactant-templated titania thin films is elucidated using in situ grazing incidence small-angle x-ray scattering (GISAXS) in a controlled-environment chamber. To promote orthogonal orientation, glass slides are modified with crosslinked Pluronic P123, to provide surfaces chemically neutral towards both blocks of mesophase template P123. At 4 °C and 80% RH, the o-HCP mesophase emerges in thin (~60 nm) films by a direct disorder-to-order transition, with no intermediate ordered mesophase. The Pluronic/titania o-HCP GISAXS intensity emerges only after ~10-12 minutes, much slower than previously reportedmore » for smallmolecule surfactants. The Avrami model applied to the data suggests 2D growth with nucleation at the start of the process with a half-life of 39.7 minutes for the aging time just after the induction period of 7 minutes followed by a period consistent with 1D growth kinetics. Surprisingly, films that are thicker (~250 nm) or cast on unmodified slides form o-HCP mesophase domains, but by a different mechanism (2D growth with continuous nucleation) with faster and less complete orthogonal alignment. Thus, the o-HCP mesophase is favored not only 2 by modifying the substrate, but also by aging at 4 °C, which is below the lower consolute temperature (LCST) of the poly(propylene oxide) block of P123. Consistent with this, in situ GISAXS shows that films aged at room temperature (above the LCST of the PPO block) have randomly oriented HCP mesostructure.« less

Aripiprazole-Loaded Polymeric Micelles: Fabrication, Optimization and Evaluation using Response Surface Method.

PubMed

Patil, Payal Hasmukhlal; Wankhede, Pooja R; Mahajan, H S; Zawar, Laxmikant

2018-01-04

The fundamental objective of current study was to encapsulate Ari-piprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Ar-ipiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer. The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles. The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, −4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20 hrs which were found about thrice as compared to that of pure drug. The optimized ARP micellar for-mulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Trans-formed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study. It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hierarchical porous silver metal using Pluronic F-127 and graphene oxide as reinforcing agents for the reduction of o-nitroaniline to 1, 2-benzenediamine

NASA Astrophysics Data System (ADS)

Bano, Mustri; Ahirwar, Devendra; Thomas, Molly; Sheikh, Mehraj Ud Din; Khan, Farid

2017-04-01

An elegant method is used to prepare silver monoliths with Pluronic F-127(F-127) as sacrificial template by modified sol-gel method. Si nanoparticles (SiNPs) and graphene oxide (GO) are added in situ to Ag/F-127 hydrogel for the reduction of ο-nitroaniline (ο-NA) to 1, 2-benzenediamine. Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric analysis (TGA), Raman Spectroscopy, Powder X-Ray Diffraction (PXRD) analysis and Brunauer-Emmett-Teller (BET) Nitrogen adsorption techniques were used for characterization of monoliths. An epoch-making catalytic activity of Ag/F-127/GO monoliths is observed in the reduction of ο-NA to 1, 2-benzenediamine in presence of NaBH4 in aqueous media. The catalyst Ag/F-127/GO took only 2 min which is the minimum time reported so far with significant rate constant claimed itself a leading catalyst for the reduction of ο-NA to 1,2-benzenediamine. Pseudo first order rate constant (k) and Turn over frequency (TOF) values are 0.231 min-1 and 30.053×1019 molecules min-1 respectively suggest that the catalyst has industrial importance. Recyclability and stability of Ag/F-127/GO catalyst are studied successfully up to 10 cycles. Energy of activation (Ea), and thermodynamic parameters viz. activation enthalpy (ΔH≠), activation Gibbs free energy (ΔG≠), and entropy of activation (ΔS≠) were also ascertained. Catalytic activities of Ag/F-127, Ag/F-127/Dextran, Ag/F-127/Trimethylbenzene (TMB), Ag/F-127/SiNPs, and Ag/F-127/Si/GO monoliths were also studied.

Rapid photogeneration of silver nanoparticles in ethanolic solution: a kinetic study.

PubMed

Yahyaei, Bahareh; Azizian, Saeid

2013-01-15

Ag nanoparticles have been synthesized via UV irradiation of ethanolic solution of AgNO3 in presence of pluronic F127 surfactant. This study is aimed at developing a rapid, simple and green method to prepare Ag nanoparticles and understanding its generation kinetics. The formation dependency of silver nanoparticles on the concentration of reactants, UV exposure time and temperature has been investigated by using UV-vis spectroscopy. The 2D map technique has been used for the first time to estimate the switching time between the nucleation and growth of Ag nanoparticles. Appropriate kinetic models were used for modelling of both stages. Copyright © 2012 Elsevier B.V. All rights reserved.

Ordered mesoporous ternary mixed oxide materials as potential adsorbent of biomolecules

NASA Astrophysics Data System (ADS)

Pal, Nabanita; Bhaumik, Asim

2012-05-01

Designing a suitable mesoporous framework material for the selective adsorption or immobilization of biomolecules is a very challenging area of research. Mesoporous ternary Co-Si-Al oxide materials with large mesopore and their nanoscale ordering have been reported. The synthesis of these ternary oxides are accomplished through evaporation induced self-assembly (EISA) method using Pluronic non-ionic surfactant F127 under non-aqueous sol-gel route. N2 sorption study revealed high BET surface areas for these materials. These materials exhibited very efficient and selective adsorption for the essential biomolecules like vitamin C (ascorbic acid), vitamin B6 (pyridoxine) and vitamin B3 (nicotinic acid) from their respective aqueous solutions.

Profiling plasma extracellular vesicle by pluronic block-copolymer based enrichment method unveils features associated with breast cancer aggression, metastasis and invasion

PubMed Central

Rosenow, Matthew; Xiao, Nick; Spetzler, David

2018-01-01

ABSTRACT Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects. However, the selectivity of the precipitation becomes critical. Here, we present a simple plasma EV enrichment protocol based on pluronic block copolymer. The enriched plasma EV was able to be verified by multiple platforms. Our results showed that the particles enriched from plasma by the copolymer were EV size vesicles with membrane structure; proteomic profiling showed that EV-related proteins were significantly enriched, while high-abundant plasma proteins were significantly reduced in comparison to other precipitation-based enrichment methods. Next-generation sequencing confirmed the existence of various RNA species that have been observed in EVs from previous studies. Small RNA sequencing showed enriched species compared to the corresponding plasma. Moreover, plasma EVs enriched from 20 advanced breast cancer patients and 20 age-matched non-cancer controls were profiled by semi-quantitative mass spectrometry. Protein features were further screened by EV proteomic profiles generated from four breast cancer cell lines, and then selected in cross-validation models. A total of 60 protein features that highly contributed in model prediction were identified. Interestingly, a large portion of these features were associated with breast cancer aggression, metastasis as well as invasion, consistent with the advanced clinical stage of the patients. In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity and it might be suitable for larger-scale discovery studies. PMID:29696079

Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

PubMed

Pawar, Atmaram; Singh, Srishti; Rajalakshmi, S; Shaikh, Karimunnisa; Bothiraja, C

2018-01-15

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Interlaboratory validation of 1% pluronic l92 surfactant as a suitable, aqueous vehicle for testing pesticide formulations using the murine local lymph node assay.

PubMed

Boverhof, Darrell R; Wiescinski, Connie M; Botham, Phil; Lees, David; Debruyne, Eric; Repetto-Larsay, Marina; Ladics, Gregory; Hoban, Denise; Gamer, Armin; Remmele, Marina; Wang-Fan, Weizheng; Ullmann, Ludwig G; Mehta, Jyotigna; Billington, Richard; Woolhiser, Michael R

2008-09-01

The mouse local lymph node assay (LLNA) has become the preferred test for evaluating the dermal sensitization potential of chemicals and requirements are now emerging for its use in the evaluation of their formulated products, especially in the European Union. However, despite its widespread use and extensive validation, the use of this assay for directly testing mixtures and formulated products has been questioned, which could lead to repeat testing using multiple animal models. As pesticide formulations are typically a specific complex blend of chemicals for use as aqueous-based dilutions, traditional vehicles prescribed for the LLNA may change the properties of these formulations leading to inaccurate test results and hazard identification. The objective of this study was to evaluate the effectiveness of an aqueous solution of Pluronic L92 block copolymer surfactant (L92) as a vehicle in the mouse LLNA across five laboratories. Three chemicals with known sensitization potential and four pesticide formulations for which the sensitization potential in guinea pigs and/or humans had previously been assessed were used. Identical LLNA protocols and test materials were used in the evaluation. Assessment of the positive control chemicals, hexylcinnamaldehyde, formaldehyde, and potassium dichromate revealed positive results when using 1% aqueous L92 as the vehicle. Furthermore, results for these chemicals were reproducible among the five laboratories and demonstrated consistent relative potency determinations. The four pesticide formulations diluted in 1% aqueous L92 also demonstrated reproducible results in the LLNA among the five laboratories. Results for these test materials were also consistent with those generated previously using guinea pigs or from human experience. These data support testing aqueous compatible chemicals or pesticide formulations using the mouse LLNA, and provide additional support for the use of 1% aqueous L92 as a suitable, aqueous-based vehicle.

Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

PubMed Central

Salem, Heba F

2010-01-01

The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r2 > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone. PMID:21187946

Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats.

PubMed

Salem, Heba F

2010-11-10

The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r² > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a T(max) of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC₀₋∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles.

PubMed

Ebrahimi, Hossein Ali; Javadzadeh, Yousef; Hamidi, Mehrdad; Jalali, Mohammad Barzegar

2015-09-21

Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations. Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer. The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release. The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.

Use of hydrophobically modified inulin for the preparation of polymethyl methacrylate/polybutyl acrylate latex particles using a semicontinuous reactor.

PubMed

Obiols-Rabasa, M; Ramos, J; Forcada, J; Esquena, J; Solans, C; Levecke, B; Booten, K; Tadros, Tharwat F

2010-06-01

The seeded semicontinuous emulsion copolymerization of methyl methacrylate (MMA) and butyl acrylate (BuA) stabilized with a graft polymeric surfactant based on inulin, INUTEC SP1, as well as its mixture with sodium lauryl sulfate (SLS) is described. The mixture of SLS and Brij58 (alcohol ethoxylated) and the mixture of SLS and Pluronic P85 (block copolymer PEO-PPO-PEO) are also used as surfactant systems. The addition of methacrylic acid (MAA) or acrylic acid (AA) as comonomers is also studied. Previous results proved this inulin-derivative surfactant, INUTEC SP1, to be very effective on synthesizing latexes using a very low surfactant concentration. The kinetic features of the emulsion polymerization (instantaneous conversion and total conversion) were gravimetrically determined along the reactions. Latex dispersions were characterized by photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) to obtain the average particle size, the particle size distributions (PSDs) as well as the polydispersity index (PdI). The stability was determined by turbidimetry measurements and expressed in terms of critical coagulation concentration. The results showed that the use of the graft polymeric surfactant allowed obtaining highly stable nanoparticles, at low surfactant concentrations and high solid contents (up to 37 wt %). This is an improvement with respect to previous works, in which a mixture of the graft polymeric surfactant with another surfactant was required to obtain stable nanoparticles with low polydispersity, at high solid content. In the present work, low polydispersity was achieved using INUTEC as the only emulsifier, which was related to the absence of secondary nucleations. When a mixture of INUTEC SP1 and SLS is used, a wider PSD is obtained due to secondary nucleations. Replacing INUTEC SP1 by other nonionic surfactants such as Brij58 or Pluronic P85 leads to an increase of average particle size and wider PSD.

Co-precipitation of asiatic acid and poly( l-lactide) using rapid expansion of subcritical solutions into liquid solvents

NASA Astrophysics Data System (ADS)

Sane, Amporn; Limtrakul, Jumras

2011-09-01

Poly( l-lactide) (PLLA) nanoparticles loaded with asiatic acid (AA) were successfully produced by rapid expansion of a subcritical solution into an aqueous receiving solution containing a dispersing agent. A mixture of carbon dioxide (CO2) and ethanol (EtOH) with a weight ratio of 1:1 was used as the solvent for AA and PLLA. Two surfactants, Pluronic F127 and sodium dodecyl sulfate were employed. The former was found to be more effective for stabilizing AA-loaded PLLA nanoparticles, as a rapid expansion into a 0.1 wt% Pluronic F127 solution produced a stable nanosuspension consisting mainly of well-dispersed, individual nanoparticles. The effects of rapid expansion-processing conditions—AA to PLLA weight ratio and pre-expansion temperature (Tpre)—on the size and morphology of composite nanoparticles, and the loading capacity and entrapment efficiency of AA in PLLA nanoparticles, were systematically investigated. It was found that AA-loaded PLLA nanoparticles with a size range of 30-100 nm were consistently fabricated by rapid expansion at Tpre of 70-100 °C and AA to PLLA weight ratios of 1:2 and 1:4, and with a constant pre-expansion pressure of 330 bar. The Tpre and AA to PLLA weight ratio had no significant effects on the size of the nanoparticles. The AA to PLLA weight ratio is a controlling parameter for both the loading capacity and the entrapment efficiency of AA in PLLA nanoparticles. The loading capacity and entrapment efficiency increased from 8-11 to 16-21 wt%, and 38-57 to 50-62 wt%, respectively, when the AA to PLLA weight ratio changed from 1:4 to 1:2. However, increasing the Tpre from 70 to 100 °C decreased both the loading capacity and entrapment efficiency of AA in PLLA nanoparticles by 20-30%.

Solubilization of poorly water-soluble drug carbamezapine in pluronic micelles: effect of molecular characteristics, temperature and added salt on the solubilizing capacity.

PubMed

Kadam, Yogesh; Yerramilli, Usha; Bahadur, Anita

2009-08-01

The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle-forming PEO-PPO-PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle-water partition coefficient (P) were determined using UV-vis spectroscopy. Dynamic light scattering on copolymer solutions was used to measure size and polydispersity of nanoaggregates. Solubilization of carbamezapine increased with the rise in temperature and concentration of block copolymers, but no significant increase was observed with added salt (NaCl). The solubilization is also discussed from a thermodynamics viewpoint, by considering the standard free energy of solubilization (DeltaG degrees ).

Research on the Ordered Mesoporous Silica for Tobacco Harm Reduction

NASA Astrophysics Data System (ADS)

Wang, Y.; Y Li, Z.; Ding, J. X.; Hu, Z. J.; Liu, Z.; Zhou, G.; Huang, T. H.

2017-12-01

For reducting tobacco harm, this paper prepared an ordered mesoporous silica by using triblock copolymer Pluronic P123 as template. The property of this material was characterized by the X-ray scattering spectrum(XRD), Transmission electron microscopy(TEM), Scanning electron microscopy (SEM) and Nitrogen adsorption/desorption. Then this ordered mesoporous silica was added into the cigarette filter in order to researching its effect of cigarette harm index. The result shows that the feature of SBA-15 was grain morphology, ordered arrangement, tubular porous 2-D hexagonal structure. The application of SBA-15 in cigarette filter can selectively reduce harmful components in cigarette smoke such as crotonaldehyde, hydrogen cyanide, benzo pyrene and tar. The synthesized SBA-15 could properly reduce cigarette harm index.

Triblock copolymer micelles as templates for preparation of mesoporous niobia thin films

NASA Astrophysics Data System (ADS)

Georgiev, R.; Christova, D.; Todorova, L.; Georgieva, B.; Vasileva, M.; Novakov, Ch; Babeva, T.

2018-03-01

The micelle formation of commercially available Pluronic PE 6800 (PEO-PPO-PEO triblock copolymer) was studied by means of a dye solubilization method, and the solubility of 1,6-diphenyl-1,3,5-hexatriene in aqueous solutions of the copolymer with concentrations ranging from 0.05 to 20 % w/v was studied by recording the transmission and emission spectra of the solutions using UV-VIS and photoluminescence spectroscopy, respectively. Further, mesoporous Nb2O5 films using PE 6800 micelles templates were obtained through sol-gel using spin-coating; their morphology, structure and optical properties were studied by TEM, SAED and nonlinear fitting of reflectance measurements. The possible application of the films in optical sensing of vapors was demonstrated and discussed.

Catalytic performance of subtilisin immobilized without covalently attachment on surface-functionalized mesoporous silica materials

NASA Astrophysics Data System (ADS)

Murai, K.; Nonoyama, T.; Ando, F.; Kato, K.

2011-10-01

Mesoporous silica (MPS) materials were synthesized using cetyltrimethylammonium bromide or amphiphilic pluronic polymer P123 (EO20PO70EO20) as structure-directing agent. MPS samples were characterized by FE-SEM and N2 adsorption-desorption isotherms, respectively. Subtilisin from Bacillus licheiformis (4.1 × 7.8 × 3.7 nm) was easily immobilized by a direct one-step immobilization process onto MPS with different organo-functinalized surfaces. However, enzyme immobilized on MPS modified with 3-mercaptopropyl group strongly reduced its enantioselectivity. Denaturation temperature of immobilized subtilisin shifted to a high temperature compared to free-enzyme. These biocatalysts on MPS particles retained about 30% of original activity even after 5 cycles of recycle use.

Chlorhexidine hexametaphosphate as a wound care material coating: antimicrobial efficacy, toxicity and effect on healing.

PubMed

Barbour, Michele E; Maddocks, Sarah E; Grady, Helena J; Roper, James A; Bass, Mark D; Collins, Andrew M; Dommett, Rachel M; Saunders, Margaret

2016-08-01

In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials. CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure. Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials. CHX-HMP coated materials had less toxic effect on human placental cells than commercial chlorhexidine dressings. CHX-HMP in pluronic gel did not delay healing but reduced wound colonization by E. faecalis. CHX-HMP could become a useful component of wound care materials with sustained antimicrobial efficacy, lower toxicity than chlorhexidine digluconate materials, and reduction in wound colonization without affecting closure.

Photodynamic therapy and two-photon bio-imaging applications of hydrophobic chromophores through amphiphilic polymer delivery.

PubMed

Gallavardin, Thibault; Maurin, Mathieu; Marotte, Sophie; Simon, Timea; Gabudean, Ana-Maria; Bretonnière, Yann; Lindgren, Mikael; Lerouge, Frédéric; Baldeck, Patrick L; Stéphan, Olivier; Leverrier, Yann; Marvel, Jacqueline; Parola, Stéphane; Maury, Olivier; Andraud, Chantal

2011-07-01

The synthesis and photophysical properties of two lipophilic quadrupolar chromophores featuring anthracenyl (1) or dibromobenzene (2) were described. These two chromophores combined significant two-photon absorption cross-sections with high fluorescence quantum yield for 1 and improved singlet oxygen generation efficiency for 2, in organic solvents. The use of Pluronic nanoparticles allowed a simple and straightforward introduction of these lipophilic chromophores into biological cell media. Their internal distribution in various cell lines was studied using fluorescence microscopy and flow-cytometry following a successful staining that was achieved upon 2 h of incubation. Finally, multiphoton excitation microscopy and photodynamic therapy capability of the chromophores were demonstrated by cell exposure to a 820 nm fs laser and cell death upon one photon resonant irradiation at 436 ± 10 nm, respectively.

Template-assisted electrostatic spray deposition as a new route to mesoporous, macroporous, and hierarchically porous oxide films.

PubMed

Sokolov, S; Paul, B; Ortel, E; Fischer, A; Kraehnert, R

2011-03-01

A novel film coating technique, template-assisted electrostatic spray deposition (TAESD), was developed for the synthesis of porous metal oxide films and tested on TiO(2). Organic templates are codeposited with the titania precursor by electrostatic spray deposition and then removed during calcination. Resultant films are highly porous with pores casted by uniformly sized templates, which introduced a new level of control over the pore morphology for the ESD method. Employing the amphiphilic block copolymer Pluronic P123, PMMA latex spheres, or a combination of the two, mesoporous, macroporous, and hierarchically porous TiO(2) films are obtained. Decoupled from other coating parameters, film thickness can be controlled by deposition time or depositing multiple layers while maintaining the coating's structure and integrity.

A newly developed silymarin nanoformulation as a potential antidiabetic agent in experimental diabetes.

PubMed

El-Far, Yousra M; Zakaria, Mahmoud M; Gabr, Mahmoud M; El Gayar, Amal M; El-Sherbiny, Ibrahim M; Eissa, Laila A

2016-10-01

This study aimed to develop a new stable nanoformulation of silymarin (SM) with optimum enhanced oral bioavailability and to evaluate its effect as well as mechanism of action as a superior antidiabetic agent over native SM using streptozotocin-induced diabetic rats. SM-loaded pluronic nanomicelles (SMnp) were prepared and fully characterized. Biochemical parameters were performed as well as histological, confocal and reverse-transcription polymerase chain reaction studies on pancreatic target tissues. SMnp were found to improve significantly the antihyperglycemic, antioxidant and antihyperlipidemic properties as compared with native SM. In addition, SMnp was found to be a more efficient agent over SM in the management of diabetes and its associated complications due to its superior bioavailability in vivo, and the controlled release profile of SM. [Formula: see text].

Flexible, cathodoluminescent and free standing mesoporous silica films with entrapped quasi-2D perovskites

NASA Astrophysics Data System (ADS)

Vassilakopoulou, Anastasia; Papadatos, Dionysios; Koutselas, Ioannis

2017-04-01

The effective entrapment of hybrid organic-inorganic semiconductors (HOIS) into mesoporous polymer-silica hybrid matrices, formed as free standing flexible films, is presented for the first time. A blend of quasi-2D HOIS, simply synthesized by mixing two-dimensional (2D) and three dimensional (3D) HOIS, exhibiting strong photoluminescence, is embedded into porous silica matrices during the sol-gel synthesis, using tetraethylorthosilicate as precursor and Pluronic F-127 triblock copolymer as structure directing agent, under acidic conditions. The final nanostructure hybrid forms flexible, free standing films, presenting high cathodoluminescence and long stable excitonic luminescence, indicating the protective character of the hybrid matrix towards the entrapped perovskite. A significant result is that the photoluminescence of the entrapped HOIS is not affected even after films' prolonged exposure to water.

Direct synthesis and application of bridged diamino-functionalized periodic mesoporous organosilicas with high nitrogen contents

NASA Astrophysics Data System (ADS)

Zhu, Feng-Xia; Zhao, Pu-Su; Sun, Xiao-Jun; An, Li-Tao; Deng, Yong; Wu, Jia-Min

2017-11-01

Bridged diamino-functionalized periodic mesoporous organosilicas [BD-PMO(Et), Et = ethyl] materials were synthesized directly by co-condensation of 2-bis (triethoxysilyl)ethane (BTEE) and 1,4-bis[3-(tirmethoxysilyl)-propyl]ethylenediamino (BTMSEN) under acidic conditions with pluronic triblock copolymer P123 as a template. The nitrogen content in BD-PMO(Et) could be adjusted up to 40% without disturbing the ordered mesoporous structure. These materials were proved to be effective heterogeneous catalysts for the liquid-phase reactions such as Knoevenagel and Henry condensations as well as in the intermolecular cross-double-Michael addition reaction between α-methyl-β-nitrostyrene and α, β-unsaturated ketone. They exhibited comparable catalytic activities with homogeneous catalyst piperazine and can be reused for several times without any negative environmental impact.

Design and synthesis of magnetic nanoparticles with gold shells for single particle optical tracking

NASA Astrophysics Data System (ADS)

Lim, Jitkang

The design, synthesis, and characterization of iron oxide core, gold shell nanoparticles are studied in this thesis. Firstly, nanoparticles with 18 +/- 1.7 nm diameter iron oxide cores with ˜5 nm thick gold shells were synthesized via a new seed-mediated electroless deposition method. The nanoparticles were superparamagnetic at room temperature and could be reversibly collected by a permanent magnet. These nanoparticles displayed a sharp localized surface plasmon resonance peak at 605 nm, as predicted by scattering theory, and their large scattering cross-section allowed them to be individually resolved in darkfield optical microscopy while undergoing Brownian motion in aqueous suspension. Later, commercially available 38 +/- 3.8 nm diameter spherical iron oxide nanoparticles (from Ocean Nanotech, Inc) were employed to make core-shell particles. These particles were decorated with cationic poly(diallyldimethylammonium chloride) (PDDA) which further promotes the attachment of small gold clusters. After gold seeding, the average hydrodynamic diameter of the core-shell particles is 172 +/- 65.9 nm. The magnetophoretic motion of these particles was guided by a piece of magnetized mu-metal. Individual particle trajectories were observed by darkfield optical microscopy. The typical magnetophoretic velocity achieved was within the range of 1--10 mum/sec. Random walk analysis performed on these particles while undergoing Brownian motion confirmed that individual particles were indeed being imaged. The particle size variation within the observed sample obtained through random walk analysis was within the size distribution obtained by dynamic light scattering. When the current to the solenoid used to magnetize the mu-metal was turned off, all the collected core-shell particles were readily redispersed by diffusion back into the surrounding environment. A Peclet number analysis was performed to probe the convective motion of nanospheres and nanorods under the influence of magnetophoresis and diffusion. Under most circumstances, magnetophoretic behavior dominates diffusion for nanorods, as the magnetic field lines tend to align the magnetic moment along the rod axis. The synthesis and dispersion of fluorophore-tagged nanorods are described. Fluorescence microscopy was employed to image the nanorod motion in a magnetic field gradient. The preliminary experimental data are consistent with the Peclet number analysis. Lastly, the colloidal stability of iron oxide core, gold shell nanoparticles in high ionic strength media was investigated. Such particles are sufficiently charged to be stable against flocculation without modification in low ionic strength media, but they require surface modification to be stably dispersed in elevated ionic strength media that are appropriate for biotechnological applications. Dynamic light scattering and ultraviolet-visible spectrophotometry were used to monitor the colloidal stability of core-shell particles in pH 7.4, 150 mM ionic strength phosphate buffered saline (PBS). While uncoated particles flocculated immediately upon being introduced into PBS, core-shell particles with adsorbed layers of bovine serum albumin or the amphiphilic triblock copolymers Pluronic F127 and Pluronic F68 resist flocculation after more than five days in PBS. Adsorbed dextran allowed flocculation that was limited to the formation of small clusters, while poly(ethylene glycol) homopolymers ranging in molecular weight from 6,000 to 100,000 were ineffective steric stabilizers. The effectiveness of adsorbed Pluronic copolymers as steric stabilizers was interpreted in terms of the measured adsorbed layer thickness and extended DLVO theory predictions of the interparticle interactions.

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells.

PubMed

Punfa, Wanisa; Yodkeeree, Supachai; Pitchakarn, Pornsiri; Ampasavate, Chadarat; Limtrakul, Pornngarm

2012-06-01

To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 μg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 μg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.

CO2-switchable fluorescence of a dendritic polymer and its applications

NASA Astrophysics Data System (ADS)

Gao, Chunmei; Lü, Shaoyu; Liu, Mingzhu; Wu, Can; Xiong, Yun

2015-12-01

The synthesis and properties of CO2 responsive and fluorescent dendritic polymers, poly(amido amine)/Pluronic F127 (PAMAM/F127), are reported in this paper. The morphologies and sizes of PAMAM/F127 dendritic polymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). PAMAM/F127 dendritic polymers showed unimolecular micelle morphologies at low concentrations, and changed to multimolecular micelles at higher concentrations. Additionally, fluorescence spectra and confocal laser scanning microscopy images showed that PAMAM/F127 dendritic polymers exhibited a fluorescent enhancement response to the presence of CO2. Apart from that, the release behavior of PAMAM/F127 gels under simulated body fluids was investigated by choosing curcumin as the hydrophobic drug. The results indicated that PAMAM/F127 dendritic polymers can be used to improve the solubility of curcumin, and the drug released faster in the presence of CO2. Such CO2 responsive fluorescent dendritic polymers are potentially applicable in cellular imaging or drug controlled release.The synthesis and properties of CO2 responsive and fluorescent dendritic polymers, poly(amido amine)/Pluronic F127 (PAMAM/F127), are reported in this paper. The morphologies and sizes of PAMAM/F127 dendritic polymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). PAMAM/F127 dendritic polymers showed unimolecular micelle morphologies at low concentrations, and changed to multimolecular micelles at higher concentrations. Additionally, fluorescence spectra and confocal laser scanning microscopy images showed that PAMAM/F127 dendritic polymers exhibited a fluorescent enhancement response to the presence of CO2. Apart from that, the release behavior of PAMAM/F127 gels under simulated body fluids was investigated by choosing curcumin as the hydrophobic drug. The results indicated that PAMAM/F127 dendritic polymers can be used to improve the solubility of curcumin, and the drug released faster in the presence of CO2. Such CO2 responsive fluorescent dendritic polymers are potentially applicable in cellular imaging or drug controlled release. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06729d

Quantitative atomic-scale structure characterization of ordered mesoporous carbon materials by solid state NMR

DOE PAGES

Wang, Zhuoran; Opembe, Naftali; Kobayashi, Takeshi; ...

2018-02-03

In this study, solid-state (SS)NMR techniques were applied to characterize the atomic-scale structures of ordered mesoporous carbon (OMC) materials prepared using Pluronic F127 as template with resorcinol and formaldehyde as polymerizing precursors. A rigorous quantitative analysis was developed using a combination of 13C SSNMR spectra acquired with direct polarization and cross polarization on natural abundant and selectively 13C-enriched series of samples pyrolyzed at various temperatures. These experiments identified and counted the key functional groups present in the OMCs at various stages of preparation and thermal treatment. Lastly, the chemical evolution of molecular networks, the average sizes of aromatic clusters andmore » the extended molecular structures of OMCs were then inferred by coupling this information with the elemental analysis results.« less

Quantitative atomic-scale structure characterization of ordered mesoporous carbon materials by solid state NMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhuoran; Opembe, Naftali; Kobayashi, Takeshi

In this study, solid-state (SS)NMR techniques were applied to characterize the atomic-scale structures of ordered mesoporous carbon (OMC) materials prepared using Pluronic F127 as template with resorcinol and formaldehyde as polymerizing precursors. A rigorous quantitative analysis was developed using a combination of 13C SSNMR spectra acquired with direct polarization and cross polarization on natural abundant and selectively 13C-enriched series of samples pyrolyzed at various temperatures. These experiments identified and counted the key functional groups present in the OMCs at various stages of preparation and thermal treatment. Lastly, the chemical evolution of molecular networks, the average sizes of aromatic clusters andmore » the extended molecular structures of OMCs were then inferred by coupling this information with the elemental analysis results.« less

Size-Tunable and Functional Core-Shell Structured Silica Nanoparticles for Drug Release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Fangli; Guo, Ya Nan; Liu, Jun

2010-02-18

Size-tunable silica cross-linked micellar core-shell nanoparticles (SCMCSNs) were successfully synthesized from a Pluronic nonionic surfactant (F127) template system with organic swelling agents such as 1,3,5-trimethylbenzene (TMB) and octanoic acid at room temperature. The size and morphology of SCMCSNs were directly evidenced by TEM imaging and DLS measurements (up to ~90 nm). Pyrene and coumarin 153 (C153) were used as fluorescent probe molecules to investigate the effect and location of swelling agent molecules. Papaverine as a model drug was used to measure the loading capacity and release property of nanoparticles. The swelling agents can enlarge the nanoparticle size and improve themore » drug loading capacity of nanoparticles. Moreover, the carboxylic acid group of fatty acid can adjust the release behavior of the nanoparticles.« less

Preparation and physicochemical of microemulsion based on macadamia nut oil

NASA Astrophysics Data System (ADS)

Tu, Xinghao; Chen, Hong; Du, Liqing

2018-03-01

The objective of the present work was to study the preparation, optimization and characteristic of nanostructured lipid carriers(NLCs) based on macadamia nut oil. NLC with various macadamia nut oil content were successfully prepared by an optimized microfluidization method using stearic acid as solid lipid and pluronic F68 as surfactant. As a result, NLC with particle size about 286nm were obtained, and the polydispersity index(PI) of all developed NLC were below 0.2 which indicate a narrow size distribution. Furthermore, the encapsulation efficiency and loading capability were investigated as well. Physical stability of NLC demonstrated that particles of system were stable at room temperature and low temperature. Differential scanning calorimetry(DSC) investigation show that the inner structure and recrystallinity of lipid matrix within NLC were greatly influenced by the content of macadamia nut oil.

Selective functionalization of the mesopores of SBA-15

DOE PAGES

Webb, Jonathan D.; Seki, Tomohiro; Goldston, Jennifer F.; ...

2014-10-23

In this study, a method has been developed that permits the highly selective functionalization of the interior and exterior surfaces of the ubiquitous mesoporous material, SBA-15. The key step is reloading the as-synthesized material with structure-directing agent, Pluronic ® P123, prior to selective functionalization of the external surface with a silylating agent. This new approach represents a significant improvement over literature procedures. Results from physisorption analyses as well as solid-state NMR permit a detailed, quantitative assessment of functionalized SBA-15. This work also provides insight into the stability of the silyl layer during extraction procedures – an issue often neglected inmore » other studies but of significant importance as decomposition of this layer could result in the introduction of new silanols and reduce the effectiveness of any selective grafting procedure.« less

PEO-PPO-PEO Tri-Block Copolymers for Gene Delivery Applications in Human Regenerative Medicine—An Overview

PubMed Central

Cucchiarini, Magali

2018-01-01

Lineal (poloxamers or Pluronic®) or X-shaped (poloxamines or Tetronic®) amphiphilic tri-block copolymers of poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO-PEO) have been broadly explored for controlled drug delivery in different regenerative medicine approaches. The ability of these copolymers to self-assemble as micelles and to undergo sol-to-gel transitions upon heating has endowed the denomination of “smart” or “intelligent” systems. The use of PEO-PPO-PEO copolymers as gene delivery systems is a powerful emerging strategy to improve the performance of classical gene transfer vectors. This review summarizes the state of art of the application of PEO-PPO-PEO copolymers in both nonviral and viral gene transfer approaches and their potential as gene delivery systems in different regenerative medicine approaches. PMID:29518011

The effects of non-ionic polymeric surfactants on the cleaning of biofouled hydrogel materials.

PubMed

Guan, Allan; Li, Zhenyu; Phillips, K Scott

2015-01-01

Block co-polymer surfactants have been used for cleaning hydrogel medical devices that contact the body (e.g., contact lenses) because of their biocompatibility. This work examined the relationship between concentration and detergency of two non-ionic polymeric surfactants (Pluronic F127 and Triton X-100) for cleaning protein soil, with anionic surfactants (sodium dodecyl sulfate and sodium laureth sulfate) as positive controls. Surface plasmon resonance was used to quantify removal of simulated tear soil from self-assembled monolayer surfaces, and a microplate format was used to study the removal of fluorescently labeled soil proteins from contact lenses. While detergency increased as a function of concentration for anionic surfactants, it decreased with concentration for the two polymeric surfactants. The fact that the protein detergency of some non-ionic polymeric surfactants did not increase with concentration above the critical micelle concentration could have implications for optimizing the tradeoff between detergency and biocompatibility.

Nanoformulated water-soluble paclitaxel to enhance drug efficacy and reduce hemolysis side effect.

PubMed

Gu, Weiting; Chen, Jie; Patra, Prabir; Yang, Xiaoyan; Gu, Quanrong; Wei, Lingxuan; Acker, Jason P; Kong, Beihua

2017-07-01

Surgery, chemotherapy, and radiotherapy are the three top cancer treatment modalities. Paclitaxel (PTX) is one of the most widely used chemotherapy drugs. However, its clinical applications have been significantly limited due to: (i) serious hemolysis effect of currently available commercial paclitaxel formulations and (ii) its water insolubility. An easy way to deliver paclitaxel by a new nanocarrier system using pluronic copolymers of P123/F68 and Sorbitan monopalmitate (Span 40) was reported in our previous research article. The characterization of the formulation and analysis of drug release and cellular uptake were also presented. In this article, we reported discoveries of our follow-up in vivo antitumor and in vitro hemolytic study discoveries. The experimental results showed that the nanoformulated PTX achieved much better tumor suppression performance while reducing hemolysis side effects. This newly formulated drug can significantly improve patient outcomes in cancer chemotherapy.

Foam generation and sample composition optimization for the FOAM-C experiment of the ISS

NASA Astrophysics Data System (ADS)

Carpy, R.; Picker, G.; Amann, B.; Ranebo, H.; Vincent-Bonnieu, S.; Minster, O.; Winter, J.; Dettmann, J.; Castiglione, L.; Höhler, R.; Langevin, D.

2011-12-01

End of 2009 and early 2010 a sealed cell, for foam generation and observation, has been designed and manufactured at Astrium Friedrichshafen facilities. With the use of this cell, different sample compositions of "wet foams" have been optimized for mixtures of chemicals such as water, dodecanol, pluronic, aethoxisclerol, glycerol, CTAB, SDS, as well as glass beads. This development is performed in the frame of the breadboarding development activities of the Experiment Container FOAM-C for operation in the ISS Fluid Science Laboratory (ISS). The sample cell supports multiple observation methods such as: Diffusing-Wave and Diffuse Transmission Spectrometry, Time Resolved Correlation Spectroscopy [1] and microscope observation, all of these methods are applied in the cell with a relatively small experiment volume <3cm3. These units, will be on orbit replaceable sets, that will allow multiple sample compositions processing (in the range of >40).

Monodisperse Carbon Nanospheres with Hierarchical Porous Structure as Electrode Material for Supercapacitor

NASA Astrophysics Data System (ADS)

Yang, Xiutao; Xia, Hui; Liang, Zhongguan; Li, Haiyan; Yu, Hongwen

2017-09-01

Carbon nanospheres with distinguishable microstructure were prepared by carbonization and subsequent KOH activation of F108/resorcinol-formaldehyde composites. The dosage of triblock copolymer Pluronic F108 is crucial to the microstructure differences. With the adding of F108, the polydisperse carbon nanospheres (PCNS) with microporous structure, monodisperse carbon nanospheres (MCNS) with hierarchical porous structure, and agglomerated carbon nanospheres (ACNS) were obtained. Their microstructure and capacitance properties were carefully compared. As a result of the synergetic effect of mono-dispersion spheres and hierarchical porous structures, the MCNS sample shows improved electrochemical performance, i.e., the highest specific capacitance of 224 F g-1 (0.2 A g-1), the best rate capability (73% retention at 20 A g-1), and the most excellent capacitance retention of 93% over 10,000 cycles, making it to be the promising electrode material for high-performance supercapacitors.

Versatile magnetometer assembly for characterizing magnetic properties of nanoparticles.

PubMed

Araujo, J F D F; Bruno, A C; Louro, S R W

2015-10-01

We constructed a versatile magnetometer assembly for characterizing iron oxide nanoparticles. The magnetometer can be operated at room temperature or inside a cryocooler at temperatures as low as 6 K. The magnetometer's sensor can be easily exchanged and different detection electronics can be used. We tested the assembly with a non-cryogenic commercial Hall sensor and a benchtop multimeter in a four-wire resistance measurement scheme. A magnetic moment sensitivity of 8.5 × 10(-8) Am(2) was obtained with this configuration. To illustrate the capability of the assembly, we synthesized iron oxide nanoparticles coated with different amounts of a triblock copolymer, Pluronic F-127, and characterized their magnetic properties. We determined that the polymer coating does not affect the magnetization of the particles at room temperature and demonstrates that it is possible to estimate the average size of coating layers from measurements of the magnetic field of the sample.

Versatile magnetometer assembly for characterizing magnetic properties of nanoparticles

NASA Astrophysics Data System (ADS)

Araujo, J. F. D. F.; Bruno, A. C.; Louro, S. R. W.

2015-10-01

We constructed a versatile magnetometer assembly for characterizing iron oxide nanoparticles. The magnetometer can be operated at room temperature or inside a cryocooler at temperatures as low as 6 K. The magnetometer's sensor can be easily exchanged and different detection electronics can be used. We tested the assembly with a non-cryogenic commercial Hall sensor and a benchtop multimeter in a four-wire resistance measurement scheme. A magnetic moment sensitivity of 8.5 × 10-8 Am2 was obtained with this configuration. To illustrate the capability of the assembly, we synthesized iron oxide nanoparticles coated with different amounts of a triblock copolymer, Pluronic F-127, and characterized their magnetic properties. We determined that the polymer coating does not affect the magnetization of the particles at room temperature and demonstrates that it is possible to estimate the average size of coating layers from measurements of the magnetic field of the sample.

Effect of nucleoside analogue antimetabolites on the structure of PEO–PPO–PEO micelles investigated by SANS

DOE PAGES

Han, Youngkyu; Zhang, Zhe; Smith, Gregory S.; ...

2017-04-19

In this work, the effect of three nucleoside analogue antimetabolites (5-fluorouracil, floxuridine, and gemcitabine) on the structure of Pluronic L62 copolymer micelles was investigated using small-angle neutron scattering. These antimetabolites used for cancer chemotherapy have analogous molecular structures but different molecular sizes and aqueous solubilities. It was found that the addition of the three antimetabolites slightly reduced the micellar size and aggregation number, and the micellar anisotropy. The added antimetabolites also changed the internal molecular distribution of the micelles as measured by the scattering length densities, resulting in enhanced hydration of the hydrophobic core region of the micelle. The strengthmore » of the effect was found to correlate with the molecular properties of the model drugs, i.e. a larger molecular size and a higher aqueous solubility lead to enhanced hydration of the micellar core.« less

Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications

DOE PAGES

Wu, Xiang; Zhang, Yuanwei; Takle, Kendra; ...

2016-01-06

A near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. We achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb 3+ ) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We also demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogeneticmore » neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.« less

Mesoporous silicas synthesis and application for lignin peroxidase immobilization by covalent binding method.

PubMed

Hu, Zunfang; Xu, Longqian; Wen, Xianghua

2013-01-01

Immobilization of enzymes on mesoporous silicas (MS) allows for good reusability. MS with two-dimensional hexagonal pores in diameter up to 14.13 nm were synthesized using Pluronic P123 as template and 1,3,5-triisopropylbenzene as a swelling agent in acetate buffer. The surface of MS was modified by the silanization reagents 3-aminopropyltriethoxysilane. Lignin peroxidase (LiP) was successfully immobilized on the modified MS through covalent binding method by four agents: glutaraldehyde, 1,4-phenylene diisothiocyanate, cyanotic chloride and water-soluble carbodiimide. Results showed that cyanotic chloride provided the best performance for LIP immobilization. The loaded protein concentration was 12.15 mg/g and the immobilized LiP activity was 812.9 U/L. Immobilized LiP had better pH stability. Acid Orange II was used to examine the reusability of immobilized LiP, showing more than 50% of the dye was decolorized at the fifth cycle.

Cultivation and energy efficient harvesting of microalgae using thermoreversible sol-gel transition

PubMed Central

Estime, Bendy; Ren, Dacheng; Sureshkumar, Radhakrishna

2017-01-01

Microalgae represent a promising source of renewable biomass for the production of biofuels and valuable chemicals. However, energy efficient cultivation and harvesting technologies are necessary to improve economic viability. A Tris-Acetate-Phosphate-Pluronic (TAPP) medium that undergoes a thermoreversible sol-gel transition is developed to efficiently culture and harvest microalgae without affecting the productivity as compared to that in traditional culture in a well-mixed suspension. After seeding microalgae in the TAPP medium in a solution phase at 15 °C, the temperature is increased by 7 °C to induce gelation. Within the gel, microalgae are observed to grow in large clusters rather than as isolated cells. The settling velocity of the microalgal clusters is approximately ten times larger than that of individual cells cultured in typical solution media. Such clusters are easily harvested gravimetrically by decreasing the temperature to bring the medium to a solution phase. PMID:28102313

Aggregation behaviors of PEO-PPO-ph-PPO-PEO and PPO-PEO-ph-PEO-PPO at an air/water interface: experimental study and molecular dynamics simulation.

PubMed

Gong, Houjian; Xu, Guiying; Liu, Teng; Xu, Long; Zhai, Xueru; Zhang, Jian; Lv, Xin

2012-09-25

The block polyethers PEO-PPO-ph-PPO-PEO (BPE) and PPO-PEO-ph-PEO-PPO (BEP) are synthesized by anionic polymerization using bisphenol A as initiator. Compared with Pluronic P123, the aggregation behaviors of BPE and BEP at an air/water interface are investigated by the surface tension and dilational viscoelasticity. The molecular construction can influence the efficiency and effectiveness of block polyethers in decreasing surface tension. BPE has the most efficient ability to decrease surface tension of water among the three block polyethers. The maximum surface excess concentration (Γ(max)) of BPE is larger than that of BEP or P123. Moreover, the dilational modulus of BPE is almost the same as that of P123, but much larger than that of BEP. The molecular dynamics simulation provides the conformational variations of block polyethers at the air/water interface.

Effects of polyalkylene glycols and fatty acid soaps on properties of synthetic lubricating-cooling fluids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stulii, A.A.

1983-01-01

The lack of any effect of the polyalkylene glycols on the series of properties of the fatty acid soaps was confirmed by replacing the PEG-35 in the synthetic lubricating-cooling fluid (LCF) by a polyethylene glycol with a molecular weight of 400 or 6000, a propylene oxide oligomer with a molecular weight of 700, or a copolymer of ethylene and propylene oxides (Pluronic 44, Pluriol PE-6400, Hydropol 200). Attempts to select surfactants and optimal concentrations in synthetic LCFs based on polyalkylene glycols. Indicates that of the studied soaps, those of the most interest are the triethanolamine soaps of individual C/sub 6/-C/submore » 10/ fatty acids and commercial mixed C/sub 7/-C/sub 9/ synthetic fatty acids. Finds that the polyalkylene glycols and the indicated soaps supplement each other, imparting the required set of properties to the LCF.« less

Therapeutic surfactant-stripped frozen micelles

NASA Astrophysics Data System (ADS)

Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

2016-05-01

Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

Effect of nucleoside analogue antimetabolites on the structure of PEO–PPO–PEO micelles investigated by SANS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Youngkyu; Zhang, Zhe; Smith, Gregory S.

2017-01-01

The effect of three nucleoside analogue antimetabolites (5-fluorouracil, floxuridine, and gemcitabine) on the structure of Pluronic L62 copolymer micelles was investigated using small-angle neutron scattering. These antimetabolites used for cancer chemotherapy have analogous molecular structures but different molecular sizes and aqueous solubilities. It was found that the addition of the three antimetabolites slightly reduced the micellar size and aggregation number, and the micellar anisotropy. The added antimetabolites also changed the internal molecular distribution of the micelles as measured by the scattering length densities, resulting in enhanced hydration of the hydrophobic core region of the micelle. The strength of the effectmore » was found to correlate with the molecular properties of the model drugs, i.e. a larger molecular size and a higher aqueous solubility lead to enhanced hydration of the micellar core.« less

Effect of acid on the aggregation of poly(ethylene xide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers.

PubMed

Yang, Bin; Guo, Chen; Chen, Shu; Ma, Junhe; Wang, Jing; Liang, Xiangfeng; Zheng, Lily; Liu, Huizhou

2006-11-23

The acid effect on the aggregation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers EO(20)PO(70)EO(20) has been investigated by transmission electron microscopy (TEM), particle size analyzer (PSA), Fourier transformed infrared, and fluorescence spectroscopy. The critical micellization temperature for Pluronic P123 in different HCl aqueous solutions increases with the increase of acid concentration. Additionally, the hydrolysis degradation of PEO blocks is observed in strong acid concentrations at higher temperatures. When the acid concentration is low, TEM and PSA show the increase of the micelle mean diameter and the decrease of the micelle polydispersity at room temperature, which demonstrate the extension of EO corona and tendency of uniform micelle size because of the charge repulsion. When under strong acid conditions, the aggregation of micelles through the protonated water bridges was observed.

Doxorubicin loaded magneto-niosomes for targeted drug delivery.

PubMed

Tavano, Lorena; Vivacqua, Marco; Carito, Valentina; Muzzalupo, Rita; Caroleo, Maria Cristina; Nicoletta, Fiore

2013-02-01

In chemotherapy the magnetic drug targeting to a specific organ or tissue is proposed on the assumption that magnetic fields are harmless to biological systems. In this light we have vehiculated doxorubicin as model drug by novel magneto-niosomes in order to evaluate the physico-chemical properties of the obtained formulations and the in vitro release profile. Tween 60 and Pluronic L64 have been used as surfactants and the formulation cytotoxicity has been performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide and trypan blue dye esclusion tests. Results show that niosome dimensions and doxorubicin entrapment efficiencies are influenced by bilayer composition. In addition, formulations are able to control the deliver and release of the drug active form in a retarded manner. No additional toxicity, due to the encapsulation of ferrofluid into niosomes core, has been detected. Copyright © 2012 Elsevier B.V. All rights reserved.

Facile fabrication of high-quality Ag/PS coaxial nanocables based on the mixed mode of soft/hard templates

NASA Astrophysics Data System (ADS)

Wan, Mimi; Zhao, Wenbo; Peng, Fang; Wang, Qi; Xu, Ping; Mao, Chun; Shen, Jian

2016-08-01

A new kind of high-quality Ag/PS coaxial nanocables can be facilely synthesized by using soft/hard templates method. In order to effectively introduce Ag sources into porous polystyrene (PS) nanotubes which were trapped in porous anodic aluminum oxide (AAO) hard template, Pluronic F127 (F127) was used as guiding agent, soft template and reductant. Meanwhile, ethylene glycol solution was also used as solvent and co-reducing agent to assist in the formation of silver nanowires. The influences of concentration of F127 and reducing reaction time on the formation of Ag/PS coaxial nanocables were discussed. Results indicated that the high-quality Ag/PS coaxial nanocables can be obtained by the mixed mode of soft/hard templates under optimized conditions. This strategy is expected to be extended to design more metal/polymer coaxial nanocables for the benefit of creation of complex and functional nanoarchitectures and components.

Multifunctional activities of KSLW synthetic antimicrobial decapeptide: Implications for wound healing

NASA Astrophysics Data System (ADS)

Williams, Richard Leroy

Wound healing is a complex process leading to the maintenance of skin integrity. Stress is known to increase susceptibility to bacterial infection, alter proinflammatory cytokine expression, and delay wound closure. Recently, antimicrobial peptides have generated interest due to their prokaryotic selectivity, decreased microbial resistance and multifunctional roles in wound healing, including fibroblast stimulation, keratinocyte migration and leukocyte migration. The objective of this dissertation project was to evaluate the effect of a synthetic antimicrobial decapeptide (KSLW) on bacterial clearance inflammation, and wound closure during stress-impaired healing. SKH-1 mice were randomly assigned to either control or restraint-stressed (RST) groups. Punch biopsy wounds (3.5 mm in diameter) were created bilaterally on the dorsal skin. Wounds were injected with 50 microL of empty carriers or KSLW prepared in Pluronic-F68, phospholipid micelles, or saline. Bacterial assays of harvested wounds were conducted on BHI agar. Wound closure was determined by photoplanimetry. Cytokine and growth factor mRNA expression was assessed with real-time RT-PCR. Human neutrophil migration assays and checkerboard analyses were performed using Transweli plates, and counting on hemacytometer. Oxidative burst activity was measured by spectrophotometric analysis of 2,7-dichlorofluorescein oxidation. KSLW-treatment resulted in significant reductions in bacterial load among RST mice, with no difference from control after 24h. The effect was sustained 5 days post-wounding, in RST mice treated with KSLW-F68. Temporal analysis of gene induction revealed reversals of stress-induced altered expression of growth factors, proinflammatory cytokines, and chemokines essential for favorable wound healing, at various time points. KSLW-treatment in RST mice demonstrated faster wound closure throughout the stress period. KSLW, at micromolar concentrations, demonstrated a significant effect on neutrophil migration and oxidative burst. These data suggest KSLW enhances bacterial clearance and promotes proinflammatory activity during early wound healing in stressed mice. Peptide delivery in Pluronic-F68 demonstrated increased substantivity, with faster wound closure, compared to other delivery systems. In addition to its antimicrobial activity, KSLW was shown to enhance neutrophil chemotaxis and sustain cell viability by inhibition of oxidative burst responses. Taken together, the cationic peptide may be implicated in the management of infection in different systems demonstrating impaired healing, including diabetes, age, hormone-imbalance, and bum models.

Immunization of Mice by BCG Formulated HCV Core Protein Elicited Higher Th1-Oriented Responses Compared to Pluronic-F127 Copolymer

PubMed Central

Yazdanian, Maryam; Memarnejadian, Arash; Mahdavi, Mehdi; Sadat, Seyed Mehdi; Motevali, Fatemeh; Vahabpour, Rouhollah; Khanahmad, Hossein; Siadat, Seyed Davar; Aghasadeghi, Mohammad Reza; Roohvand, Farzin

2013-01-01

Background A supreme vaccine for Hepatitis C virus (HCV) infection should elicit strong Th1-oriented cellular responses. In the absence of a Th1-specific adjuvant, immunizations by protein antigens generally induce Th2-type and weak cellular responses. Objectives To evaluate the adjuvant effect of BCG in comparison with nonionic copolymer-Pluronic F127 (F127) as a classic adjuvant in the formulation of HCV core protein (HCVcp) as a candidate vaccine for induction of Th1 immune responses. Materials and Methods Expression of N-terminally His-Tagged HCVcp (1-122) by pIVEX2.4a-core vector harboring the corresponding gene under the control of arabinose-inducible (araBAD) promoter was achieved in BL21-AI strain of E.coli and purified through application of nitrilotriacetic acid (Ni-NTA) chromatography. Mice were immunized subcutaneously (s.c.) in base of the tail with 100 μl of immunogen (F127+HCVcp or BCG+HCVcp; 5 μgHCVcp/mouse/dose) or control formulations (PBS, BCG, F127) at weeks 0, 3, 6. Total and subtypes of IgG, as well as cellular immune responses (Proliferation, In vivo CTL and IFN-γ/IL-4 ELISpot assays against a strong and dominant H2-d restricted, CD8+-epitopic peptide, core 39-48; RRGPRLGVRA of HCVcp) were compared in each group of immunized animals. Results Expression and purification of core protein around the expected size (21 kDa) was confirmed by Western blotting. The HCVcp + BCG vaccinated mice showed significantly higher lymphocyte proliferation and IFN-γ production but lower levels of cell lysis (45% versus 62% in CTL assay) than the HCVcp+F127 immunized animals. “Besides, total anti-core IgG and IgG1 levels were significantly higher in HCVcp + F127 immunized mice as compared to HCVcp + BCG vaccinated animals, indicating relatively higher efficacy of F127 for the stimulation of humoral and Th2-oriented immune responses”. Conclusions Results showed that HCVcp + BCG induced a moderate CTL and mixed Th1/Th2 immune responses with higher levels of cell proliferation and IFN-γ secretion, indicating that BCG may have a better outcome when formulated in HCVcp-based subunit vaccines. PMID:24348641

Hierarchical porous silver metal using Pluronic F-127 and graphene oxide as reinforcing agents for the reduction of o-nitroaniline to 1, 2-benzenediamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bano, Mustri; Ahirwar, Devendra; Thomas, Molly

An elegant method is used to prepare silver monoliths with Pluronic F-127(F-127) as sacrificial template by modified sol-gel method. Si nanoparticles (SiNPs) and graphene oxide (GO) are added in situ to Ag/F-127 hydrogel for the reduction of ο-nitroaniline (ο-NA) to 1, 2-benzenediamine. Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric analysis (TGA), Raman Spectroscopy, Powder X-Ray Diffraction (PXRD) analysis and Brunauer-Emmett-Teller (BET) Nitrogen adsorption techniques were used for characterization of monoliths. An epoch-making catalytic activity of Ag/F-127/GO monoliths is observed in the reduction of ο-NA to 1, 2-benzenediamine in presence of NaBH{sub 4} inmore » aqueous media. The catalyst Ag/F-127/GO took only 2 min which is the minimum time reported so far with significant rate constant claimed itself a leading catalyst for the reduction of ο-NA to 1,2-benzenediamine. Pseudo first order rate constant (k) and Turn over frequency (TOF) values are 0.231 min{sup −1} and 30.053×10{sup 19} molecules min{sup −1} respectively suggest that the catalyst has industrial importance. Recyclability and stability of Ag/F-127/GO catalyst are studied successfully up to 10 cycles. Energy of activation (E{sub a}), and thermodynamic parameters viz. activation enthalpy (ΔH{sup ≠}), activation Gibbs free energy (ΔG{sup ≠}), and entropy of activation (ΔS{sup ≠}) were also ascertained. Catalytic activities of Ag/F-127, Ag/F-127/Dextran, Ag/F-127/Trimethylbenzene (TMB), Ag/F-127/SiNPs, and Ag/F-127/Si/GO monoliths were also studied. - Graphical abstract: Significant catalytic activities of silver monoliths against the reduction of ο-NA to 1,2 benzenediamine. - Highlights: • A new catalyst synthesized Ag/F-127/GO for the reduction of ο- NA to 1, 2- benzenediamine took only 2 min. • Turn over frequency of as synthesized catalyst was 30.053×10{sup 19} molecules min{sup −1} claimed itself a leading catalyst. • Recyclability of the catalyst was up to 10 cycles. • The synthesis is non toxic, economically viable and environmentally benign.« less

Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

PubMed

Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

2014-10-01

A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release properties in the combined formulations. Our proof concept study shows that, the conversion of curcumin to a metal-organic supramolecular prodrug improved the solubility, stability and release profile of curcumin. The prodrug approach with the micellisation strategy appears to be more appropriate to deliver intact curcumin in the presence of ceramic particles of varying surface reactivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Biodegradable hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol), poly(ethylene glycol), and polycaprolactone as in situ thermogels.

PubMed

Li, Zibiao; Zhang, Zhongxing; Liu, Kerh Li; Ni, Xiping; Li, Jun

2012-12-10

This paper reports the synthesis and characterization of new hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol) (PPG), poly(ethylene glycol) (PEG), and polycaprolactone (PCL) segments as in situ thermogels. The hyperbranched poly(PPG/PEG/PCL urethane)s, termed as HBPEC copolymers, were synthesized from PPG-diol, PEG-diol, and PCL-triol by using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent. The compositions and structures of HBPEC copolymers were determined by GPC and 1H NMR spectroscopy. We carried out comparative studies of the new hyperbranched copolymers with their linear counterparts, the linear poly(PPG/PEG/PCL urethane) (LPEC) copolymer and Pluronic F127 PEG-PPG-PEG block copolymer, in terms of their self-assembly and aggregation behaviors and thermoresponsive properties. HBPEC copolymers were found to show thermoresponsive micelle formation and aggregation behaviors. Particularly, the lower critical solution temperature (LCST) of the copolymers was significantly affected by the copolymer architecture. HBPEC copolymers showed much lower LCST than LPEC, the linear counterpart. Our studies revealed that the effect of hyperbranch architecture was more prominent in the gelation of the copolymers. The aqueous solutions of HBPEC copolymers exhibited thermogelling behaviors at critical gelation concentrations (CGCs) ranging from 4.3 to 7.4 wt %. These values are much lower than those reported on other PCL-contained linear thermogelling copolymers and Pluronic F127 copolymer. In addition, the CGC of HBPEC copolymers is much lower than the control LPEC copolymer. More interestingly, at high temperatures, while LPEC and other linear thermogelling copolymers formed turbid sol, HBPEC formed a dehydrated gel. Our data suggest that these phenomena are caused by the hyperbranched structure of HBPEC copolymers, which could increase the interaction of copolymer branches and enhance the chain association through synergetic hydrogen bonding effect. The thermogelling behavior of HBPEC block copolymers was further evidenced by the 1H NMR molecular dynamic study and rheological study, which further support the above hypothesis. The hydrolytic degradation study showed that the HBPEC copolymer hydrogels are biodegradable under physiological conditions. Together with the good cell biocompatibility demonstrated by the cytotoxicity study, the new thermogelling copolymers reported in this paper could potentially be used as in situ-forming hydrogels for biomedical applications.

Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of posterior lumbar interbody fusion with cages for degenerative lumbar disease in osteoporosis patients by downregulating serum miR-155.

PubMed

Qu, Yang; Wang, Zhengming; Zhou, Haohan; Kang, Mingyang; Dong, Rongpeng; Zhao, Jianwu

2017-01-01

Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg pluronic nanoparticles). Serum miR-155 level was measured by real-time quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH), aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra) were measured. Weighted mean difference (WMD), relative risk (RR), complications, surgery infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores were used to evaluate therapeutic efficacy. After 1-month therapy, infection rates and side effects were lower in OG than those in PG (RR =0.64, 95% confidence interval [CI] [0.48, 0.84], P =0.001). The fusion rates were higher in OG than in PG (WMD =21.96, 95% CI [-0.24, 37.62], P =0.021). The JOA scores were higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], P =0.007), and no significant difference was found for the visual analog scale and Oswestry Disability Index. Serum levels of miR-155, ALT, AST, and IL-1β were lower while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased the levels of ALT, AST, and IL-1β and reduced the levels of SOD, GSH, and IL-1ra. In contrast, miR-155 inhibitor had reverse results. Therefore, ONAS has better improvement in complications and therapeutic effects on DLD by regulating serum miR-155.

Preparation of non-aggregating aqueous fullerenes in highly saline solutions with a biocompatible non-ionic polymer

NASA Astrophysics Data System (ADS)

Aich, Nirupam; Boateng, Linkel K.; Flora, Joseph R. V.; Saleh, Navid B.

2013-10-01

Size-tunable stable aqueous fullerenes were prepared with different concentrations of biocompatible block-copolymer pluronic (PA) F-127, ranging from 0.001% to 1% (w/v). Size uniformity increased with the increase in PA concentration, yielding optimum 58.8 ± 5.6 and 61.8 ± 5.6 nm nC60s and nC70s, respectively (0.10%w/v PA), as observed using a dynamic light scattering technique. Fullerene aqueous suspensions also manifested enhanced stability in saline solution, Dulbecco’s modified Eagle medium (DMEM), and Roswell Park Memorial Institute (RPMI) culture medium. Transmission electron microscopy was performed to elaborate on the morphology and size specificity of fullerene clusters. Physicochemical characterizations of the suspended fullerenes were performed through UV-vis spectroscopy and electrophoretic mobility measurements. PA molecules showed size restriction by encasement, as observed via molecular dynamics simulations. Such solubilization with controllable size and non-aggregating behavior can facilitate application enhancement and mechanistic environmental and toxicological studies of size-specific fullerenes.

Flexible Epoxy Resin Formed Upon Blending with a Triblock Copolymer through Reaction-Induced Microphase Separation

PubMed Central

Chu, Wei-Cheng; Lin, Wei-Sheng; Kuo, Shiao-Wei

2016-01-01

In this study, we used diglycidyl ether bisphenol A (DGEBA) as a matrix, the ABA block copolymer poly(ethylene oxide–b–propylene oxide–b–ethylene oxide) (Pluronic F127) as an additive, and diphenyl diaminosulfone (DDS) as a curing agent to prepare flexible epoxy resins through reaction-induced microphase separation (RIMPS). Fourier transform infrared spectroscopy confirmed the existence of hydrogen bonding between the poly(ethylene oxide) segment of F127 and the OH groups of the DGEBA resin. Small-angle X-ray scattering, atomic force microscopy, and transmission electron microscopy all revealed evidence for the microphase separation of F127 within the epoxy resin. Glass transition temperature (Tg) phenomena and mechanical properties (modulus) were determined through differential scanning calorimetry and dynamic mechanical analysis, respectively, of samples at various blend compositions. The modulus data provided evidence for the formation of wormlike micelle structures, through a RIMPS mechanism, in the flexible epoxy resin upon blending with the F127 triblock copolymer. PMID:28773571

Effects of Liposomes Contained in Thermosensitive Hydrogels as Biomaterials Useful in Neural Tissue Engineering.

PubMed

Olguín, Yusser; Campos, Cristian; Catalán, Javiera; Velásquez, Luís; Osorio, Fernando; Montenegro, Iván; Madrid, Alejandro; Acevedo, Cristian

2017-09-22

Advances in the generation of suitable thermosensitive hydrogels for the delivery of cells in neural tissue engineering demonstrate a delicate relationship between physical properties and capabilities to promote cell proliferation and differentiation. To improve the properties of these materials, it is possible to add liposomes for the controlled release of bioactive elements, which in turn can affect the physical and biological properties of the hydrogels. In the present investigation, different hydrogels based on Pluronic F127 have been formulated with the incorporation of chitosan and two types of liposomes of two different sizes. The rheological and thermal properties and their relation with the neurite proliferation and growth of the PC12 cell line were evaluated. Our results show that the incorporation of liposomes modifies the properties of the hydrogels dependent on the concentration of chitosan and the lipid type in the liposomes, which directly affect the capabilities of the hydrogels to promote the viability and differentiation of PC12 cells.

Synthesis of nitrogen-doped mesoporous carbon from polyaniline with an F127 template for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Xin, Guoxiang; Wang, Yanhui; Jia, Shaopei; Tian, Pengfei; Zhou, Shuyu; Zang, Jianbing

2017-11-01

N-doped mesoporous carbons (N-MCs) were synthesized via the oxypolymerization of aniline with a Pluronic F127 template, sintering at 850 °C in N2 atmosphere, and activation in a KOH solution. The contrast experiments were carried out without the addition of F127 and the obtained sample was defined as N-Cs. The Brunaner-Emmett-Teller measurement, pore size distribution measurements, transmission electron microscopy, and X-ray photoelectron spectroscopy of N-MCs and N-Cs were performed. The specific areas of the N-MCs and N-Cs reached 721 and 394 m2 g-1, respectively. The specific capacitances of the N-MCs and N-Cs were as high as 318 and 106 F g-1 at 0.2 A g-1. The cycle life of N-MCs at different current densities was above 96% after 5000 cycles of charging and discharging, indicating that the N-MCs had excellent cycle stability.

Incessant formation of chain-like mesoporous silica with a superior binding capacity for mercury.

PubMed

Ravi, S; Selvaraj, M

2014-04-14

A novel incessant formation of chain like mesoporous silica (ICMS) has been easily materialized using a mixed surfactant (Pluronic P123 and FC-4) as a structuring reagent in conjunction with a thiol precursor (3-MPS) through a one-pot synthetic method. A particular thiol concentration facilitated the interaction of the micelle head groups to form long-chain micelles, where FC-4 enhanced further growth. The rapid interactions of the micelles and the condensation of silicic acid and its oligomeric derivatives by coordinating 3-MPS through hydrogen bonding interactions leads to form ICMS. The characterization results for the ICMS illustrated that it has an ordered hexagonal pore geometry. The capability of the ICMS for Hg(2+) adsorption was extensively studied under different optimal parameters and the adsorption isothermal values clearly fit with the Langmuir and Freundlich isothermal plots. This novel material exhibited an unprecedentedly high binding affinity toward even microgram levels of mercury ions in wastewater, compared to other thiol-based mesoporous silica.

Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications.

PubMed

Elnaggar, Yosra S R; El-Refaie, Wessam M; El-Massik, Magda A; Abdallah, Ossama Y

2014-04-28

Conventional carriers for skin delivery encounter obstacles of drug leakage, scanty permeation and low entrapment efficiency. Phospholipid nanogels have recently been recognized as prominent delivery systems to circumvent such obstacles and impart easier application. The current review provides an overview on different types of lecithin nanostructured gels, with particular emphasis on liposomal versus microemulsion gelled systems. Liposomal gels investigated encompassed classic liposomal hydrogel, modified liposomal gels (e.g. Transferosomal, Ethosomal, Pro-liposomal and Phytosomal gels), Microgel in liposomes (M-i-L) and Vesicular phospholipid gel (VPG). Microemulsion gelled systems encompassed Lecithin microemulsion-based organogels (LMBGs), Pluronic lecithin organogels (PLOs) and Lecithin-stabilized microemulsion-based hydrogels. All systems were reviewed regarding matrix composition, state of art, characterization and updated applications. Different classes of lecithin nanogels exhibited crucial impact on transdermal delivery regarding drug permeation, drug loading and stability aspects. Future perspectives of this theme issue are discussed based on current laboratory studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Ordered Materials via Additive Driven Assembly and Reaction using Surfactant-Based Templates

NASA Astrophysics Data System (ADS)

Beaulieu, Michael R.; Daga, Vikram K.; Lesser, Alan J.; Watkins, James J.

2011-03-01

We recently reported (1) the ordering behavior of Pluronic surfactant melts through the addition of aromatic additives with hydrogen bond donating groups, which exhibit selective interactions with the polyethylene oxide (PEO) block. The ordered blends had domain sizes ranging from 12 to 16 nm at additive loadings up to 80%.The goal of this work is to utilize condensation chemistries based on the functionality of similar additives, to yield ordered composite materials that could be used for applications involving membranes or dielectric materials. The structure of the blends and composites are determined by small angle x-ray scattering, which indicates that the ordered structure is preserved following reaction of the additives. Differential scanning calorimetry indicates that an increase in additive loading causes a decrease in the melting temperature and enthalpy of melting of the PEO, which demonstrates that the interaction between the PEO segments and the additive is strong. (1) Daga, V.K., Watkins, J. J. Macromolecules, ASAP.

Low-Temperature Fluorination of Soft-Templated Mesoporous Carbons for a High-Power Lithium/Carbon Fluoride Battery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fulvio, Pasquale F.; Brown, Suree S.; Adcock, Jamie

Soft-templated mesoporous carbons and activated mesoporous carbons were fluorinated using elemental fluorine between room temperature and 235 °C. The mesoporous carbons were prepared via self-assembly synthesis of phloroglucinol–formaldehyde as a carbon precursor in the presence of triblock ethylene oxide–propylene oxide–ethylene oxide copolymer BASF Pluronic F127 as the template. The F/C ratios ranged from ~0.15 to 0.75 according to gravimetric, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy analysis. Materials have mesopore diameters up to 11 nm and specific surface areas as high as 850 m² g⁻¹ after fluorination as calculated from nitrogen adsorption isotherms at -196 °C. Furthermore, the materialsmore » exhibit higher discharge potentials and energy and power densities as well as faster reaction kinetics under high current densities than commercial carbon fluorides with similar fluorine contents when tested as cathodes for Li/CF x batteries.« less

Low-Temperature Fluorination of Soft-Templated Mesoporous Carbons for a High-Power Lithium/Carbon Fluoride Battery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fulvio, Pasquale F; Dai, Sheng; Guo, Bingkun

Soft-templated mesoporous carbons and activated mesoporous carbons were fluorinated using elemental fluorine between room temperature and 235 C. The mesoporous carbons were prepared via self-assembly synthesis of phloroglucinol formaldehyde as a carbon precursor in the presence of triblock ethylene oxide propylene oxide ethylene oxide copolymer BASF Pluronic F127 as the template. The F/C ratios ranged from 0.15 to 0.75 according to gravimetric, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy analysis. Materials have mesopore diameters up to 11 nm and specific surface areas as high as 850 m2 g 1 after fluorination as calculated from nitrogen adsorption isotherms at 196more » C. Furthermore, the materials exhibit higher discharge potentials and energy and power densities as well as faster reaction kinetics under high current densities than commercial carbon fluorides with similar fluorine contents when tested as cathodes for Li/CFx batteries.« less

Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.

PubMed

Perera, Reshani H; Wu, Hanping; Peiris, Pubudu; Hernandez, Christopher; Burke, Alan; Zhang, Helen; Exner, Agata A

2017-01-01

The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N,N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2±25.2nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Facile fabrication of high-quality Ag/PS coaxial nanocables based on the mixed mode of soft/hard templates

PubMed Central

Wan, Mimi; Zhao, Wenbo; Peng, Fang; Wang, Qi; Xu, Ping; Mao, Chun; Shen, Jian

2016-01-01

A new kind of high-quality Ag/PS coaxial nanocables can be facilely synthesized by using soft/hard templates method. In order to effectively introduce Ag sources into porous polystyrene (PS) nanotubes which were trapped in porous anodic aluminum oxide (AAO) hard template, Pluronic F127 (F127) was used as guiding agent, soft template and reductant. Meanwhile, ethylene glycol solution was also used as solvent and co-reducing agent to assist in the formation of silver nanowires. The influences of concentration of F127 and reducing reaction time on the formation of Ag/PS coaxial nanocables were discussed. Results indicated that the high-quality Ag/PS coaxial nanocables can be obtained by the mixed mode of soft/hard templates under optimized conditions. This strategy is expected to be extended to design more metal/polymer coaxial nanocables for the benefit of creation of complex and functional nanoarchitectures and components. PMID:27477888

Continuously manufactured magnetic polymersomes - a versatile tool (not only) for targeted cancer therapy

NASA Astrophysics Data System (ADS)

Bleul, Regina; Thiermann, Raphael; Marten, Gernot U.; House, Michael J.; Pierre, Timothy G. St.; Häfeli, Urs O.; Maskos, Michael

2013-11-01

Micromixer technology was used to prepare polymeric vesicles (Pluronic® L-121) dual loaded with the anti-cancer drug camptothecin and magnetic nanoparticles. Successful incorporation of the magnetic nanoparticles was confirmed by transmission electron microscopy. Dynamic light scattering measurements showed a relatively narrow size distribution of the hybrid polymersomes. Camptothecin polymersomes reduced the cell viability of prostate cancer cells (PC-3) measured after 72 h significantly, while drug-free polymersomes showed no cytotoxic effects. Covalent attachment of a cancer targeting peptide (bombesin) as well as a fluorescent label (Alexa Fluor® 647) to the hybrid polymersomes was performed and specific cell binding and internalization were shown by flow cytometry and confocal microscopy. Relaxometry measurements clearly demonstrated the capacity of magnetic polymersomes to generate significant T2-weighted MRI contrast and potentially allow for direct monitoring of the biodistribution of the polymersomes. Micromixer technology as an easy, fast and efficient way to manufacture hybrid polymersomes as theranostic drug delivery devices is a further step from basic research to personalized medicine.

Optical, colloidal and biological properties of up-converting nanoparticles embedded in polyester nanocarriers

NASA Astrophysics Data System (ADS)

Wawrzyńczyk, Dominika; Kulbacka, Julita; Bazylińska, Urszula

2017-08-01

We have investigated the change in optical properties and biocompatibility of up-converting NaYF4 nanoparticles (NPs) upon encapsulation inside the polyester nanocarriers (NCs) stabilized by Crempophor RH40 (CRH40), poly(D,L-lactide) (PLA), Pluronic P123 (P123). NaYF4:Er3+,Yb3+ NPs showed intense green and red emission, and upon encapsulation the increase of red band in respect to green one was observed, with no luminescence lifetime shortening. Obtained NCs showed prolonged colloidal stability and protective effect of the polymer shell simultaneously preserving the high emission efficiency of nanoparticles embedded within the silicon oil (SO) core. Based on emission spectra, kinetic measurements and cytotoxicity studies upon human malignant melanoma Me45 cell line we have shown the advantages of using polyester NCs as containers for the up-converting NPs. Due to the possibility of co-encapsulation of photosensitizers the obtained nanocarriers showed potential for application in theranostics.

In vivo nanotoxicology of hybrid systems based on copolymer/silica/anticancer drug

NASA Astrophysics Data System (ADS)

Silveira, C. P.; Paula, A. J.; Apolinário, L. M.; Fávaro, W. J.; Durán, N.

2015-05-01

One of the major problems in cancer therapies is the high occurrence of side effects intrinsic of anticancer drugs. Doxorrubicin is a conventional anticancer molecule used to treat a wide range of cancer, such as breast, ovarian and prostate. However, its use is associated with a number of side effects like multidrug resistance and cardiotoxicity. The association with nanomaterials has been considered in the past decade to overcome the high toxicity of these drugs. In this context, mesoporous silica nanoparticles are great candidates to be used as carriers once they are very biocompatible. Taking into account the combination of nanoparticles and doxorrubicin, we treated rats with chemically induced prostate cancer with systems based on mesoporous silica nanoparticles and a thermoreversible block copolymer (Pluronic F-127) containing doxorrubicin. Preliminary results show a possible improvement in tumor conditions proportional to the concentration of the nanoparticles, opening a perspective to use mesoporous silica nanoparticles as carrier for doxorrubicin in prostate cancer treatment.

Effects of Liposomes Contained in Thermosensitive Hydrogels as Biomaterials Useful in Neural Tissue Engineering

PubMed Central

Olguín, Yusser; Campos, Cristian; Catalán, Javiera; Velásquez, Luís; Osorio, Fernando; Montenegro, Iván; Madrid, Alejandro; Acevedo, Cristian

2017-01-01

Advances in the generation of suitable thermosensitive hydrogels for the delivery of cells in neural tissue engineering demonstrate a delicate relationship between physical properties and capabilities to promote cell proliferation and differentiation. To improve the properties of these materials, it is possible to add liposomes for the controlled release of bioactive elements, which in turn can affect the physical and biological properties of the hydrogels. In the present investigation, different hydrogels based on Pluronic F127 have been formulated with the incorporation of chitosan and two types of liposomes of two different sizes. The rheological and thermal properties and their relation with the neurite proliferation and growth of the PC12 cell line were evaluated. Our results show that the incorporation of liposomes modifies the properties of the hydrogels dependent on the concentration of chitosan and the lipid type in the liposomes, which directly affect the capabilities of the hydrogels to promote the viability and differentiation of PC12 cells. PMID:28937646

An abrasion-resistant and broadband antireflective silica coating by block copolymer assisted sol-gel method.

PubMed

Zou, Liping; Li, Xiaoguang; Zhang, Qinghua; Shen, Jun

2014-09-02

A double-layer broadband antireflective (AR) coating was prepared on glass substrate via sol-gel process using two kinds of acid-catalyzed TEOS-derived silica sols. The relative dense layer with a porosity of ∼10% was obtained from an as-prepared sol, while the porous layer with a porosity of ∼55% was from a modified one with block copolymer (BCP) Pluronic F127 as template which results in abundant ordered mesopores. The two layers give rise to a reasonable refractive index gradient from air to the substrate and thus high transmittance in a wide wavelength range, and both of them have the same tough skeleton despite different porosity, for which each single-layer and the double-layer coatings all behaved well in the mechanical property tests. The high transmittance and the strong ability of resisting abrasion make this coating promising for applications in some harsh conditions. In addition, the preparation is simple, low-cost, time-saving, and flexible for realizing the optical property.

Novel reverse osmosis membranes composed of modified PVA/Gum Arabic conjugates: Biofouling mitigation and chlorine resistance enhancement.

PubMed

Falath, Wail; Sabir, Aneela; Jacob, Karl I

2017-01-02

A novel crosslinked Poly (vinyl alcohol) (PVA) reverse osmosis (RO) thin film membrane conjugated with Gum Arabic (GA) with superb performance and features was synthesized for water desalination. RO membrane desalination parameters, such as hydrophilicity, surface roughness, water permeability, salt rejection, Chlorine resistance and biofouling resistance were evaluated using a dead end RO filtration unit. The incorporation of Pluronic F127 and the conjugation of Gum Arabic improved the overall RO performance of the membranes. This study has shown that the membrane PVA-GA-5 that contains 0.9wt% Gum Arabic provided excellent permeation, salt rejection, Chlorine and biofouling resistance and mechanical strength. The most remarkable result to arise from this research is that the overall RO performance enhancement has been achieved while utilizing PVA/Gum Arabic as a separation layer without the use of a substrate, which eliminates negative effects associated with the use of a substrate like internal concentration polarization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microwave-assisted synthesis of porous carbon-titania and highly crystalline titania nanostructures.

PubMed

Parker, Alison; Marszewski, Michal; Jaroniec, Mietek

2013-03-01

Porous carbon-titania and highly crystalline titania nanostructured materials were obtained through a microwave-assisted one-pot synthesis. Resorcinol and formaldehyde were used as carbon precursors, triblock copolymer Pluronic F127 as a stabilizing agent, and titanium isopropoxide as a titania precursor. This microwave-assisted one-pot synthesis involved formation of carbon spheres according to the recently modified Stöber method followed by hydrolysis and condensation of titania precursor. This method afforded carbon-titania composite materials containing anatase phase with specific surface areas as high as 390 m(2) g(-1). The pure nanostructured titania, obtained after removal of carbon through calcination of the composite material in air, was shown to be the anatase phase with considerably higher degree of crystallinity and the specific surface area as high as 130 m(2) g(-1). The resulting titania, because of its high surface area, well-developed porosity, and high crystallinity, is of great interest for catalysis, water treatment, lithium batteries, and other energy-related applications.

Carbon nanotube thin film strain sensors: comparison between experimental tests and numerical simulations

NASA Astrophysics Data System (ADS)

Lee, Bo Mi; Loh, Kenneth J.

2017-04-01

Carbon nanotubes can be randomly deposited in polymer thin film matrices to form nanocomposite strain sensors. However, a computational framework that enables the direct design of these nanocomposite thin films is still lacking. The objective of this study is to derive an experimentally validated and two-dimensional numerical model of carbon nanotube-based thin film strain sensors. This study consisted of two parts. First, multi-walled carbon nanotube (MWCNT)-Pluronic strain sensors were fabricated using vacuum filtration, and their physical, electrical, and electromechanical properties were evaluated. Second, scanning electron microscope images of the films were used for identifying topological features of the percolated MWCNT network, where the information obtained was then utilized for developing the numerical model. Validation of the numerical model was achieved by ensuring that the area ratios (of MWCNTs relative to the polymer matrix) were equivalent for both the experimental and modeled cases. Strain sensing behavior of the percolation-based model was simulated and then compared to experimental test results.

Microencapsulation of essential oil for insect repellent in food packaging system.

PubMed

Chung, Seong Kyun; Seo, Ji Yeon; Lim, Jung Hoon; Park, Hyung Hwan; Yea, Myeong Jai; Park, Hyun Jin

2013-05-01

Microcapsules containing thyme oil were prepared by in situ polymerization, using melamine-formaldehyde prepolymer as a wall material and 3 different emulsifiers (pluronic F-127, tween 80, and sodium lauryl sulfate [SLS]). The general characteristics and release behavior of microcapsules, and their repellent effect against insects were investigated. The morphology of microcapsules using SLS was spherical shape with smooth surface. Microcapsules began to degrade at 150 °C. The particle size ranged from 1 to 10 μm and the loading efficiency of thyme oil was clearly affected by the emulsifier type. The highest loading efficiency appeared in microcapsules using SLS, which have good thermal resistance and smooth surface. The release rate of thyme oil from microcapsules was not only dependent on the storage temperature but also emulsifier type and microcapsules showed the sustained release properties for a long time. Diets, which were mixed with encapsulated thyme oil, expressed high insect repellent efficacy over 90% for 4 wk. © 2013 Institute of Food Technologists®

Interaction of triblock co-polymer micelles with phospholipid-bilayer: a spectroscopic investigation using a potential chloride channel blocker.

PubMed

Ganguly, Aniruddha; Ghosh, Soumen; Guchhait, Nikhil

2015-03-07

Interaction of a potential chloride channel blocker, 9-methyl anthroate (9-MA), has been studied with zwitterionic l-α-phosphatidylcholine (egg-PC) lipid vesicles, which ascertains the utility of the drug as an efficient molecular reporter for probing the microheterogeneous environment of lipid-bilayers. The effect of a non-ionic triblock co-polymer P123 on the stability of these drug-bound lipid-bilayers has also been investigated by means of steady state and time-resolved spectroscopic techniques exploiting the fluorescence properties of the drug. Experimental results reveal that the addition of P123 to the drug-bound lipid results in a preferential complexation of the drug with the Pluronic leaving the lipid vesicles aside, which has been attributed to a substantially stronger binding interaction of the drug with P123 than that with egg-PC. The result is of potential interest from a medical perspective owing to the context of excess drug desorption from bio-membranes.

Water-Soluble Spinel Ferrites by a Modified Polyol Process as Contrast Agents in MRI

NASA Astrophysics Data System (ADS)

Basina, Georgia; Tzitzios, Vasilis; Niarchos, Dimitris; Li, Wanfeng; Khurshid, Hafsa; Mao, Hui; Hadjipanayis, Costas; Hadjipanayis, George

2010-12-01

Magnetic nanoparticles have recently been very attractive for biomedical applications. In this study, we have synthesized ferrite nanoparticles for application as contrast agents in MRI experiments. Fe3O4 and MnFe2O4 spinel ferrites with a mean size of 11-12 nm, were prepared by a modified polyol route in commercially available polyethylene glycol with molecular weight 600 (PEG-600). The reaction takes place in the presence of water soluble and non-toxic tri-block copolymer known as Pluronic® F-127 (PEO100-PPO65-PEO100). The nanoparticles have saturation magnetization values of 52 and 68 emu/g for MnFe2O4 and Fe3O4, respectively. Both the Fe3O4, and MnFe2O4 nanoparticles make stable solutions in water known as ferrofluids. Preliminary data demonstrated the capability of these nanoparticles to induce imaging contrast in T2 weighted MRI experiments, making these materials suitable for biomedical applications such as medical MRI.

Simple control of surface topography of gold nanoshells by a surfactant-less seeded-growth method.

PubMed

Topete, Antonio; Alatorre-Meda, Manuel; Villar-Álvarez, Eva M; Cambón, Adriana; Barbosa, Silvia; Taboada, Pablo; Mosquera, Víctor

2014-07-23

We report the synthesis of branched gold nanoshells (BGNS) through a seeded-growth surfactant-less method. This was achieved by decorating chitosan-Pluronic F127 stabilized poly(lactic-co-gycolic) acid nanoparticles (NPs) with Au seeds (NP-seed), using chitosan as an electrostatic self-assembling agent. Branched shells with different degrees of anisotropy and optical response were obtained by modulating the ratios of HAuCl4/K2CO3 growth solution, ascorbic acid (AA) and NP-seed precursor. Chitosan and AA were crucial in determining the BGNS size and structure, acting both as coreductants and structure directing growth agents. Preliminary cytotoxicity experiments point to the biocompatibility of the obtained BGNS, allowing their potential use in biomedical applications. In particular, these nanostructures with "hybrid" compositions, which combine the features of gold nanoshells and nanostars showed a better performance as surface enhanced Raman spectroscopy probes in detecting intracellular cell components than classical smoother nanoshells.

Versatility of Evaporation-Induced Self-Assembly (EISA) Method for Preparation of Mesoporous TiO2 for Energy and Environmental Applications

PubMed Central

Mahoney, Luther; Koodali, Ranjit T.

2014-01-01

Evaporation-Induced Self-Assembly (EISA) method for the preparation of mesoporous titanium dioxide materials is reviewed. The versatility of EISA method for the rapid and facile synthesis of TiO2 thin films and powders is highlighted. Non-ionic surfactants such as Pluronic P123, F127 and cationic surfactants such as cetyltrimethylammonium bromide have been extensively employed for the preparation of mesoporous TiO2. In particular, EISA method allows for fabrication of highly uniform, robust, crack-free films with controllable thickness. Eleven characterization techniques for elucidating the structure of the EISA prepared mesoporous TiO2 are discussed in this paper. These many characterization methods provide a holistic picture of the structure of mesoporous TiO2. Mesoporous titanium dioxide materials have been employed in several applications that include Dye Sensitized Solar Cells (DSSCs), photocatalytic degradation of organics and splitting of water, and batteries. PMID:28788590

Synthesis of magnetic ordered mesoporous carbon (Fe-OMC) adsorbent and its evaluation for fuel desulfurization

NASA Astrophysics Data System (ADS)

Farzin Nejad, N.; Shams, E.; Amini, M. K.

2015-09-01

In this work, magnetic ordered mesoporous carbon adsorbent was synthesized using soft templating method to adsorb sulfur from model oil (dibenzothiophene in n-hexane). Through this research, pluronic F-127, resorcinol-formaldehyde and hydrated iron nitrate were respectively used as soft template, carbon source and iron source. The adsorbent was characterized by X-ray diffraction, nitrogen adsorption-desorption isotherm and transmission electron microscopy. Nitrogen adsorption-desorption measurement revealed the high surface area (810 m2 g-1), maxima pore size of 3.3 nm and large pore volume (1.01 cm3 g-1) of the synthesized sample. The adsorbent showed a maximum adsorption capacity of 111 mg dibenzothiophene g-1 of adsorbent. Sorption process was described by the pseudo-second-order rate equation and could be better fitted by the Freundlich model, showing the heterogeneous feature of the adsorption process. In addition, the adsorption capacity of regenerated adsorbent was 78.6% of the initial level, after five regeneration cycles.

New infrared-assisted method for sol-gel derived ZnO:Ag thin films: Structural and bacterial inhibition properties.

PubMed

González-Penguelly, Brenely; Morales-Ramírez, Ángel de Jesús; Rodríguez-Rosales, Miriam Guadalupe; Rodríguez-Nava, Celestino Odín; Carrera-Jota, María Luz

2017-09-01

A new sol-gel method, based on crystallization with Infrared heating, was developed to obtain ZnO:Ag thin films. The common sol, with zinc acetate as precursor and silver nitrate as doping source (1, 3 and 5 % molar), isopropanol and distilled water as solvents and monoethanolamine as stabilizer agent; was modified with Pluronic F127 and diethylene glycol as rheological agents, and with urea as fuel to produce enough energy to the combustion and to promote the crystallization process. Later, Corning glass-substrates were dipped into the sol at a constant speed of 3mms -1 . To provide the necessary energy for obtaining the hexagonal ZnO structure of the coatings during the drying and consolidation process, instead of using the common furnace heat-treatment, the films were heated by means of an infrared (IR) ceramic lamp (800W) for 15, 30, 45, 60 and 180 minutes, and the effect of this annealing method was analyzed. The structural properties were examined by means of X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), whereas morphology was studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The examination revealed a homogeneous distribution of particles with the characteristic pores of pluronic F127, and the coating roughness had an average value of 100nm by AFM. To evaluate the effect on the number of dipping cycles and the IR-treatment on the thickness, ellipsometry results for 1, 3 and 5 deposits were analyzed and showed increments of 780, 945 and 1082nm, respectively. Finally, to test of the antibacterial activity, instead of the common one-microorganism approach, environmental microorganisms that grow with expose of the broth to the ambient conditions were employed (microbial consortium), which is a real environmental condition. The biological test was carried out by kinetic growth inhibition (optical density) of heterotrophic bacteria in culture liquid media under conditions of light, light-dark and darkness, to analyze the effect of light. A significance reduction in growth was obtained for doped coatings with silver in comparison with the control ZnO substrate. Furthermore, the analysis bacteria growth inhibition on a solid surface showed that the films effectively present antibacterial activity. The best result was obtained with ZnO:Ag 1% in light conditions, about 67%, but all the coatings inhibited the bacterial activity. Copyright © 2017 Elsevier B.V. All rights reserved.

A bifunctional electrolyte additive for separator wetting and dendrite suppression in lithium metal batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Hao; Xie, Yong; Xiang, Hongfa

Reformulation of electrolyte systems and improvement of separator wettability are vital to electrochemical performances of rechargeable lithium (Li) metal batteries, especially for suppressing Li dendrites. In this work we report a bifunctional electrolyte additive that improves separator wettability and suppresses Li dendrite growth in LMBs. A triblock polyether (Pluronic P123) was introduced as an additive into a commonly used carbonate-based electrolyte. It was found that addition of 0.2~1% (by weight) P123 into the electrolyte could effectively enhance the wettability of polyethylene separator. More importantly, the adsorption of P123 on Li metal surface can act as an artificial solid electrolyte interphasemore » layer and contribute to suppress the growth of Li dendrites. A smooth and dendritic-free morphology can be achieved in the electrolyte with 0.2% P123. The Li||Li symmetric cells with the 0.2% P123 containing electrolyte exhibit a relatively stable cycling stability at high current densities of 1.0 and 3.0 mA cm-2.« less

Highly Loaded Mesoporous Silica/Nanoparticle Composites and Patterned Mesoporous Silica Films

NASA Astrophysics Data System (ADS)

Kothari, Rohit; Hendricks, Nicholas R.; Wang, Xinyu; Watkins, James J.

2014-03-01

Novel approaches for the preparation of highly filled mesoporous silica/nanoparticle (MS/NP) composites and for the fabrication of patterned MS films are described. The incorporation of iron platinum NPs within the walls of MS is achieved at high NP loadings by doping amphiphilic poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (Pluronic®) copolymer templates via selective hydrogen bonding between the pre-synthesized NPs and the hydrophilic portion of the block copolymer. The MS is then synthesized by means of phase selective condensation of tetraethylorthosilicate (TEOS) within the NP loaded block copolymer templates dilated with supercritical carbon dioxide (scCO2) followed by calcination. For patterned films, microphase separated block copolymer/small molecule additive blends are patterned using UV-assisted nanoimprint lithography. Infusion and condensation of a TEOS within template films using ScCO2 as a processing medium followed by calcination yields the patterned MS films. Scanning electron microscopy is used characterize pattern fidelity and transmission electron microscopy analysis confirms the presence of the mesopores. Long range order in nanocomposites is confirmed by low angle x-ray diffraction.

Nd-doped Bi2O3 nanocomposites: simple synthesis and improved photocatalytic activity for hydrogen production under visible light

NASA Astrophysics Data System (ADS)

Al-Namshah, Khadijah S.; Mohamed, Reda M.

2018-04-01

Bi2O3 has 2.4 eV band gap energy, which means it absorb in visible region. Though the photocatalytic activity of Bi2O3 is extremely little due to rapid rate of photogenerated electron-hole recombination. To face the economical and practical needs, the photocatalytic efficiency of Bi2O3 should be upgraded. In this paper, this was achieved by addition of neodymium to Bi2O3 nanosheets and Nd/Bi2O3 nanocomposites were prepared by a easy process at room temperature using a surfactant of Pluronic F127. The Bi2O3 nanosheets and Nd/Bi2O3 nanocomposites were investigated by many tools. The photocatalytic activity of Nd/Bi2O3 samples is better than Bi2O3 due to reduced band gap and reduced electron-hole recombination of Bi2O3 with addition of neodymium. In addition, Nd/Bi2O3 nanocomposites exhibit photocatalytic stability for hydrogen production which enables it to be reused on other occasions also.

Investigation of the Evolution of Crystal Size and Shape during Temperature Cycling and in the Presence of a Polymeric Additive Using Combined Process Analytical Technologies

PubMed Central

2017-01-01

Crystal size and shape can be manipulated to enhance the qualities of the final product. In this work the steady-state shape and size of succinic acid crystals, with and without a polymeric additive (Pluronic P123) at 350 mL, scale is reported. The effect of the amplitude of cycles as well as the heating/cooling rates is described, and convergent cycling (direct nucleation control) is compared to static cycling. The results show that the shape of succinic acid crystals changes from plate- to diamond-like after multiple cycling steps, and that the time required for this morphology change to occur is strongly related to the type of cycling. Addition of the polymer is shown to affect both the final shape of the crystals and the time needed to reach size and shape steady-state conditions. It is shown how this phenomenon can be used to improve the design of the crystallization step in order to achieve more efficient downstream operations and, in general, to help optimize the whole manufacturing process. PMID:28867966

Synthesis, characterization and photoactivity of bi-crystalline mesoporous TiO2

NASA Astrophysics Data System (ADS)

Nguyen, Dongthanh; Wang, Wei; Long, Haibo; Ru, Hongqiang

2016-03-01

Mesoporous titania (meso-TiO2) has received extensive attention owing to its versatile potential applications. This paper reports a low-temperature templating approach for the fabrication of meso-TiO2 using the peroxo titanic acid (PTA) sol as precursor and Pluronic P123 as nonionic template. The TGA, XRD, N2 sorption, FE-SEM and HRTEM were used to characterize the obtained samples. The results showed that meso-TiO2 with high surface area up to 163 m2·g-1 and large pore volume of 0.65 cm3·g-1 can be obtained. The mesopore sizes can be varied between 13 and 20 nm via this synthesis approach. The amount of P123 and the calcination conditions were found to have great influence on the mesoporous and crystalline structures of meso-TiO2. The photocatalytic activity testing clearly shows that the high surface area and bi-crystallinity phases of meso-TiO2 play important roles in enhancing photocatalytic properties of meso-TiO2 in photo-decomposing Rhodamine B in water.

Simple D-A-D Structural Bisbithiophenyl Diketopyrrolopyrrole (TDPP) as Efficient Bioimaging and Photothermal Agents.

PubMed

Zong, Shan; Wang, Xin; Lin, Wenhai; Liu, Shi; Zhang, Wei

2018-06-20

Design and synthesis of biocompatible and multi-functional photothermal agents is crucial for effective cancer phototherapy. In order to achieve this ambition, simple D-A-D structural bisbithiophenyl diketopyrrolopyrrole (TDPP) was fabricated. In this molecule, the donor, 2-thiophenylboric acid, was conjugated via Suzuki coupling reaction, which could expand the emission wavelength to the red region of the spectrum. TDPP could self-assemble into stable and uniform nanoparticles (TDPP NPs) in the assistant of amphiphilic Pluronic F-127 polymer. Exposing the TDPP NPs (100 µg/mL) aqueous dispersion to 638 nm (0.61 W/cm2) laser irradiation resulted in a temperature elevation of approximately 30 oC within 5 min, which is high enough for inducing the cytotoxicity and tumor inhibition. Because of the bathochromic shift absorption of TDPP NPs in water, TDPP NPs could also act as a contrast agent for near-infrared fluorescence imaging (NIRF) to visualize the drug distribution in vivo. Coupled with the infrared thermal imaging properties of the photothermal agent, TDPP NPs were proved to be a multifunctional theranostic agent for dual-modal imaging-guided phototherapy.

A low cost preparation of WO3 nanospheres film with improved thermal stability of gasochromic and its application in smart windows

NASA Astrophysics Data System (ADS)

Zhou, Baoyu; Feng, Wei; Gao, Guohua; Wu, Guangming; Chen, Yue; Li, Wen

2017-11-01

Porous WO3 nanospheres film was successfully synthesized by employing a low-cost and facile template-assisted sol-gel method. The effects of template agent (Pluronic F127) on structure, morphology and specific surface area were systematically studied by Fourier transform infrared (FTIR), x-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and N2 physisorption. It was found that F127 played a significant role in governing the morphology of WO3 sol clusters, and the optimal post-processing for ‘naked’ WO3 nanospheres film is acetone extraction and subsequent annealing treatment at 350 °C. As anticipated, the relative fast coloring/bleaching rates of WO3 nanospheres film are believed to be the results of porous microstructure and nanocrystalline, where provides much surface active position (166 m2 g-1) and shortens the proton diffusion distance. We believe that this unique approach to synthesize nanospheres structure may has beneficial effects on applications which also are based on insertion/extraction and diffusion abilities, such as supercapacitor, batteries and gas sensors.

Effect of surface coating of KYb2F7:Tm3+ on optical properties and biomedical applications

NASA Astrophysics Data System (ADS)

Pedraza, Francisco J.; Avalos, Julio C.; Yust, Brian G.; Tsin, Andrew; Sardar, Dhiraj K.

2016-09-01

This project aims to provide an insight on the effects of biocompatible polymers on the optical properties and the nanoparticle-cell interaction of KYb2F7:Tm3+ nanocrystals that exhibit strong near infrared (NIR) fluorescence. KYb2F7:Tm3+ nanocrystals were synthesized with a diameter of 20-30 nm and surface modified with poly(ethylene glycol), Pluronic® F-127, and poly(N-vinylpyrrolidone), due to the associated advantages. Some of these include biocompatibility and biodistribution in the instance of agglomeration and hydrophobicity as well as the addition of a targeting agent and drug loading by further functionalization. Despite the decrease in fluorescence intensity induced by the surface modification, thulium’s emission fingerprint was easily detected. Moreover, surface modified KYb2F7:Tm3+ nanocrystals failed to induce a toxic response on endothelial cells following a 24 h uptake period up to concentrations of 100 μg ml-1. In vitro toxicity and confocal imaging have demonstrated the versatility of these NIR fluorescence nanocrystals in biomedical imaging, drug delivery, and photodynamic therapy.

Iron oxide nanoparticles as dielectric and piezoelectric enhancers for silicone elastomers

NASA Astrophysics Data System (ADS)

Iacob, Mihail; Tugui, Codrin; Tiron, Vasile; Bele, Adrian; Vlad, Stelian; Vasiliu, Tudor; Cazacu, Maria; Vasiliu, Ana-Lavinia; Racles, Carmen

2017-10-01

Iron oxide nanoparticles were prepared using an alkaline precipitation method to tune the reaction time so as to afford ferrihydrite with spherical morphology or goethite nanorods. These two nanoparticle types, surface-treated with a surfactant (Pluronic L81), were each incorporated in 10, 20 and 30 wt% within a polydimethylsiloxane-α,ω-diol (Mn = 60 000 g mol-1). The mixtures were processed as films and crosslinked by condensation with tetraethoxysilane at room temperature. The aged films were investigated concerning filler distribution (by SEM coupled with an energy-dispersive x-ray spectroscopy module), mechanical (tensile strength, elongation and Young’s modulus), and dielectric properties (permittivity, loss, conductivity and strength). The results show that the fillers have a relatively homogeneous distribution within the matrix and, dependent on the filler nature and amount, generally manifest a mechanical reinforcing effect and act as dielectric permittivity and strength enhancers. In addition, it has been found that the crystalline nanoparticles induce a piezoelectric response, emphasized by piezoelectric force microscopy. The improved properties of the composites make them suitable for applications in mechanical/electrical energy conversion, as theoretical estimates showed.

Self-assembled Lyotropic Liquid Crystalline Phase Behavior of Monoolein-Capric Acid-Phospholipid Nanoparticulate Systems.

PubMed

Zhai, Jiali; Tran, Nhiem; Sarkar, Sampa; Fong, Celesta; Mulet, Xavier; Drummond, Calum J

2017-03-14

We report here the lyotropic liquid crystalline phase behavior of two lipid nanoparticulate systems containing mixtures of monoolein, capric acid, and saturated diacyl phosphatidylcholines dispersed by the Pluronic F127 block copolymer. Synchrotron small-angle X-ray scattering (SAXS) was used to screen the phase behavior of a library of lipid nanoparticles in a high-throughput manner. It was found that adding capric acid and phosphatidylcholines had opposing effects on the spontaneous membrane curvature of the monoolein lipid layer and hence the internal mesophase of the final nanoparticles. By varying the relative concentration of the three lipid components, we were able to establish a library of nanoparticles with a wide range of mesophases including at least the inverse bicontinuous primitive and double diamond cubic phases, the inverse hexagonal phase, the fluid lamellar phase, and possibly other phases. Furthermore, the in vitro cytotoxicity assay showed that the endogenous phospholipid-containing nanoparticles were less toxic to cultured cell lines compared to monoolein-based counterparts, improving the potential of the nonlamellar lipid nanoparticles for biomedical applications.

Novel sol-gel precursors for thin mesoporous eu(3+)-doped silica coatings as efficient luminescent materials.

PubMed

Feinle, Andrea; Lavoie-Cardinal, Flavie; Akbarzadeh, Johanna; Peterlik, Herwig; Adlung, Matthias; Wickleder, Claudia; Hüsing, Nicola

2012-10-09

Europium(III) ions containing mesoporous silica coatings have been prepared via a solvent evaporation-induced self-assembly (EISA) approach of different single-source precursors (SSPs) in the presence of Pluronic P123 as a structure-directing agent, using the spin-coating process. A deliberate tailoring of the chemical composition of the porous coatings with various Si:Eu ratios was achieved by processing mixtures of tetraethylorthosilicate (TEOS) and Eu(3+)-coordinated SSPs. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses demonstrate that the thin metal oxide-doped silica coatings consist of a porous network with a short-range order of the pore structure, even at high europium(III) loadings. Furthermore, luminescence properties were investigated at different temperatures and different degrees of Eu(3+) contents. The photoluminescence spectra clearly show characteristic emission peaks corresponding to the (5)D0 → (7)FJ (J = 0-5) transitions resulting in a red luminescence visible by the eyes, although the films have a very low thickness (150-200 nm).

Synthesis, characterization and photocatalytic performance of self-assembled mesoporous TiO₂ nanoparticles.

PubMed

Lin, Yuan-Chung; Liu, Shou-Heng; Syu, Han-Ren; Ho, Tsung-Han

2012-09-01

A facile synthesis route is reported for preparation of mesoporous TiO(2) nanoparticles (MT-x) through evaporation induced self-assembly by using Pluronic F127, titanium isopropoxide, and various amounts of ethanol as templating agents, titanium sources and solvents, respectively. A variety of different spectroscopic and analytical techniques, such as small- and large-angle powder X-ray diffraction (XRD), N(2) adsorption-desorption isotherms, transmission electron microscopy (TEM), Raman and Fourier transform infrared (FTIR) spectroscopies were used to characterize the physicochemical properties of various MT-x catalysts. Among the catalysts, MT-20 was found to have better mesostructures formed by the arrangement of anatase TiO(2) nanoparticles of ca. 17.3 nm with broad interparticle pore size distribution. Hydrogen generation from water splitting on MT-20 using visible light was enhanced by at least 8.7 times if compared with the conventional TiO(2) photocatalyst. The superior photocatalytic performances observed for the synthesized MT-20 may be attributed to the presence of unique nanostructures in the TiO(2) photocatalysts. Copyright © 2012 Elsevier B.V. All rights reserved.

Study and description of hydrogels and organogels as vehicles for cosmetic active ingredients.

PubMed

Morales, M E; Gallardo, V; Clarés, B; García, M B; Ruiz, M A

2009-01-01

Cellulite, a clinical syndrome mainly affecting women, involves specific changes in conjunctive dermic and subcutaneous tissue, leading to vascular and hypertrophic alterations in adipose tissues and the consequent alteration of tissue structure. This paper describes the design of hydrogels and pluronic-lecithin organogels elaborated as vehicles of Aloe vera (Aloe vera linné) and Hydrocotyle asiatica (Centella asiatica) for the treatment of cellulite. The objective of this work was to carry out a complete evaluation of the proposed formulae through the study of the organoleptic and rheological properties of the formulae. Our work revealed that, in appearance, hydrogels show better organoleptic characteristics than organogels. On the other hand, from a rheological point of view, both hydrogels and organogels display a plastic behavior. However, the main difference between the two is that the more complex internal structure of the organogel bestows it with more viscosity. Finally, in vitro tests with Franz-type diffusion cells revealed that the release of cosmetic active principle from the tested excipients was appropriate, both in terms of magnitude and velocity.

AFM-porosimetry: density and pore volume measurements of particulate materials.

PubMed

Sörensen, Malin H; Valle-Delgado, Juan J; Corkery, Robert W; Rutland, Mark W; Alberius, Peter C

2008-06-01

We introduced the novel technique of AFM-porosimetry and applied it to measure the total pore volume of porous particles with a spherical geometry. The methodology is based on using an atomic force microscope as a balance to measure masses of individual particles. Several particles within the same batch were measured, and by plotting particle mass versus particle volume, the bulk density of the sample can be extracted from the slope of the linear fit. The pore volume is then calculated from the densities of the bulk and matrix materials, respectively. In contrast to nitrogen sorption and mercury porosimetry, this method is capable of measuring the total pore volume regardless of pore size distribution and pore connectivity. In this study, three porous samples were investigated by AFM-porosimetry: one ordered mesoporous sample and two disordered foam structures. All samples were based on a matrix of amorphous silica templated by a block copolymer, Pluronic F127, swollen to various degrees with poly(propylene glycol). In addition, the density of silica spheres without a template was measured by two independent techniques: AFM and the Archimedes principle.

Intestinal Lymphatic Transport: an Overlooked Pathway for Understanding Absorption of Plant Secondary Compounds in Vertebrate Herbivores.

PubMed

Kohl, Kevin D; Dearing, M Denise

2017-03-01

Herbivores employ numerous strategies to reduce their exposure to toxic plant secondary chemicals (PSCs). However, the physiological mechanisms of PSC absorption have not been extensively explored. In particular, the absorption of PSCs via intestinal lymphatic absorption has been largely overlooked in herbivores, even though this pathway is well recognized for pharmaceutical uptake. Here, we investigated for the first time whether PSCs might be absorbed by lymphatic transport. We fed woodrats (Neotoma albigula) diets with increasing concentrations of terpene-rich juniper (Juniperus monosperma) either with or without a compound that blocks intestinal lymphatic absorption (Pluronic L-81). Woodrats consuming diets that contained the intestinal lymphatic absorption blocker exhibited increased food intakes and maintained higher body masses on juniper diets. Our study represents the first demonstration that PSCs may be absorbed by intestinal lymphatic absorption. This absorption pathway has numerous implications for the metabolism and distribution of PSCs in the systemic circulation, given that compounds absorbed via lymphatic transport bypass first-pass hepatic metabolism. The area of lymphatic transport of PSCs represents an understudied physiological pathway in plant-herbivore interactions.

Ultrafast photoinduced electron transfer in the micelle and the gel phase of a PEO-PPO-PEO triblock copolymer

NASA Astrophysics Data System (ADS)

Mandal, Ujjwal; Ghosh, Subhadip; Dey, Shantanu; Adhikari, Aniruddha; Bhattacharyya, Kankan

2008-04-01

Ultrafast photoinduced electron transfer (PET) from N,N-dimethylaniline (DMA) to coumarin dyes is studied in the micelle and the gel phase of a triblock copolymer, (PEO)20-(PPO)70-(PEO)20 (Pluronic P123) by picosecond and femtosecond emission spectroscopies. The rate of PET in a P123 micelle and gel is found to be nonexponential and faster than the slow components of solvation dynamics. In a P123 micelle and gel, PET occurs on multiple time scales ranging from a subpicosecond time scale to a few nanoseconds. In the gel phase, the highest rate constant (9.3×109M-1s-1) of ET for C152 is about two times higher than that (3.8×109M-1s-1) observed in micelle phase. The ultrafast components of electron transfer (ET) exhibits a bell shaped dependence with the free energy change which is similar to the Marcus inversion. Possible reasons for slower PET in P123 micelle compared to other micelles and relative to P123 gel are discussed.

Formulation of Poloxamers for Drug Delivery

PubMed Central

Bodratti, Andrew M.; Alexandridis, Paschalis

2018-01-01

Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective. PMID:29346330

Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

PubMed Central

Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

2012-01-01

Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles comprised of poly (ethylene oxide)-poly-[(R)-3-hydroxybutyrate]-poly (ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by non-invasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability was attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components. PMID:22118658

Self-Healing and Thermo-Responsive Dual-Crosslinked Alginate Hydrogels based on Supramolecular Inclusion Complexes

PubMed Central

Miao, Tianxin; Fenn, Spencer L.; Charron, Patrick N.; Oldinski, Rachael A.

2015-01-01

β-cyclodextrin (β-CD), with a lipophilic inner cavity and hydrophilic outer surface, interacts with a large variety of non-polar guest molecules to form non-covalent inclusion complexes. Conjugation of β-CD onto biomacromolecules can form physically-crosslinked hydrogel networks upon mixing with a guest molecule. Herein describes the development and characterization of self-healing, thermo-responsive hydrogels, based on host-guest inclusion complexes between alginate-graft-β-CD and Pluronic® F108 (poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol)). The mechanics, flow characteristics, and thermal response were contingent on the polymer concentrations, and the host-guest molar ratio. Transient and reversible physical crosslinking between host and guest polymers governed self-assembly, allowing flow under shear stress, and facilitating complete recovery of the material properties within a few seconds of unloading. The mechanical properties of the dual-crosslinked, multi-stimuli responsive hydrogels were tuned as high as 30 kPa at body temperature, and are advantageous for biomedical applications such as drug delivery and cell transplantation. PMID:26509214

Highly bacterial resistant silver nanoparticles: synthesis and antibacterial activities

NASA Astrophysics Data System (ADS)

Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Mehta, R. V.; Upadhyay, R. V.

2010-06-01

In this article, we describe a simple one-pot rapid synthesis route to produce uniform silver nanoparticles by thermal reduction of AgNO3 using oleylamine as reducing and capping agent. To enhance the dispersal ability of as-synthesized hydrophobic silver nanoparticles in water, while maintaining their unique properties, a facile phase transfer mechanism has been developed using biocompatible block co-polymer pluronic F-127. Formation of silver nanoparticles is confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and UV-vis spectroscopy. Hydrodynamic size and its distribution are obtained from dynamic light scattering (DLS). Hydrodynamic size and size distribution of as-synthesized and phase transferred silver nanoparticles are 8.2 ± 1.5 nm (σ = 18.3%) and 31.1 ± 4.5 nm (σ = 14.5%), respectively. Antimicrobial activities of hydrophilic silver nanoparticles is tested against two Gram positive ( Bacillus megaterium and Staphylococcus aureus), and three Gram negative ( Escherichia coli, Proteus vulgaris and Shigella sonnei) bacteria. Minimum inhibitory concentration (MIC) values obtained in the present study for the tested microorganisms are found much better than those reported for commercially available antibacterial agents.

Washing-resistant surfactant coated surface is able to inhibit pathogenic bacteria adhesion

NASA Astrophysics Data System (ADS)

Treter, Janine; Bonatto, Fernando; Krug, Cristiano; Soares, Gabriel Vieira; Baumvol, Israel Jacob Rabin; Macedo, Alexandre José

2014-06-01

Surface-active substances, which are able to organize themselves spontaneously on surfaces, triggering changes in the nature of the solid-liquid interface, are likely to influence microorganism adhesion and biofilm formation. Therefore, this study aimed to evaluate chemical non-ionic surfactants activity against pathogenic microbial biofilms and to cover biomaterial surfaces in order to obtain an anti-infective surface. After testing 11 different surfactants, Pluronic F127 was selected for further studies due to its non-biocidal properties and capability to inhibit up to 90% of biofilm formation of Gram-positive pathogen and its clinical isolates. The coating technique using direct impregnation on the surface showed important antibiofilm formation characteristics, even after extensive washes. Surface roughness and bacterial surface polarity does not influence the adhesion of Staphylococcus epidermidis, however, the material coated surface became extremely hydrophilic. The phenotype of S. epidermidis does not seem to have been affected by the contact with surfactant, reinforcing the evidence that a physical phenomenon is responsible for the activity. This paper presents a simple method of surface coating employing a synthetic surfactant to prevent S. epidermidis biofilm formation.

Synthesis of Mesoporous α-Fe2O3 Nanoparticles by Non-ionic Soft Template and Their Applications to Heavy Oil Upgrading

NASA Astrophysics Data System (ADS)

Park, Chulwoo; Jung, Jinhwan; Lee, Chul Wee; Cho, Joungmo

2016-12-01

This paper reports the synthetic route of 3-D network shape α-Fe2O3 from aqueous solutions of iron precursor using a non-ionic polymeric soft-template, Pluronic P123. During the synthesis of α-Fe2O3, particle sizes, crystal phases and morphologies were significantly influenced by pH, concentrations of precursor and template. The unique shape of worm-like hematite was obtained only when a starting solution was prepared by a weakly basic pH condition and a very specific composition of constituents. The synthesized nanocrystal at this condition had a narrow pore size distribution and high surface area compared to the bulk α-Fe2O3 or the one synthesized from lower pH conditions. The hydrocracking performance was tested over the synthesized iron oxide catalysts with different morphologies. The worm-like shape of iron oxide showed a superior performance, including overall yield of liquid fuel product and coke formation, over the hydrocracking of heavy petroleum oil.

Synthesis of Mesoporous α-Fe2O3 Nanoparticles by Non-ionic Soft Template and Their Applications to Heavy Oil Upgrading

PubMed Central

Park, Chulwoo; Jung, Jinhwan; Lee, Chul Wee; Cho, Joungmo

2016-01-01

This paper reports the synthetic route of 3-D network shape α-Fe2O3 from aqueous solutions of iron precursor using a non-ionic polymeric soft-template, Pluronic P123. During the synthesis of α-Fe2O3, particle sizes, crystal phases and morphologies were significantly influenced by pH, concentrations of precursor and template. The unique shape of worm-like hematite was obtained only when a starting solution was prepared by a weakly basic pH condition and a very specific composition of constituents. The synthesized nanocrystal at this condition had a narrow pore size distribution and high surface area compared to the bulk α-Fe2O3 or the one synthesized from lower pH conditions. The hydrocracking performance was tested over the synthesized iron oxide catalysts with different morphologies. The worm-like shape of iron oxide showed a superior performance, including overall yield of liquid fuel product and coke formation, over the hydrocracking of heavy petroleum oil. PMID:27966663

Synthesis of Mesoporous α-Fe2O3 Nanoparticles by Non-ionic Soft Template and Their Applications to Heavy Oil Upgrading.

PubMed

Park, Chulwoo; Jung, Jinhwan; Lee, Chul Wee; Cho, Joungmo

2016-12-14

This paper reports the synthetic route of 3-D network shape α-Fe 2 O 3 from aqueous solutions of iron precursor using a non-ionic polymeric soft-template, Pluronic P123. During the synthesis of α-Fe 2 O 3 , particle sizes, crystal phases and morphologies were significantly influenced by pH, concentrations of precursor and template. The unique shape of worm-like hematite was obtained only when a starting solution was prepared by a weakly basic pH condition and a very specific composition of constituents. The synthesized nanocrystal at this condition had a narrow pore size distribution and high surface area compared to the bulk α-Fe 2 O 3 or the one synthesized from lower pH conditions. The hydrocracking performance was tested over the synthesized iron oxide catalysts with different morphologies. The worm-like shape of iron oxide showed a superior performance, including overall yield of liquid fuel product and coke formation, over the hydrocracking of heavy petroleum oil.

Effect of squalane on mebendazole-loaded Compritol® nanoparticles.

PubMed

Graves, Richard A; Ledet, Grace A; Nation, Cedric A; Pramar, Yashoda V; Bostanian, Levon A; Mandal, Tarun K

2015-01-01

The objective of this study is to develop nanostructured lipid formulations of Compritol for the delivery of mebendazole. The formulations were prepared with Compritol 888 ATO, squalane, and Pluronic F68. Nine batches with different amounts of modifier, squalane, and drug were prepared. The formulations were characterized by evaluating particle size, morphology, and zeta potential. The thermal properties of the formulations were analyzed by differential scanning calorimetry (DSC). The encapsulation efficiency of each formulation and the drug release rates from each formulation were quantified by UPLC. The particles were spherical and had median particle sizes between 300 and 600 nm (50th percentile). A linear relationship was observed between Compritol/squalane composition and the melting point of the mixture. The DSC scans of the formulations revealed some recrystallization of the drug from the formulations, and the amount of recrystallization correlated with the amount of squalane in the formulation. Approximately, 70% efficiency of encapsulation was observed in the formulations with 30% (w/w) squalane, and these formulations also had faster dissolution rates compared to the other formulations. Overall, the formulations with 30% squalane are the preferred formulation for future testing.

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

PubMed

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilde, E.W.; Radway, J.C.; Hazen, T.C.

The immobilization of TCE-degrading bacterium Burkholderia cepacia was evaluated using hydrophilic polyurethane foam. The influence of several foam formulation parameters upon cell retention was examined. Surfactant type was a major determinant of retention, with a lecithin- based compound retaining more cells than pluronic or silicone based surfactants. Excessive amounts of surfactant led to increased washout of bacteria. Increasing the biomass concentration from 4.8% to 10.5% caused fewer cells to be washed out. Embedding at reduced temperature did not significantly affect retention, while the use of a silane binding agent gave inconsistent results. The optimal formulation retained all but 0.2% ofmore » total embedded cells during passage of 2 liters of water through columns containing 2 g of foam. All foam formulations tested reduced the culturability of embedded cells by several orders of magnitude. However, O{sub 2} and CO{sub 2} evolution rates of embedded cells were never less than 50% of unembedded cells. Nutrient amendments stimulated an increase in cell volume and ribosomal activity as indicated by hybridization studies using fluorescently labeled ribosomal probes. these results indicated that, although immobilized cells were nonculturable, they were metabolically active and thus could be used for biodegradation of toxic compounds.« less

Influence of metal electrodes on the response of humidity sensors coated with mesoporous silica

NASA Astrophysics Data System (ADS)

Bearzotti, Andrea

2008-01-01

Interesting effects of different metal electrodes on the behaviour of mesoporous based humidity sensors have been observed and studied by chemical characterization and electric measurements. The devices were prepared on passivated silicon slices utilizing an interdigitated structure as contacts. For comparison, the response of a device implemented on an alumina substrate has been reported. A block copolymer Pluronic F-127 has been used as the organic template and has been partially removed from the films by thermal calcination. A thin film mesoporous membrane has been deposited by dip-coating on the substrates in a sol-gel solution containing non-ionic block copolymers. Silica mesostructured films have been produced using an evaporation induced self-assembling process. The films were calcined at 150 °C to obtain the best performances in terms of stability, hysteresis and reproducibility of the response. The performance of the sensor has been found to be dependent on the film preparation method, the used electrodes and the substrate when exposed to different contents of relative humidity. Electrical characterization was performed under vacuum and dark conditions to investigate the properties of the materials in the absence of interfering chemicals, while the sensory properties were obtained in a controlled environment.

Interaction between curcumin and human serum albumin in the presence of excipients and the effect of binding on curcumin photostability.

PubMed

Vukićević, Milica; Tønnesen, Hanne Hjorth

2016-01-01

Curcumin (Cur) is known to bind to human serum albumin (HSA) which may lead to a reduced phototoxic effect of the compound in the presence of serum or saliva. The influence of excipients on the Cur-HSA binding was studied by HSA florescence quenching and Cur absorption and emission spectroscopy in the presence and absence of the selected excipients. Photostabilty of Cur in the presence of HSA was evaluated, as well as the effect of excipients on HSA bound Cur photodegradation. Cyclodextrins (CDs) (2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin) and polymers (polyethylene glycol 400, PEG 400 and Pluronic F-127, PF-127) were selected for the study. CDs and PF-127 seem to decrease Cur binding to HSA, probably through competitive binding. Cur was still bound to HSA in polyethylene glycol (PEG) solutions at the highest investigated concentration (5% w/v). However, high PEG concentration appears to have effect on the protein conformation, as shown by the fluorescence quenching study. Low Cur photostability in the presence of HSA could be improved by the addition of hydroxylpropyl-γ-cyclodextrin (HPγCD) to the samples, whereas PEG and PF-127 showed no effect.

Bioerodible System for Sequential Release of Multiple Drugs

PubMed Central

Sundararaj, Sharath C.; Thomas, Mark V.; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

Facile synthesis of AIE-active amphiphilic polymers: Self-assembly and biological imaging applications.

PubMed

Long, Zi; Liu, Meiying; Wang, Ke; Deng, Fengjie; Xu, Dazhuang; Liu, Liangji; Wan, Yiqun; Zhang, Xiaoyong; Wei, Yen

2016-09-01

In this work, we reported a rather facile method for fabrication of ultrabright, well dispersible and biocompatible fluorescent organic nanoparticles (FONs) with aggregation-induced emission (AIE) properties through combination of esterification and ring-opening reaction. The hydroxyl groups of Pluronic F127 was first reacted with the chloride of trimellitic anhydride chloride (TMAC), and its anhydride groups were further reacted with the amino groups of amino-terminated AIE dye (PhNH2) through ring-opening reaction. The optical properties, biocompatibility as well as cell uptake behavior of these obtained AIE-active nanoparticles (F127-TMAC-PhNH2 FONs) were examined by a series of characterization techniques and assays. We demonstrated that uniform organic nanoparticles with high water dispersibility, strong luminescence and desirable biocompatibility can be facilely obtained, which are promising for biological imaging applications. More importantly, a number of carboxyl groups were introduced into these AIE-active nanoparticles, which can be further utilized for further conjugation reaction and carrying anticancer drugs such as cisplatin. Therefore, the strategy of described in this work should be a simple and useful route for fabrication of multifunctional AIE-active luminescent nanotheranostic systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Lyotropic liquid crystalline phase behaviour in amphiphile-protic ionic liquid systems.

PubMed

Chen, Zhengfei; Greaves, Tamar L; Fong, Celesta; Caruso, Rachel A; Drummond, Calum J

2012-03-21

Approximate partial phase diagrams for nine amphiphile-protic ionic liquid (PIL) systems have been determined by synchrotron source small angle X-ray scattering, differential scanning calorimetry and cross polarised optical microscopy. The binary phase diagrams of some common cationic (hexadecyltrimethyl ammonium chloride, CTAC, and hexadecylpyridinium bromide, HDPB) and nonionic (polyoxyethylene (10) oleyl ether, Brij 97, and Pluronic block copolymer, P123) amphiphiles with the PILs, ethylammonium nitrate (EAN), ethanolammonium nitrate (EOAN) and diethanolammonium formate (DEOAF), have been studied. The phase diagrams were constructed for concentrations from 10 wt% to 80 wt% amphiphile, in the temperature range 25 °C to >100 °C. Lyotropic liquid crystalline phases (hexagonal, cubic and lamellar) were formed at high surfactant concentrations (typically >50 wt%), whereas at <40 wt%, only micelles or polydisperse crystals were present. With the exception of Brij 97, the thermal stability of the phases formed by these surfactants persisted to temperatures above 100 °C. The phase behaviour of amphiphile-PIL systems was interpreted by considering the PIL cohesive energy, liquid nanoscale order, polarity and ionicity. For comparison the phase behaviour of the four amphiphiles was also studied in water.

Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

PubMed

Tian, Ye; Mao, Shirui

2012-06-01

Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.

PubMed

Chang, Chia-Yu; Chen, Sheng-Mei; Lu, Huai-En; Lai, Syu-Ming; Lai, Ping-Shan; Shen, Po-Wen; Chen, Pei-Ying; Shen, Ching-I; Harn, Horng-Jyh; Lin, Shinn-Zong; Hwang, Shiaw-Min; Su, Hong-Lin

2015-03-04

Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.

Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.

PubMed

Oh, Keun Sang; Kim, Kyungim; Yoon, Byeong Deok; Lee, Hye Jin; Park, Dal Yong; Kim, Eun-Yeong; Lee, Kiho; Seo, Jae Hong; Yuk, Soon Hong

2016-01-01

A mixture of docetaxel (DTX) and Solutol(®) HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects.

Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

PubMed Central

Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

2013-01-01

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma. PMID:23626707

Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

PubMed

Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

2013-01-01

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

Structural and Luminescence Properties of Lu2O3:Eu3+ F127 Tri-Block Copolymer Modified Thin Films Prepared by Sol-Gel Method

PubMed Central

de Jesus Morales Ramírez, Angel; Hernández, Margarita García; Murillo, Antonieta García; de Jesús Carrillo Romo, Felipe; Palmerin, Joel Moreno; Velazquez, Dulce Yolotzin Medina; Jota, María Luz Carrera

2013-01-01

Lu2O3:Eu3+ transparent, high density, and optical quality thin films were prepared using the sol-gel dip-coating technique, starting with lutetium and europium nitrates as precursors and followed by hydrolysis in an ethanol-ethylene glycol solution. Acetic acid and acetylacetonate were incorporated in order to adjust pH and as a sol stabilizer. In order to increment the thickness of the films and orient the structure, F127 Pluronic acid was incorporated during the sol formation. Structural, morphological, and optical properties of the films were investigated for different F127/Lu molar ratios (0–5) in order to obtain high optical quality films with enhanced thickness compared with the traditional method. X-ray diffraction (XRD) shows that the films present a highly oriented cubic structure <111> beyond 1073 K for a 3-layer film, on silica glass substrates. The thickness, density, porosity, and refractive index evolution of the films were investigated by means of m-lines microscopy along with the morphology by scanning electron microscope (SEM) and luminescent properties. PMID:28809336

Fluorination of phthalocyanine substituents: Improved photoproperties and enhanced photodynamic efficacy after optimal micellar formulations.

PubMed

Pucelik, Barbara; Gürol, Ilke; Ahsen, Vefa; Dumoulin, Fabienne; Dąbrowski, Janusz M

2016-11-29

A fluorinated phthalocyanine and its non-fluorinated analogue were selected to evaluate the potential enhancement of fluorination on photophysical, photochemical and redox properties as well as on biological activity in cellular and animal models. Due to the pharmacological relevance, the affinity of these phthalocyanines towards biological membranes (logP ow ) as well as their primary interaction with human serum albumin (HSA) or low-density lipoprotein (LDL) were determined. Water-dispersible drug formulation of phthalocyanines via Pluronic ® -based triblock copolymer micelles was prepared to avoid self-aggregation effects and to improve their delivery. The obtained results demonstrate that phthalocyanines incorporation into tunable-polymeric micelles significantly enhanced their cellular uptake and their photocytotoxicity. The improved biodistribution and photodynamic efficacy of the phthalocyanines-triblock copolymer conjugates was also confirmed in vivo in CT26 bearing BALB/c mice. PDT with both compounds led to tumor growth inhibition in all treated animals. Fluorinated phthalocyanine 2 turned out to be the most effective anticancer agent as the tumors of 20% of mice treated regressed completely and did not appear for over one year after treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mesoporous titanosilicates with high loading of titanium synthesized in mild acidic buffer solution.

PubMed

Tang, Jianting; Liu, Jian; Yang, Jie; Feng, Zhaochi; Fan, Fengtao; Yang, Qihua

2009-07-15

Mesoporous titanosilicates with high titanium content were synthesized under mild acidic conditions (pH=4.4, HAc-NaAc buffer solution) by co-condensation of acetylacetone-modified titanium isopropoxide (Ti(OBu(n))(3) (acac)) and mixture of sodium silicate with tetramethoxysilane (TMOS) or tetraethoxysilane (TEOS) or tetrakis(2-hydroxyethyl)orthosilicate (EGMS), using block copolymer Pluronic P123 as template. The combined results of XRD, N(2) sorption and TEM show that the highly regular structure of the mesoporous titanosilicates can still be obtained when Ti/Si molar ratio in the final product is as high as 0.059. The results of UV-vis diffuse reflectance spectra and UV resonance Raman spectra show that the framework titanium species are predominant in the mesoporous titanosilicates when Ti/Si molar ratio in the final product is less than 0.042. The mixture of sodium silicate and EGMS was proved to be the best silicon source for the synthesis of titanosilicates with ordered mesostructure and high titanium content. The efficiency of this synthetic method may be attributed to the mild acidic medium as well as the modified hydrolysis-condensation rate and hydrophility of the precursors.

Preparation of ordered mesoporous alumina-doped titania films with high thermal stability and their application to high-speed passive-matrix electrochromic displays.

PubMed

Jiang, Xiangfen; Bastakoti, Bishnu Prasad; Weng, Wu; Higuchi, Tetsuya; Oveisi, Hamid; Suzuki, Norihiro; Chen, Wei-Jung; Huang, Yu-Tzu; Yamauchi, Yusuke

2013-08-12

Ordered mesoporous alumina-doped titania thin films with anatase crystalline structure were prepared by using triblock copolymer Pluronic P123 as structure-directing agent. Uniform Al doping was realized by using aluminum isopropoxide as a dopant source which can be hydrolyzed together with titanium tetraisopropoxide. Aluminum doping into the titania framework can prevent rapid crystallization to the anatase phase, thereby drastically increasing thermal stability. With increasing Al content, the crystallization temperatures tend to increase gradually. Even when the Al content doped into the framework was increased to 15 mol %, a well-ordered mesoporous structure was obtained, and the mesostructural ordering was still maintained after calcination at 550 °C. During the calcination process, large uniaxial shrinkage occurred along the direction perpendicular to the substrate with retention of the horizontal mesoscale periodicity, whereby vertically oriented nanopillars were formed in the film. The resulting vertical porosity was successfully exploited to fabricate a high-speed and high-quality passive-matrix electrochromic display by using a leuco dye. The vertical nanospace in the films can effectively prevent drifting of the leuco dye. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rare-earth metal oxide doped transparent mesoporous silica plates under non-aqueous condition as a potential UV sensor.

PubMed

Lee, Sang-Joon; Park, Sung Soo; Lee, Sang Hyun; Hong, Sang-Hyun; Ha, Chang-Sik

2013-11-01

Transparent mesoporous silica plates doped with rare-earth metal oxide were prepared using solvent-evaporation method based on the self-organization between structure-directing agent and silicate in a non-aqueous solvent. A triblock copolymer, Pluronic (F127 or P123), was used as the structure-directing agent, while tetraethyl orthosilicate (TEOS) was used as a silica source. The pore diameter and the surface area of the mesoporous silica plate prepared with the optimized conditions were ca 40 A and 600 m2 g(-1), respectively, for both structure-directing agent. Rare-earth metal oxides (Eu, Tb, Tm oxide) in mesochannel were formed via one-step synthetic route based on the preparation method of a silica plate. Optical properties of rare-earth metal oxide-doped mesoporous silica plates were investigated by UV irradiation and photoluminescence (PL) spectroscopy. Under the exitation wavelength of 254 nm, the doped mesoporous silica plates emitted red, green and blue for Eu, Tb and Tm oxides, respectively. Rare-earth metal oxide-doped mesoporous silica plates showed enhanced PL intensity compared to that of the bulk rare-earth metal oxide.

Synthesis of 5-hydroxymethylfurural from carbohydrates using large-pore mesoporous tin phosphate.

PubMed

Dutta, Arghya; Gupta, Dinesh; Patra, Astam K; Saha, Basudeb; Bhaumik, Asim

2014-03-01

A large-pore mesoporous tin phosphate (LPSnP-1) material has been synthesized hydrothermally by using Pluronic P123 as the structure-directing agent. The material is composed of aggregated nanoparticles of 10-15 nm in diameter and has a BET surface area of 216 m(2)  g(-1) with an average pore diameter of 10.4 nm. This pore diameter is twice as large as that of mesoporous tin phosphate materials synthesized through the surfactant-templating pathways reported previously. LPSnP-1 shows excellent catalytic activity for the conversion of fructose, glucose, sucrose, cellobiose, and cellulose to 5-hydroxymethylfurfural (HMF) in a water/methyl isobutyl ketone biphasic solvent to give maximum yields of HMF of 77, 50, 51, 39, and 32 mol %, respectively, under microwave-assisted heating at 423 K. Under comparable reaction conditions, LPSnP-1 gives 12 % more HMF yield than a small-pore mesoporous tin phosphate catalyst that has an identical framework composition. This confirms the beneficial role of large mesopores and nanoscale particle morphology in catalytic reactions that involve bulky natural carbohydrate molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control of Partial Coalescence of Self-Assembled Metal Nano-Particles across Lyotropic Liquid Crystals Templates towards Long Range Meso-Porous Metal Frameworks Design

PubMed Central

Dumée, Ludovic F.; Lemoine, Jean-Baptiste; Ancel, Alice; Hameed, Nishar; He, Li; Kong, Lingxue

2015-01-01

The formation of purely metallic meso-porous metal thin films by partial interface coalescence of self-assembled metal nano-particles across aqueous solutions of Pluronics triblock lyotropic liquid crystals is demonstrated for the first time. Small angle X-ray scattering was used to study the influence of the thin film composition and processing conditions on the ordered structures. The structural characteristics of the meso-structures formed demonstrated to primarily rely on the lyotropic liquid crystal properties while the nature of the metal nano-particles used as well as the their diameters were found to affect the ordered structure formation. The impact of the annealing temperature on the nano-particle coalescence and efficiency at removing the templating lyotropic liquid crystals was also analysed. It is demonstrated that the lyotropic liquid crystal is rendered slightly less thermally stable, upon mixing with metal nano-particles and that low annealing temperatures are sufficient to form purely metallic frameworks with average pore size distributions smaller than 500 nm and porosity around 45% with potential application in sensing, catalysis, nanoscale heat exchange, and molecular separation. PMID:28347094

Development and Application of a High-Performance Liquid Chromatography Stability-Indicating Assay for Beyond-Use Date Determination of Compounded Topical Gels Containing Multiple Active Drugs.

PubMed

Gorman, Gregory; Sokom, Simara; Coward, Lori; Arnold, John J

2017-01-01

Topical gels compounded by pharmacists are important clinical tools for the management of pain. Nevertheless, there is often a dearth of information about the chemical stability of drugs included in these topical formulations, complicating the assignment of beyond-use dating. The purpose of this study was to develop a high-performance liquid chromatography photodiode array-based stability-indicating assay that could simultaneously resolve six drugs (amitriptyline, baclofen, clonidine, gabapentin, ketoprofen, lidocaine) commonly included in topical gels for pain management and their potential degradation products. Furthermore, this method was applied to the determination of beyond-use dating of combinations of these drugs prepared in commonly utilized bases (Lipobase, Lipoderm, Pluronic organogel). Gabapentin was determined to be the least stable component in all formulations tested. Measured stability ranged between 7 to 49 days depending on the base and other active drugs present in the formulation. In the absence of gabapentin, baclofen was the next least stable component, lasting for 120 days, regardless of the type of formulating base used. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

High performance sulfur, nitrogen and carbon doped mesoporous anatase-brookite TiO₂ photocatalyst for the removal of microcystin-LR under visible light irradiation.

PubMed

El-Sheikh, Said M; Zhang, Geshan; El-Hosainy, Hamza M; Ismail, Adel A; O'Shea, Kevin E; Falaras, Polycarpos; Kontos, Athanassios G; Dionysiou, Dionysios D

2014-09-15

Carbon, nitrogen and sulfur (C, N and S) doped mesoporous anatase-brookite nano-heterojunction titania photocatalysts have been synthesized through a simple sol-gel method in the presence of triblock copolymer Pluronic P123. XRD and Raman spectra revealed the formation of anatase and brookite mixed phases. XPS spectra indicated the presence of C, N and S dopants. The TEM images demonstrated the formation of almost monodisperse titania nanoparticles with particle sizes of approximately 10nm. N2 isotherm measurements confirmed that both doped and undoped titania anatase-brookite materials have mesoporous structure. The photocatalytic degradation of the cyanotoxin microcystin-LR (MC-LR) has been investigated using these novel nanomaterials under visible light illumination. The photocatalytic efficiency of the mesoporous titania anatase-brookite photocatalyst dramatically increased with the addition of the C, N and S non-metal, achieving complete degradation (∼ 100 %) of MC-LR. The results demonstrate the advantages of the synthetic approach and the great potential of the visible light activated C, N, and S doped titania photocatalysts for the treatment of organic micropollutants in contaminated waters under visible light. Copyright © 2014 Elsevier B.V. All rights reserved.

Cubic liquid crystalline nanoparticles: optimization and evaluation for ocular delivery of tropicamide.

PubMed

Verma, Purnima; Ahuja, Munish

2016-10-01

The purpose of this study was to investigate the potential of cubic liquid crystalline nanoparticles for ocular delivery of tropicamide. Ultrasound-assisted fragmentation of cubic liquid crystalline bulk phases resulted in cubic liquid crystalline nanoparticles employing Pluronic F127 as dispersant. The effects of process variables such as sonication time, sonication amplitude, sonication depth, and pre-mixing time on particle size and polydispersity index was investigated using central composite design. The morphology of tropicamide-loaded nanoparticles was found to be nearly cubical in shape by transmission electron microscopy observation. Further, small angle X-ray scattering experiment confirmed the presence of D and P phase cubic structures in coexistence. The optimized tropicamide-loaded cubic nanoparticles showed in vitro corneal permeation of tropicamide across isolated porcine cornea comparable to its commercial preparation, Tropicacyl®. Ocular tolerance was evaluated by Hen's egg-chorioallantoic membrane test and histological studies. The results of in vivo mydriatic response study demonstrated a remarkably higher area under mydriatic response curve (AUC 0→1440 min ) values of cubic nanoparticles over Tropicacyl® indicating better therapeutic value of cubic nanoparticles. Furthermore, tropicamide-loaded cubic nanoparticles exhibited prolonged mydriatic effect on rabbits as compared to commercial conventional aqueous ophthalmic solution.

Preparation of solid lipid nanoparticles from W/O/W emulsions: preliminary studies on insulin encapsulation.

PubMed

Gallarate, Marina; Trotta, Michele; Battaglia, Luigi; Chirio, Daniela

2009-08-01

A method to produce solid lipid nanoparticles (SLN) from W/O/W multiple emulsions was developed applying the solvent-in-water emulsion-diffusion technique. Insulin was chosen as hydrophilic peptide drug to be dissolved in the acidic inner aqueous phase of multiple emulsions and to be consequently carried in SLN. Several partially water-miscible solvents with low toxicity were screened in order to optimize emulsions and SLN composition, after assessing that insulin did not undergo any chemical modification in the presence of the different solvents and under the production process conditions. SLN of spherical shape and with mean diameters in the 600-1200 nm range were obtained by simple water dilution of the W/O/W emulsion. Best results, in terms of SLN mean diameter and encapsulation efficiencies, were obtained using glyceryl monostearate as lipid matrix, butyl lactate as a solvent, and soy lecithin and Pluronic F68 as surfactants. Encapsulation efficiencies up to 40% of the loaded amount were obtained, owing to the actual multiplicity of the system; the use of multiple emulsion-derived SLN can be considered a useful strategy to encapsulate a hydrophilic drug in a lipid matrix.

Poloxamer surface modified trimethyl chitosan nanoparticles for the effective delivery of methotrexate in osteosarcoma.

PubMed

Li, Shenglong; Xiong, Yuyuan; Zhang, Xiaojing

2017-06-01

The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited a superior apoptosis effect with bright chromatin condensation and nuclear fragmentation was observed and showed remarkably higher apoptosis (∼48%) compared to that of free drug. The results of this investigation clearly demonstrate that the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential as a drug carrier in cancer chemotherapy. The present research work offers immense scope for further exploitation of poloxamer-modified trimethyl chitosan (TMC) in future for the development of nanoparticulate drug delivery system for cancer chemotherapy. Copyright © 2017. Published by Elsevier Masson SAS.

Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy.

PubMed

El-Sherbiny, I M; Smyth, H D C

2010-01-01

In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic® F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ∼10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery.

Cobalt ion-coordinated self-assembly synthesis of nitrogen-doped ordered mesoporous carbon nanosheets for efficiently catalyzing oxygen reduction.

PubMed

Wang, Haitao; Wang, Wei; Asif, Muhammad; Yu, Yang; Wang, Zhengyun; Wang, Junlei; Liu, Hongfang; Xiao, Junwu

2017-10-19

The design and synthesis of a promising porous carbon-based electrocatalyst with an ordered and uninterrupted porous structure for oxygen reduction reaction (ORR) is still a significant challenge. Herein, an efficient catalyst based on cobalt-embedded nitrogen-doped ordered mesoporous carbon nanosheets (Co/N-OMCNS) is successfully prepared through a two-step procedure (cobalt ion-coordinated self-assembly and carbonization process) using 3-aminophenol as a nitrogen source, cobalt acetate as a cobalt source and Pluronic F127 as a mesoporous template. This work indicates that the formation of a two dimensional nanosheet structure is directly related to the extent of the cobalt ion coordination interaction. Moreover, the critical roles of pyrolysis temperature in nitrogen doping and ORR catalytic activity are also investigated. Benefiting from the high surface area and graphitic degree, high contents of graphitic N and pyridinic N, ordered interconnected mesoporous carbon framework, as well as synergetic interaction between the cobalt nanoparticles and protective nitrogen doped graphitic carbon layer, the resultant optimal catalyst Co/N-OMCNS-800 (pyrolyzed at 800 °C) exhibits comparable ORR catalytic activity to Pt/C, superior tolerance to methanol crossover and stability.

Perivascular Delivery of Notch 1 siRNA Inhibits Injury-Induced Arterial Remodeling

PubMed Central

Redmond, Eileen M.; Liu, Weimin; Hamm, Katie; Hatch, Ekaterina; Cahill, Paul A.; Morrow, David

2014-01-01

Objectives To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling. Methods and Results Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown. Conclusion These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA. PMID:24416200

Evaluation of DNA damage and cytotoxicity of polyurethane-based nano- and microparticles as promising biomaterials for drug delivery systems

NASA Astrophysics Data System (ADS)

Caon, Thiago; Zanetti-Ramos, Betina Giehl; Lemos-Senna, Elenara; Cloutet, Eric; Cramail, Henri; Borsali, Redouane; Soldi, Valdir; Simões, Cláudia Maria Oliveira

2010-06-01

The in vitro cytotoxicity and DNA damage evaluation of biodegradable polyurethane-based micro- and nanoparticles were carried out on animal fibroblasts. For cytotoxicity measurement and primary DNA damage evaluation, MTT and Comet assays were used, respectively. Different formulations were tested to evaluate the influence of chemical composition and physicochemical characteristics of particles on cell toxicity. No inhibition of cells growth surrounding the polyurethane particles was observed. On the other hand, a decrease of cell viability was verified when the anionic surfactant sodium dodecyl sulfate (SDS) was used as droplets stabilizer of monomeric phase. Polyurethane nanoparticles stabilized with Tween 80 and Pluronic F68 caused minor cytotoxic effects. These results indicated that the surface charge plays an important role on cytotoxicity. Particles synthesized from MDI displayed a higher cytotoxicity than those synthesized from IPDI. Size and physicochemical properties of the particles may explain the higher degree of DNA damage produced by two tested formulations. In this way, a rational choice of particles' constituents based on their cytotoxicity and genotoxicity could be very useful for conceiving biomaterials to be used as drug delivering systems.

Thermo-reversible morphology and conductivity of a conjugated polymer network embedded in polymeric self-assembly

NASA Astrophysics Data System (ADS)

Han, Youngkyu; Carrillo, Jan-Michael Y.; Zhang, Zhe; Li, Yunchao; Hong, Kunlun; Sumpter, Bobby G.; Ohl, Michael; Paranthaman, Mariappan Parans; Smith, Gregory S.; Do, Changwoo

Self-assembly of block copolymers provides opportunities to create nano hybrid materials, utilizing self-assembled micro-domains with a variety of morphology and periodic architectures as templates for functional nano-fillers. Here we report new progress towards the fabrication of a thermally responsive conducting polymer self-assembly made from a water-soluble poly(thiophene) derivative with short PEO side chains and Pluronic L62 solution in water. The structural and electrical properties of conjugated polymer-embedded nanostructures were investigated by combining SANS, SAXS, CGMD simulations, and impedance spectroscopy. The L62 solution template organizes the conjugated polymers by stably incorporating them into the hydrophilic domains thus inhibiting aggregation. The changing morphology of L62 during the micellar-to-lamellar phase transition defines the embedded conjugated polymer network. The conductivity is strongly coupled to the structural change of the templating L62 phase and exhibits thermally reversible behavior with no signs of quenching of the conductivity at high temperature. The research was sponsored by the Scientific User Facilities Division, Office of BES, U.S. DOE and Laboratory Directed Research and Development Program of ORNL, managed by UT-Battelle, LLC.

Synthesis of porous carbon/silica nanostructured microfiber with ultrahigh surface area

NASA Astrophysics Data System (ADS)

Zhou, Dan; Dong, Yan; Cui, Liru; Lin, Huiming; Qu, Fengyu

2014-12-01

Carbon/silica-nanostructured microfibers were synthesized via electrospinning method using phenol-formaldehyde resin and tetraethyl orthosilicate as carbon and silica precursor with triblock copolymer Pluronic P123 as soft template. The prepared samples show uniform microfiber structure with 1 μm in diameter and dozens of microns in length. Additionally, the mesopores in the material is about 2-6 nm. When the silica component was removed by HF, the porous carbon microfibers (PCMFs) were obtained. In addition, after the carbon/silica composites were calcined in air, the porous silica microfibers (PSiMFs) were obtained, revealing the converse porous nanostructure as PCMFs. It is a simple way to prepare PCMFs and PSiMFs with silica and carbon as the template to each other. Additionally, PCMFs possess an ultrahigh specific surface area (2,092 m2 g-1) and large pore volume. The electrochemical performance of the prepared PCMF material was investigated in 6.0 M KOH electrolyte. The PCMF electrode exhibits a high specific capacitance (252 F g-1 at 0.5 A g-1). Then, superior cycling stability (97 % retention after 4,000 cycles) mainly is due to its unique nanostructure.

Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer

PubMed Central

Fan, Rangrang; Tong, Aiping; Li, Xiaoling; Gao, Xiang; Mei, Lan; Zhou, Liangxue; Zhang, Xiaoning; You, Chao; Guo, Gang

2015-01-01

Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol–gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs–hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs–hydrogel may have potential clinical applications. PMID:26664119

Bioinspired synthesis of magnetic nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, Anand

2009-01-01

The synthesis of magnetic nanoparticles has long been an area of active research. Magnetic nanoparticles can be used in a wide variety of applications such as magnetic inks, magnetic memory devices, drug delivery, magnetic resonance imaging (MRI) contrast agents, and pathogen detection in foods. In applications such as MRI, particle uniformity is particularly crucial, as is the magnetic response of the particles. Uniform magnetic particles with good magnetic properties are therefore required. One particularly effective technique for synthesizing nanoparticles involves biomineralization, which is a naturally occurring process that can produce highly complex nanostructures. Also, the technique involves mild conditions (ambientmore » temperature and close to neutral pH) that make this approach suitable for a wide variety of materials. The term 'bioinspired' is important because biomineralization research is inspired by the naturally occurring process, which occurs in certain microorganisms called 'magnetotactic bacteria'. Magnetotactic bacteria use biomineralization proteins to produce magnetite crystals having very good uniformity in size and morphology. The bacteria use these magnetic particles to navigate according to external magnetic fields. Because these bacteria synthesize high quality crystals, research has focused on imitating aspects of this biomineralization in vitro. In particular, a biomineralization iron-binding protein found in a certain species of magnetotactic bacteria, magnetospirillum magneticum, AMB-1, has been extracted and used for in vitro magnetite synthesis; Pluronic F127 gel was used to increase the viscosity of the reaction medium to better mimic the conditions in the bacteria. It was shown that the biomineralization protein mms6 was able to facilitate uniform magnetite synthesis. In addition, a similar biomineralization process using mms6 and a shorter version of this protein, C25, has been used to synthesize cobalt ferrite particles. The overall goal of this project is to understand the mechanism of magnetite particle synthesis in the presence of the biomineralization proteins, mms6 and C25. Previous work has hypothesized that the mms6 protein helps to template magnetite and cobalt ferrite particle synthesis and that the C25 protein templates cobalt ferrite formation. However, the effect of parameters such as the protein concentration on the particle formation is still unknown. It is expected that the protein concentration significantly affects the nucleation and growth of magnetite. Since the protein provides iron-binding sites, it is expected that magnetite crystals would nucleate at those sites. In addition, in the previous work, the reaction medium after completion of the reaction was in the solution phase, and magnetic particles had a tendency to fall to the bottom of the medium and aggregate. The research presented in this thesis involves solid Pluronic gel phase reactions, which can be studied readily using small-angle x-ray scattering, which is not possible for the solution phase experiments. In addition, the concentration effect of both of the proteins on magnetite crystal formation was studied.« less

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

NASA Astrophysics Data System (ADS)

Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

2011-12-01

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system.

PubMed

Gao, Qihe; Liang, Qing; Yu, Fei; Xu, Jian; Zhao, Qihua; Sun, Baiwang

2011-12-01

Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method. Copyright © 2011 Elsevier B.V. All rights reserved.

Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

NASA Astrophysics Data System (ADS)

Singh, Raman Preet; Jain, Sanyog; Ramarao, Poduri

2013-10-01

Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation.

Self-Assembling Block Copolymer Resist Mixtures towards Lithographic Resists for Sub-10 nm Features

NASA Astrophysics Data System (ADS)

Chandler, Curran; Daga, Vikram; Watkins, James

2009-03-01

Significant improvements in 193 nm photolithography have enabled the extension of device feature sizes beyond the 45 nm and 32 nm nodes, yet uncertainty lies beyond 22 nm features as no single replacement has emerged. Here we show that low molecular weight, nonionic block copolymer surfactant blends are capable of self-assembling into highly ordered domains with feature sizes on the order of 5 nm. These surfactants, most of which lack the required χN for microphase separation on their own, exhibit strong segregation and long-range order upon addition of a component capable of multi-point hydrogen bonding that is specific for one of the blocks in the copolymer. This has been demonstrated by our SAXS data for several Pluronic (PEO-b-PPO-b-PEO) and Brij (PEO-b-[CH2]nCH3) surfactants of various molecular weights and PEO volume fractions. Furthermore, we employ these highly-ordered systems as thin film, nanolithographic etch masks for the transfer of sub-10 nm patterns into silicon-based substrates. Small molecule, hydrogen bonding additives containing aromatic or silsesquioxane structure are also used to tune etch contrast between the blocks which is important for reducing line edge roughness (LER) of such small features.

Preparation and characterization of cellulose-based foams via microwave curing

PubMed Central

Demitri, Christian; Giuri, Antonella; Raucci, Maria Grazia; Giugliano, Daniela; Madaghiele, Marta; Sannino, Alessandro; Ambrosio, Luigi

2014-01-01

In this work, a mixture of a sodium salt of carboxymethylcellulose (CMCNa) and polyethylene glycol diacrylate (PEGDA700) was used for the preparation of a microporous structure by using the combination of two different procedures. First, physical foaming was induced using Pluronic as a blowing agent, followed by a chemical stabilization. This second step was carried out by means of an azobis(2-methylpropionamidine)dihydrochloride as the thermoinitiator (TI). This reaction was activated by heating the sample homogeneously using a microwave generator. Finally, the influence of different CMCNa and PEGDA700 ratios on the final properties of the foams was investigated. The viscosity, water absorption capacity, elastic modulus and porous structure were evaluated for each sample. In addition, preliminary biological characterization was carried out with the aim to prove the biocompatibility of the resulting material. The foam, including 20% of PEGDA700 in the mixture, demonstrated higher viscosity and stability before thermo-polymerization. In addition, increased water absorption capacity, mechanical resistance and a more uniform microporous structure were obtained for this sample. In particular, foam with 3% of CMCNa shows a hierarchical structure with open pores of different sizes. This morphology increased the properties of the foams. The full set of samples demonstrated an excellent biocompatibility profile with a good cell proliferation rate of more than 7 days. PMID:24501679

An Artificial Neural Network Based Analysis of Factors Controlling Particle Size in a Virgin Coconut Oil-Based Nanoemulsion System Containing Copper Peptide

PubMed Central

Samson, Shazwani; Basri, Mahiran; Fard Masoumi, Hamid Reza; Abdul Malek, Emilia; Abedi Karjiban, Roghayeh

2016-01-01

A predictive model of a virgin coconut oil (VCO) nanoemulsion system for the topical delivery of copper peptide (an anti-aging compound) was developed using an artificial neural network (ANN) to investigate the factors that influence particle size. Four independent variables including the amount of VCO, Tween 80: Pluronic F68 (T80:PF68), xanthan gum and water were the inputs whereas particle size was taken as the response for the trained network. Genetic algorithms (GA) were used to model the data which were divided into training sets, testing sets and validation sets. The model obtained indicated the high quality performance of the neural network and its capability to identify the critical composition factors for the VCO nanoemulsion. The main factor controlling the particle size was found out to be xanthan gum (28.56%) followed by T80:PF68 (26.9%), VCO (22.8%) and water (21.74%). The formulation containing copper peptide was then successfully prepared using optimum conditions and particle sizes of 120.7 nm were obtained. The final formulation exhibited a zeta potential lower than -25 mV and showed good physical stability towards centrifugation test, freeze-thaw cycle test and storage at temperature 25°C and 45°C. PMID:27383135

An Artificial Neural Network Based Analysis of Factors Controlling Particle Size in a Virgin Coconut Oil-Based Nanoemulsion System Containing Copper Peptide.

PubMed

Samson, Shazwani; Basri, Mahiran; Fard Masoumi, Hamid Reza; Abdul Malek, Emilia; Abedi Karjiban, Roghayeh

2016-01-01

A predictive model of a virgin coconut oil (VCO) nanoemulsion system for the topical delivery of copper peptide (an anti-aging compound) was developed using an artificial neural network (ANN) to investigate the factors that influence particle size. Four independent variables including the amount of VCO, Tween 80: Pluronic F68 (T80:PF68), xanthan gum and water were the inputs whereas particle size was taken as the response for the trained network. Genetic algorithms (GA) were used to model the data which were divided into training sets, testing sets and validation sets. The model obtained indicated the high quality performance of the neural network and its capability to identify the critical composition factors for the VCO nanoemulsion. The main factor controlling the particle size was found out to be xanthan gum (28.56%) followed by T80:PF68 (26.9%), VCO (22.8%) and water (21.74%). The formulation containing copper peptide was then successfully prepared using optimum conditions and particle sizes of 120.7 nm were obtained. The final formulation exhibited a zeta potential lower than -25 mV and showed good physical stability towards centrifugation test, freeze-thaw cycle test and storage at temperature 25°C and 45°C.

Boron and Poloxamer (F68 and F127) Containing Hydrogel Formulation for Burn Wound Healing.

PubMed

Demirci, Selami; Doğan, Ayşegül; Karakuş, Emre; Halıcı, Zekai; Topçu, Atila; Demirci, Elif; Sahin, Fikrettin

2015-11-01

Burn injuries, the most common and destructive forms of wounds, are generally accompanied with life-threatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process. Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.

Towards vaporized molecular discrimination: a quartz crystal microbalance (QCM) sensor system using cobalt-containing mesoporous graphitic carbon.

PubMed

Tang, Jing; Torad, Nagy L; Salunkhe, Rahul R; Yoon, Jang-Hee; Al Hossain, Md Shahriar; Dou, Shi Xue; Kim, Jung Ho; Kimura, Tatsuo; Yamauchi, Yusuke

2014-11-01

A recent study on nanoporous carbon based materials (J. Am. Chem. Soc. 2012, 134, 2864) showed that the presence of abundant graphitized sp(2) carbon species in the frameworks led to higher affinity for aromatic hydrocarbons than their aliphatic analogues. Herein, improved understanding of the sensitive and selective detection of aromatic substances by using mesoporous carbon (MPC)-based materials, combined with a quartz crystal microbalance (QCM) sensor system, was obtained. MPCs were synthesized by direct carbonization of mesoporous polymers prepared from resol through a soft templating approach with Pluronic F127. The carbon-based frameworks can be graphitized through the addition of a cobalt source to the precursor solution, according to the catalytic activity of the cobalt nanoparticles formed during the carbonization process. From the Raman data, the degree of the graphitization was clearly increased by increasing the cobalt content and elevating the carbonization temperature. From a QCM study, it was proved that the highly graphitized MPCs exhibited a higher affinity for aromatic hydrocarbons than their aliphatic analogues. By increasing the degree of graphitization in the carbon-based pore walls, the MPCs showed both larger adsorption uptake and faster sensor response towards toxic benzene and toluene vapors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hematite Thin Films with Various Nanoscopic Morphologies Through Control of Self-Assembly Structures

NASA Astrophysics Data System (ADS)

Liu, Jingling; Kim, Yong-Tae; Kwon, Young-Uk

2015-05-01

Hematite (α-Fe2O3) thin films with various nanostructures were synthesized through self-assembly between iron oxide hydroxide particles, generated by hydrolysis and condensation of Fe(NO3)3 · 6H2O, and a Pluronic triblock copolymer (F127, (EO)106(PO)70(EO)106, EO = ethylene oxide, PO = propylene oxide), followed by calcination. The self-assembly structure can be tuned by introducing water in a controlled manner through the control of the humidity level in the surrounding of the as-cast films during aging stage. For the given Fe(NO3)3 · 6H2O:F127 ratio, there appear to be three different thermodynamically stable self-assembly structures depending on the water content in the film material, which correspond to mesoporous, spherical micellar, and rod-like micellar structures after removal of F127. Coupled with the thermodynamic driving forces, the kinetics of the irreversible reactions of coalescence of iron oxide hydroxide particles into larger ones induce diverse nanostructures of the resultant films. The length scale of so-obtained nanostructures ranges from 6 nm to a few hundred nanometers. In addition to water content, the effects of other experimental parameters such as aging temperature, spin rate during spin coating, type of substrate, and type of iron reagent were investigated.

Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy

PubMed Central

Oh, Keun Sang; Kim, Kyungim; Yoon, Byeong Deok; Lee, Hye Jin; Park, Dal Yong; Kim, Eun-yeong; Lee, Kiho; Seo, Jae Hong; Yuk, Soon Hong

2016-01-01

A mixture of docetaxel (DTX) and Solutol® HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects. PMID:27042062

The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

PubMed

Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

2010-01-04

Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery.

PubMed

Wahlberg, Brendon; Ghuman, Harmanvir; Liu, Jessie R; Modo, Michel

2018-06-15

Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood. We here detailed the biomechanical forces (pressure, shear stress) that cells are exposed to during ejection through different sized needles (20G, 26G, 32G) and syringes (10, 50, 250 µL) at relevant flow rates (1, 5, 10 µL/min). A comparison of 3 vehicles, Phosphate Buffered Saline (PBS), Hypothermosol (HTS), and Pluronic, indicated that less viscous vehicles are favorable for suspension with a high cell volume fraction to minimize sedimentation. Higher suspension viscosity was associated with greater shear stress. Higher flow rates with viscous vehicle, such as HTS reduced viability by ~10% and also produced more apoptotic cells (28%). At 5 µL/min ejection using a 26G needle increased neuronal differentiation for PBS and HTS suspensions. These results reveal the biological impact of biomechanical forces in the cell delivery process. Appropriate engineering strategies can be considered to mitigate these effects to ensure the efficacious translation of this promising therapy.

Stabilized micelles as delivery vehicles for paclitaxel.

PubMed

Yoncheva, Krassimira; Calleja, Patricia; Agüeros, Maite; Petrov, Petar; Miladinova, Ivanka; Tsvetanov, Christo; Irache, Juan M

2012-10-15

Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol(®)), longer mean residence time (9-times longer than i.v. Taxol(®)) and high distribution volume (2-fold higher than i.v. Taxol(®)) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol(®), in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles. Copyright © 2012 Elsevier B.V. All rights reserved.

Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

PubMed

Kim, Joong-Hyun; Oh, Se Heang; Min, Hyun Ki; Lee, Jin Ho

2018-01-01

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018. © 2017 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rana, Vijay Kumar; Department of Chemical Technology, North Maharashtra University Jalgaon-425001; Division of Polymer Science and Engineering, National Chemical Laboratory, Pune-411 008

To achieve a high level of heavy metal adsorption, 1,1 Prime ,1 Double-Prime -(1,3,5-triazine-2,4,6-triyl)tris(3-(3-(triethoxysilyl)propyl)urea) (TTPU) was synthesized as a novel melamine precursor and incorporated on the silica surface of periodic mesoporous organosilica (PMO). The melamine modified PMOs (MPMOs) were synthesized under acidic conditions using TTPU, tetraethylorthosilicate (TEOS) and Pluronic P123 as a template and the modified PMOs were characterized using the relevant instrumental techniques. The characteristic materials were used as adsorbents for the adsorption of Fe(III) ions. Fe(III) adsorption studies revealed MPMO-7.5 to be a good absorbent with higher adsorption efficiency than other MPMOs. - Graphical Abstract: A new organosilicamore » precursor, TTPU, has been successfully synthesized and characterized to incorporate on the silica surface of periodic mesoporous organosilica (PMO). The melamine modified PMOs (MPMOs), in particular, the MPMO-7.5 was found to exhibit good adsorption efficiency for Fe(III). Highlights: Black-Right-Pointing-Pointer Synthesis of new melamine modified periodic mesoporous organosilicas (MPMOs). Black-Right-Pointing-Pointer A new organosilica precursor, TTPU, has been successfully synthesized for the MPMOs. Black-Right-Pointing-Pointer The MPMOs were characterized by the relevant instrumental techniques. Black-Right-Pointing-Pointer MPMO-7.5 exhibits higher adsorption efficiency for Fe(III) ions than other MPMOs.« less

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

2017-03-30

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures. Copyright © 2017 Elsevier B.V. All rights reserved.

Thermoreversible Morphology and Conductivity of a Conjugated Polymer Network Embedded in Block Copolymer Self-Assemblies

DOE PAGES

Han, Youngkyu; Carrillo, Jan-Michael Y.; Zhang, Zhe; ...

2016-07-19

Self-assembly of block copolymers provides numerous opportunities to create functional materials, utilizing self-assembled microdomains with a variety of morphology and periodic architectures as templates for functional nanofillers. Here new progress is reported toward the fabrication of thermally responsive and electrically conductive polymeric self-assemblies made from a water-soluble poly(thiophene) derivative with short poly(ethylene oxide) side chains and Pluronic L62 block copolymer solution in water. The structural and electrical properties of conjugated polymer-embedded self-assembled architectures are investigated by combining small-angle neutron and X-ray scattering, coarse-grained molecular dynamics simulations, and impedance spectroscopy. The L62 solution template organizes the conjugated polymers by stably incorporatingmore » them into the hydrophilic domains thus inhibiting aggregation. The changing morphology of L62 during the micellarto- lamellar phase transition defines the embedded conjugated polymer network. As a result, the conductivity is strongly coupled to the structural change of the templating L62 phase and exhibits thermally reversible behavior with no signs of quenching of the conductivity at high temperature. In conclusion, this study shows promise for enabling more flexibility in processing and utilizing water-soluble conjugated polymers in aqueous solutions for self-assembly based fabrication of stimuli-responsive nanostructures and sensory materials.« less

Thermoreversible Morphology and Conductivity of a Conjugated Polymer Network Embedded in Block Copolymer Self-Assemblies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Youngkyu; Carrillo, Jan-Michael Y.; Zhang, Zhe

Self-assembly of block copolymers provides numerous opportunities to create functional materials, utilizing self-assembled microdomains with a variety of morphology and periodic architectures as templates for functional nanofillers. Here new progress is reported toward the fabrication of thermally responsive and electrically conductive polymeric self-assemblies made from a water-soluble poly(thiophene) derivative with short poly(ethylene oxide) side chains and Pluronic L62 block copolymer solution in water. The structural and electrical properties of conjugated polymer-embedded self-assembled architectures are investigated by combining small-angle neutron and X-ray scattering, coarse-grained molecular dynamics simulations, and impedance spectroscopy. The L62 solution template organizes the conjugated polymers by stably incorporatingmore » them into the hydrophilic domains thus inhibiting aggregation. The changing morphology of L62 during the micellarto- lamellar phase transition defines the embedded conjugated polymer network. As a result, the conductivity is strongly coupled to the structural change of the templating L62 phase and exhibits thermally reversible behavior with no signs of quenching of the conductivity at high temperature. In conclusion, this study shows promise for enabling more flexibility in processing and utilizing water-soluble conjugated polymers in aqueous solutions for self-assembly based fabrication of stimuli-responsive nanostructures and sensory materials.« less

Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol

NASA Astrophysics Data System (ADS)

Zhao, Qinfu; Wang, Tianyi; Wang, Jing; Zheng, Li; Jiang, Tongying; Cheng, Gang; Wang, Siling

2011-09-01

In order to improve the dissolution rate and increase the bioavailability of a poorly water-soluble drug, intended to be administered orally, the biocompatible and bioactive mesoporous hydroxyapatite (HA) was successfully synthesized. In the present study, mesoporous HA nanoparticles were produced using Pluronic block co-polymer F127 and cetyltrimethylammonium bromide (CTAB) as templates by the hydrothermal method. The obtained mesoporous HA was employed as a drug delivery carrier to investigate the drug storage/release properties using carvedilol (CAR) as a model drug. Characterizations of the raw CAR powder, mesoporous HA and CAR-loaded HA were carried out by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, N2 adsorption/desorption, thermogravimetric analysis (TGA), and UV-VIS spectrophotometry. The results demonstrated that CAR was successfully incorporated into the mesoporous HA host. In vitro drug release studies showed that mesoporous HA had a high drug load efficiency and provided immediate release of CAR compared with micronized raw drug in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). Consequently, mesoporous HA is a good candidate as a drug carrier for the oral delivery of poorly water-soluble drugs.

Magnetic nanoparticles and thermally responsive polymer for targeted hyperthermia and sustained anti-cancer drug delivery.

PubMed

Wang, Sarah Y; Liu, Michelle C; Kang, Kyung A

2013-01-01

A novel cancer treatment method is being designed using a combination of iron oxide (Fe(3)O(4)) nanoparticles (IONPs) and Pluronic F-127 (PF127). IONPs have been used for heating tumors via an alternating electromagnetic (AEM) field. PF127 is a polymer possessing thermo-reversible and concentration-dependent gelation properties in aqueous solutions. PF127, as a gel, is an attractive drug delivery vehicle due to its zero-order drug release property. The combination of IONPs and PF127 would allow both short-term, tumor-specific, hyperthermic treatment, and long-term sustained drug delivery. As a preliminary study, the gelling and heating properties of IONPs/PF127 mixtures were investigated: 18% (w/w) PF127 was found to be ideal for our purpose because it gels at 28.0°C, i.e., it would be injectable at room temperature (20-25°C) and forms gel upon injection into the body (37°C). IONPs in PF127 showed little effect on gelation temperatures. The heating performance of IONPs in PF127 slightly, but linearly decreased with PF127. In the IONP concentration range of 0.01-0.05% (w/v) mixed with PF127 at 18% (w/w), the heating performance increased linearly with the increase in IONP concentration.

Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy.

PubMed

Xu, Wujun; Thapa, Rinez; Liu, Dongfei; Nissinen, Tuomo; Granroth, Sari; Närvänen, Ale; Suvanto, Mika; Santos, Hélder A; Lehto, Vesa-Pekka

2015-11-02

In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.

Evaluation of molecular volume change of block copolymer depending on temperature: A SANS study

DOE PAGES

Kim, Tae-Hwan; Do, Changwoo; Han, Young-Soo

2017-12-24

Amphiphilic Pluronic triblock copolymers form various self-assembled structures such as sphere, cylinder, lamellae and so on, depending on temperature, leading to the increase of hydrophobicity of block copolymers. However, the effective molecular volume change of the block copolymer has not been fully exploited yet, when temperature increases. Here in this paper, we have investigated the effective molecular volume change of the block copolymer upon heating by using the contrast variation small angle neutron scattering. The scattering length densities (SLDs) of the block copolymer were experimentally obtained from the neutron scattering contrast variation method between the solvent and the block copolymermore » at varying temperature. Even though the SLD, which is the intrinsic property of the material, should not be changed by temperature elevation, it was dependent on temperature, indicating that the molecular volume is changed. Therefore, we obtained the increase rate of the molecular volume change of the block copolymer (the effective molecular volume change) from the comparison of the calculated SLD and the standard SLD, which is evaluated by plotting the SANS intensity at the first order Bragg peak as the function of temperature at each volume fraction of D 2O and H 2O that is about 25.5%–51.3% depending on temperature.« less

Evaluation of molecular volume change of block copolymer depending on temperature: A SANS study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Tae-Hwan; Do, Changwoo; Han, Young-Soo

Amphiphilic Pluronic triblock copolymers form various self-assembled structures such as sphere, cylinder, lamellae and so on, depending on temperature, leading to the increase of hydrophobicity of block copolymers. However, the effective molecular volume change of the block copolymer has not been fully exploited yet, when temperature increases. Here in this paper, we have investigated the effective molecular volume change of the block copolymer upon heating by using the contrast variation small angle neutron scattering. The scattering length densities (SLDs) of the block copolymer were experimentally obtained from the neutron scattering contrast variation method between the solvent and the block copolymermore » at varying temperature. Even though the SLD, which is the intrinsic property of the material, should not be changed by temperature elevation, it was dependent on temperature, indicating that the molecular volume is changed. Therefore, we obtained the increase rate of the molecular volume change of the block copolymer (the effective molecular volume change) from the comparison of the calculated SLD and the standard SLD, which is evaluated by plotting the SANS intensity at the first order Bragg peak as the function of temperature at each volume fraction of D 2O and H 2O that is about 25.5%–51.3% depending on temperature.« less

Novel formulations enhance the thermal stability of live-attenuated flavivirus vaccines

PubMed Central

Wiggan, O’Neil; Silengo, Shawn J.; Kinney, Richard M.; Osorio, Jorge E.; Huang, Claire Y.-H.; Stinchcomb, Dan T.

2011-01-01

Thermal stability is important for the manufacture, distribution and administration of vaccines, especially in tropical developing countries, where particularly adverse field conditions exist. Current live-attenuated flavivirus vaccines exhibit relatively poor liquid stability in clinical settings, and clinicians are instructed to discard the yellow fever vaccine 1h after reconstitution. We have identified novel combinations of excipients that greatly enhance the thermal stability of live-attenuated DEN-2 PDK-53-based flavivirus vaccine candidates. Liquid formulations comprising a sugar, albumin and a pluronic polymer minimized the loss of flavivirus infectious titer to less than 0.5log(10)pfu after storage for at least 8h at 37°C, 7 days at room temperature or at least 11 weeks at 4°C. Additionally, these formulations prevented reduction of viral infectivity after two freeze-thaw cycles of virus. Formulated candidate vaccines were readily lyophilized and reconstituted with minimal loss of viral titers. In mice, the formulations were safe and did not hinder the ability of the vaccine virus to generate a potent, protective immune response. These formulations provided significantly greater liquid-phase stability than has been reported previously for other flavivirus vaccine formulations. The enhanced thermal stability provided by the formulations described here will facilitate the effective distribution of flavivirus vaccines worldwide. PMID:21803103

Phase behavior and dynamics of a micelle-forming triblock copolymer system

NASA Astrophysics Data System (ADS)

Mohan, P. Harsha; Bandyopadhyay, Ranjini

2008-04-01

Synperonic F-108 (generic name, “pluronic”) is a micelle forming triblock copolymer of type ABA , where A is polyethylene oxide (PEO) and B is polypropylene oxide (PPO). At high temperatures, the hydrophobicity of the PPO chains increase, and the pluronic molecules, when dissolved in an aqueous medium, self-associate into spherical micelles with dense PPO cores and hydrated PEO coronas. At appropriately high concentrations, these micelles arrange in a face centered cubic lattice to show inverse crystallization, with the samples exhibiting high-temperature crystalline and low-temperature fluidlike phases. By studying the evolution of the elastic and viscous moduli as temperature is increased at a fixed rate, we construct the concentration-temperature phase diagram of Synperonic F-108. For a certain range of temperatures and at appropriate sample concentrations, we observe a predominantly elastic response. Oscillatory strain amplitude sweep measurements on these samples show pronounced peaks in the loss moduli, a typical feature of soft solids. The soft solidlike nature of these materials is further demonstrated by measuring their frequency-dependent mechanical moduli. The storage moduli are significantly larger than the loss moduli and are almost independent of the applied angular frequency. Finally, we perform strain rate frequency superposition experiments to measure the slow relaxation dynamics of this soft solid.

Magnetic Nanoparticles with Dual Functional Properties: Drug Delivery and Magnetic Resonance Imaging

PubMed Central

Jain, Tapan K.; Richey, John; Strand, Michelle; Leslie-Pelecky, Diandra L.; Flask, Chris; Labhasetwar, Vinod

2008-01-01

There is significant interest in recent years in developing MNPs having multifunctional characteristics with complimentary roles. In this study, we investigated the drug delivery and magnetic resonance imaging (MRI) properties of our novel oleic acid-coated iron-oxide and pluronic-stabilized magnetic nanoparticles (MNPs). The drug incorporation efficiency of doxorubicin and paclitaxel (alone or in combination) in MNPs was 74–95%; the drug release was sustained and the incorporated drugs had marginal effects on physical (size and zeta potential) or magnetization properties of the MNPs. The drugs in combination incorporated in MNPs demonstrated highly synergistic antiproliferative activity in breast cancer cells. The T2 relaxivity (r2) was higher for our MNPs than Feridex IV, whereas the T1 relaxivity (r1) was better for Feridex IV than for our MNPs, suggesting greater sensitivity of our MNPs than Feridex IV in T2 weighted imaging. The circulation half-life (t1/2), determined from the changes in the MRI signal intensity in carotid arteries in mice, was longer for our MNPs than Feridex IV (t1/2 = 31.2 vs 6.4 min). MNPs with combined characteristics of MRI and drug delivery could be of high clinical significance in the treatment of various disease conditions. PMID:18649936

One-Pot synthesis of phosphorylated mesoporous carbon heterogeneous catalysts with tailored surface acidity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fulvio, Pasquale F; Mahurin, Shannon Mark; Mayes, Richard T

2012-01-01

Soft-templated phosphorylated mesoporous carbons with homogeneous distributions of phosphate groups were prepared by a 'one-pot' synthesis method using mixtures of phosphoric acid with hydrochloric, or nitric acids in the presence of Pluronic F127 triblock copolymer. Adjusting the various ratios of phosphoric acid used in these mixtures resulted in carbons with distinct adsorption, structural and surface acidity properties. The pore size distributions (PSDs) from nitrogen adsorption at -196 C showed that mesoporous carbons exhibit specific surface areas as high as 551 m{sup 2}/g and mesopores as large as 13 nm. Both structural ordering of the mesopores and the final phosphate contentsmore » were strongly dependent on the ratios of H{sub 3}PO{sub 4} in the synthesis gels, as shown by transmission electron microscopy (TEM), X-ray photoelectron (XPS) and energy dispersive X-ray spectroscopy (EDS). The number of surface acid sites determined from temperature programmed desorption of ammonia (NH{sub 3}-TPD) were in the range of 0.3-1.5 mmol/g while the active surface areas are estimated to comprise 5-54% of the total surface areas. Finally, the conversion temperatures for the isopropanol dehydration were lowered by as much as 100 C by transitioning from the least acidic to the most acidic catalysts surface.« less

Brain delivery of proteins via their fatty acid and block copolymer modifications

PubMed Central

Yi, Xiang; Kabanov, Alexander V.

2014-01-01

It is well known that hydrophobic small molecules penetrate cell membranes better than hydrophilic molecules. Amphiphilic molecules that dissolve both in lipid and aqueous phases are best suited for membrane transport. Transport of biomacromolecules across physiological barriers, e.g. the blood-brain barrier, is greatly complicated by the unique structure and function of such barriers. Two decades ago we adopted a simple philosophy that to increase protein delivery to the brain one needs to modify this protein with hydrophobic moieties. With this general idea we began modifying proteins (antibodies, enzymes, hormones, etc.) with either hydrophobic fatty acid residues or amphiphilic block copolymer moieties, such as poy(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (pluronics or poloxamers) and more recently, poly(2-oxasolines). This simple approach has resulted in impressive successes in CNS drug delivery. We present a retrospective overview of these works initiated in the Soviet Union in 1980s, and then continued in the United States and other countries. Notably some of the early findings were later corroborated by brain pharmacokinetic data. Industrial development of several drug candidates employing these strategies has followed. Overall modification by hydrophobic fatty acids residues or amphiphilic block copolymers represents a promising and relatively safe strategy to deliver proteins to the brain. PMID:24160902

Transdermal iontophoresis of ranitidine: an opportunity in paediatric drug therapy.

PubMed

Djabri, Asma; Guy, Richard H; Delgado-Charro, M Begoña

2012-10-01

The objective of this study was to examine the use of transdermal iontophoresis for the delivery of ranitidine hydrochloride in children. Constant, direct current, anodal iontophoresis of ranitidine was performed in vitro across dermatomed pig skin. The effect of donor vehicle, current intensity, and drug concentration were first examined using aqueous solutions. It was found that drug delivery was higher at pH 7 (donor: 5mM Tris) than pH 5.6 (donor: water). In the presence of low levels of competing background electrolyte, ranitidine delivery increased linearly with applied current but was independent of the donor drug concentration. The second part of the study evaluated two Pluronic(®) F-127 gels as potential vehicles for ranitidine delivery. The formulations were characterised in terms of apparent viscosity, conductivity and passive permeation measurements. Iontophoretic delivery of ranitidine was only slightly affected when delivered from the gels relative to aqueous solutions. Overall the results demonstrated that therapeutic paediatric doses of ranitidine (neonates: 0.09-0.17 μmol/kg h; 1 month to 12 years: 0.36-0.71 μmol/kg h) could be easily achieved by transdermal iontophoresis with simple gel patches of practical surface area (0.2-1.5 cm(2)/kg). Copyright © 2012 Elsevier B.V. All rights reserved.

Surface-Enhanced Raman Scattering Active Plasmonic Nanoparticles with Ultrasmall Interior Nanogap for Multiplex Quantitative Detection and Cancer Cell Imaging.

PubMed

Li, Jiuxing; Zhu, Zhi; Zhu, Bingqing; Ma, Yanli; Lin, Bingqian; Liu, Rudi; Song, Yanling; Lin, Hui; Tu, Song; Yang, Chaoyong

2016-08-02

Due to its large enhancement effect, nanostructure-based surface-enhanced Raman scattering (SERS) technology had been widely applied for bioanalysis and cell imaging. However, most SERS nanostructures suffer from poor signal reproducibility, which hinders the application of SERS nanostructures in quantitative detection. We report an etching-assisted approach to synthesize SERS-active plasmonic nanoparticles with 1 nm interior nanogap for multiplex quantitative detection and cancer cell imaging. Raman dyes and methoxy poly(ethylene glycol) thiol (mPEG-SH) were attached to gold nanoparticles (AuNPs) to prepare gold cores. Next, Ag atoms were deposited on gold cores in the presence of Pluronic F127 to form a Ag shell. HAuCl4 was used to etch the Ag shell and form an interior nanogap in Au@AgAuNPs, leading to increased Raman intensity of dyes. SERS intensity distribution of Au@AgAuNPs was found to be more uniform than that of aggregated AuNPs. Finally, Au@AgAuNPs were used for multiplex quantitative detection and cancer cell imaging. With the advantages of simple and rapid preparation of Au@AgAuNPs with highly uniform, stable, and reproducible Raman intensity, the method reported here will widen the applications of SERS-active nanoparticles in diagnostics and imaging.

Synthesis and structure of pyridine-functionalized mesoporous SBA-15 organosilicas and their application for sorption of diclofenac

NASA Astrophysics Data System (ADS)

Barczak, Mariusz

2018-02-01

A series of pyridine-functionalized mesoporous silicas have been prepared for the first time via direct co-condensation of tetraethoxysilane (TEOS) and 2-(2-pyridyl)ethyltrimethoxysilane (PETS) using the block copolymer Pluronic P123 as a structure-directing agent. The obtained materials were fully characterized by a wide range of instrumental techniques and employed as adsorbents for the removal of a diclofenac which is considered a priority hazardous drug. The synthesized materials exhibit a high adsorption capacities and rapid adsorption rates. The structural and adsorption properties depend largely on the relative amount of PETS/TEOS ratio: the gradual degradation of ordered structure and porosity was observed with the increasing amount of PETS. However due to the highest loading of pyridine units the most structurally degraded material had the highest adsorption uptake (631 mg g-1) indicating that the surface chemistry plays - along with porosity - an important role in governing the adsorption process. The experimental adsorption data were modelled using the Langmuir, Freundlich and Langmuir-Freundlich isotherms - among them the Langmuir-Freundlich model turned out to be the most suitable for describing adsorption behaviour of diclofenac onto the materials. The collected data show that the pyridine-functionalized mesoporous silicas can be a promising absorbent of pharmaceuticals.

Acid-Labile Amphiphilic PEO-b-PPO-b-PEO Copolymers: Degradable Poloxamer Analogs.

PubMed

Worm, Matthias; Kang, Biao; Dingels, Carsten; Wurm, Frederik R; Frey, Holger

2016-05-01

Poly ((ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)) triblock copolymers commonly known as poloxamers or Pluronics constitute an important class of nonionic, biocompatible surfactants. Here, a method is reported to incorporate two acid-labile acetal moieties in the backbone of poloxamers to generate acid-cleavable nonionic surfactants. Poly(propylene oxide) is functionalized by means of an acetate-protected vinyl ether to introduce acetal units. Three cleavable PEO-PPO-PEO triblock copolymers (Mn,total = 6600, 8000, 9150 g·mol(-1) ; Mn,PEO = 2200, 3600, 4750 g·mol(-1) ) have been synthesized using anionic ring-opening polymerization. The amphiphilic copolymers exhibit narrow molecular weight distributions (Ð = 1.06-1.08). Surface tension measurements reveal surface-active behavior in aqueous solution comparable to established noncleavable poloxamers. Complete hydrolysis of the labile junctions after acidic treatment is verified by size exclusion chromatography. The block copolymers have been employed as surfactants in a miniemulsion polymerization to generate polystyrene (PS) nanoparticles with mean diameters of ≈200 nm and narrow size distribution, as determined by dynamic light scattering and scanning electron microscopy. Acid-triggered precipitation facilitates removal of surfactant fragments from the nanoparticles, which simplifies purification and enables nanoparticle precipitation "on demand." © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CO₂ adsorption on amine-functionalized periodic mesoporous benzenesilicas.

PubMed

Sim, Kyohyun; Lee, Nakwon; Kim, Joonseok; Cho, Eun-Bum; Gunathilake, Chamila; Jaroniec, Mietek

2015-04-01

CO2 adsorption was investigated on amine-functionalized mesoporous silica (SBA-15) and periodic mesoporous organosilica (PMO) samples. Hexagonally (p6mm) ordered mesoporous SBA-15 and benzene-PMO (BPMO) samples were prepared in the presence of Pluronic P123 block copolymer template under acidic conditions. Three kinds of amine-containing organosilanes and polyethylenimine were used to functionalize SBA-15 and BPMO. Small-angle X-ray scattering and nitrogen adsorption isotherms showed that these samples featured ordered mesostructure, high surface area, and narrow pore size distributions. Solid-state (13)C- and (29)Si cross-polarization magic-angle spinning NMR spectra showed chemical linkage between amine-containing modifiers and the surface of mesoporous materials. The chemically linked amine-containing modifiers were found to be on both the inner and outer surfaces. N-[3-(trimethoxysilyl)propyl]ethylenediamine-modified BPMO (A2-BPMO) sample exhibited the highest CO2 uptake (i.e., ∼3.03 mmol/g measured on a volumetric adsorption analyzer) and the fastest adsorption rate (i.e., ∼13 min to attain 90% of the maximum amount) among all the samples studied. Selectivity and reproducibility measurements for the A2-BPMO sample showed quite good performance in flowing N2 gas at 40 mL/min and CO2 gas of 60 mL/min at 25 °C.

Root-Knot Nematodes Exhibit Strain-Specific Clumping Behavior That Is Inherited as a Simple Genetic Trait

PubMed Central

Wang, Congli; Lower, Steven; Thomas, Varghese P.; Williamson, Valerie M.

2010-01-01

Root-knot nematodes are obligate parasites of a wide range of plant species and can feed only on the cytoplasm of living plant cells. In the absence of a suitable plant host, infective juveniles of strain VW9 of the Northern root-knot nematode, Meloidogyne hapla, when dispersed in Pluronic F-127 gel, aggregate into tight, spherical clumps containing thousands of worms. Aggregation or clumping behavior has been observed in diverse genera in the phylum Nematoda spanning free-living species such as Caenorhabditis elegans as well as both plant and animal parasites. Clumping behavior differs between strains of M. hapla and occurs with other species within this genus where strain-specific differences in clumping ability are also apparent. Exposure of M. hapla juveniles to a gradient formed using low levels of cyanide promotes formation of clumps at a preferred cyanide level. Analysis of F2 lines from a cross of M. hapla strains that differ in clump-forming behavior reveals that the behavior segregates as a single, major locus that can be positioned on the genetic map of this nematode. Clumping behavior may be a survival strategy whose importance and function depend on the niche of the nematode strain or species. PMID:21151553

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

PubMed

Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

2013-12-31

Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.

Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

PubMed Central

Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

2014-01-01

Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro.

PubMed

Demirci, Selami; Doğan, Ayşegül; Türkmen, Neşe Başak; Telci, Dilek; Rizvanov, Albert A; Şahin, Fikrettin

2017-02-01

Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Carbon dioxide capture by activated methyl diethanol amine impregnated mesoporous carbon

NASA Astrophysics Data System (ADS)

Ardhyarini, N.; Krisnandi, Y. K.

2017-07-01

Activated Methyl Diethanol Amine (aMDEA) were impregnated onto the surface of the mesoporous carbon to increase carbon dioxide (CO2) adsorption capacity. The mesoporous carbon was synthesized through soft template method with phloroglucinol as carbon precursor and triblock copolymer (Pluronic F127) as structure directing agent. These activated MDEA impregnated mesoporous carbon (aMDEA-MC) were characterized using various solid characterization techniques. CO2 adsorption was investigated using autoclaved-reactor in the batch system. The FTIR spectrum of aMDEA-MC had absorption peaks at 3395 cm-1 and 1031 cm-1 which are characteristic for O-H stretch and amine C-N stretch in MDEA. The elemental analyzer showed that nitrogen content on the mesoporous carbon increased after impregnation by 23 wt.%. The BET surface area and total pore volume of mesoporous carbon decreased after impregnation, 43 wt.% and 50 wt.%, respectively. The maximum CO2 adsorption capacity of aMDEA43-MC was 2.63 mmol/g (298 K, 5 psi and pure CO2). This is 64 % and 35 % higher compared to the CO2 adsorption capacity of the starting MC and also commercially available activated carbon with higher surface area. All the results suggest that MDEA-MC is a promising adsorbent for CO2 capture.

Facile fabrication of bowl-shaped microparticles for oral curcumin delivery to ulcerative colitis tissue.

PubMed

Chen, Qiubing; Gou, Shuangquan; Huang, Yamei; Zhou, Xin; Li, Qian; Han, Moon Kwon; Kang, Yuejun; Xiao, Bo

2018-05-05

Oral microparticles (MPs) have been considered as promising drug carriers in the treatment of ulcerative colitis (UC). Here, a facile strategy based on a conventional emulsion-solvent evaporation technique was used to fabricate bowl-shaped MPs (BMPs), and these MPs loaded with anti-inflammatory drug (curcumin, CUR) during the fabrication process. The physicochemical properties of the resultant BMPs were characterized by dynamic light scattering, scanning electron microscope, confocal laser scanning microscope and X-ray diffraction as well as contact angle goniometer. Results indicated that BMPs had a desirable hydrodynamic diameter (1.84 ± 0.20 μm), a negative zeta potential (-26.5 ± 1.13 mV), smooth surface morphology, high CUR encapsulation efficiency and controlled drug release profile. It was found that CUR molecules were dispersed in an amorphous state within the polymeric matrixes. In addition, BMPs showed excellent hydrophilicity due to the presence of Pluronic F127 and poly(vinyl alcohol) on their surface. More importantly, orally administered BMPs could efficiently alleviate UC based on a dextran sulfate sodium-induced mouse model. These results collectively suggest that BMP can be exploited as a readily scalable oral drug delivery system for UC therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs.

PubMed

Yin, Xuezhi; Daintree, Linda Sharon; Ding, Sheng; Ledger, Daniel Mark; Wang, Bing; Zhao, Wenwen; Qi, Jianping; Wu, Wei; Han, Jiansheng

2015-01-01

This research aimed to develop a supercritical fluid (SCF) technique for preparing a particulate form of itraconazole (ITZ) with good dissolution and bioavailability characteristics. The ITZ particulate solid dispersion was formulated with hydroxypropyl methylcellulose, Pluronic F-127, and L-ascorbic acid. Aggregated particles showed porous structure when examined by scanning electron microscopy. Powder X-ray diffraction and Fourier transform infrared spectra indicated an interaction between ITZ and excipients and showed that ITZ existed in an amorphous state in the composite solid dispersion particles. The solid dispersion obtained by the SCF process improved the dissolution of ITZ in media of pH 1.0, pH 4.5, and pH 6.8, compared with a commercial product (Sporanox(®)), which could be ascribed to the porous aggregated particle shape and amorphous solid state of ITZ. While the solid dispersion did not show a statistical improvement (P=0.50) in terms of oral bioavailability of ITZ compared with Sporanox(®), the C max (the maximum plasma concentration of ITZ in a pharmacokinetic curve) of ITZ was raised significantly (P=0.03) after oral administration. Thus, the SCF process has been shown to be an efficient, single step process to form ITZ-containing solid dispersion particles with good dissolution and oral bioavailability characteristics.

Development of a multilayered association polymer system for sequential drug delivery

NASA Astrophysics Data System (ADS)

Chinnakavanam Sundararaj, Sharath kumar

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and antiinflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. KEYWORDS: Multiple drug delivery, Periodontitis, Cellulose acetate phthalate, Pluronic F-127, Sequential drug release, in vitro drug release, in vivo drug release.

Employment of cationic solid-lipid nanoparticles as RNA carriers.

PubMed

Montana, Giovanna; Bondì, Maria L; Carrotta, Rita; Picone, Pasquale; Craparo, Emanuela F; San Biagio, Pier L; Giammona, Gaetano; Di Carlo, Marta

2007-01-01

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. In this article, the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain stable materials able to condense RNA. Cationic SLN were produced by microemulsion using Compritol ATO 888 as matrix lipid, Pluronic F68 as tenside, and dimethyldioctadecylammonium bromide (DDAB) as cationic lipid. The resulting particles were approximately 100 nm in size and showed a highly positive surface charge (+41 mV) in water. Size and shape were further characterized by scanning electron microscopy (SEM) measurements. Moreover, we utilized the sea urchin as a model system to test their applicability on a living organism. To evaluate cationic SLN ability to complex the in vitro transcribed Paracentrotus lividus bep3 RNA, we utilized both light scattering and gel mobility experiments, and protection by nuclease degradation was also investigated. By microinjection experiment, we demonstrated that the nanoparticles do not inference with the viability of the P. lividus embryo and the complex nanoparticles-bep3 permits movement of the RNA during its localization in the egg, suggesting that it could be a suitable system for gene delivery. Taken together, all these results indicate that the cationic SNL are a good RNA carrier for gene transfer system and the sea urchin a simple and versatile candidate to test biological properties of nanotechnology devices.

Co-synthesis and drug delivery properties of mesoporous hydroxyapatite-silica composites.

PubMed

Zhao, Y F; Loo, S C J; Ma, J

2009-06-01

In this work, mesoporous hydroxyapatite-silica (HA-silica) composite materials with four different Si:Ca:P ratios were sol-gel derived through self-assembly using triblock copolymer Pluronics P123 as template. The composition and mesoporous structure formed were characterized by X-ray diffraction and electron microscopy. The XRD patterns indicated that the intensity of the HA phase becomes stronger as the Ca/Si ratio of the composite increases. From nitrogen gas analysis at 77 K, type IV isotherm plots for typical mesoporous materials were observed for all of the samples. However, the mesoporous structure of HA-silica tends to becomes less ordered as the Ca/Si ratio increases. Promising consistency between the pore sizes from the Barrett, Joyner and Halenda (BJH) method, Transmission Electron Microscopy (TEM) and Small Angle X-ray diffraction (SAXRD) was also observed. The formation mechanism of mesoporous HA-silica composites was proposed, where the interaction between the crystallization of HA and the surfactant liquid crystal determines the regularity of the meso-structure. In vitro drug loading and release studies showed that drug loading capacity is dependent on the pore volume of the sample, and the mesoporosity of the samples were responsible for the sustained release of drugs. In vitro cell culture of the samples showed promising biocompatibility where osteosarcoma cells were observed to grow favourably on the synthesized composites.

Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery

NASA Astrophysics Data System (ADS)

Mandal, Biman B.; Kundu, S. C.

2009-09-01

In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.

Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.

PubMed

Grisin, Tiphany; Bories, Christian; Bombardi, Martina; Loiseau, Philippe M; Rouffiac, Valérie; Solgadi, Audrey; Mallet, Jean-Maurice; Ponchel, Gilles; Bouchemal, Kawthar

2017-05-01

The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity. Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic ® F127 20 wt% hydrogel. The formulation completely cured C. albicans vaginal infection in mice and had a superior activity in comparison with AmB-DOC without addition of chitosan micro-platelets. In vitro studies showed that the platelets significantly enhance AmB-DOC antifungal activity since the IC 50 and the MIC 90 decrease 4.5 and 4.8-times. Calculation of fractional inhibitory concentration index (FICI = 0.198) showed that chitosan micro-platelets act in a synergistic way with AmB-DOC against C. albicans. No synergy is found between spherical nanoparticles composed poly(isobutylcyanoacrylate)/chitosan and AmB-DOC. These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.

Comparison of Sequential Drug Release in Vitro and in Vivo

PubMed Central

Sundararaj, Sharath C.; Al-Sabbagh, Mohanad; Rabek, Cheryl L.; Dziubla, Thomas D.; Thomas, Mark V.; Puleo, David A.

2015-01-01

Development of drug delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected “programming” achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Whereas many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, the present research demonstrated that sequential release of four drugs can be maintained following implantation. PMID:26111338

Addition of perfluorocarbons to alginate hydrogels significantly impacts molecular transport and fracture stress.

PubMed

White, Joseph C; Stoppel, Whitney L; Roberts, Susan C; Bhatia, Surita R

2013-02-01

Perfluorocarbons (PFCs) are used in biomaterial formulations to increase oxygen (O(2) ) tension and create a homogeneous O(2) environment in three-dimensional tissue constructs. It is unclear how PFCs affect mechanical and transport properties of the scaffold, which are critical for robustness, intracellular signaling, protein transport, and overall device efficacy. In this study, we investigate composite alginate hydrogels containing a perfluorooctyl bromide (PFOB) emulsion stabilized with Pluronic(®) F68 (F68). We demonstrate that PFC addition significantly affects biomaterial properties and performance. Solution and hydrogel mechanical properties and transport of representative hydrophilic (riboflavin), hydrophobic (methyl and ethyl paraben), and protein (bovine serum albumin, BSA) solutes were compared in alginate/F68 composite hydrogels with or without PFOB. Our results indicate that mechanical properties of the alginate/F68/PFOB hydrogels are not significantly affected under small strains, but a significant decrease fracture stress is observed. The effective diffusivity D(eff) of hydrophobic small molecules decreases with PFOB emulsion addition, yet the D(eff) of hydrophilic small molecules remained unaffected. For BSA, the D(eff) increased and the loading capacity decreased with PFOB emulsion addition. Thus, a trade-off between the desired increased O(2) supply provided by PFCs and the mechanical weakening and change in transport of cellular signals must be carefully considered in the design of biomaterials containing PFCs. Copyright © 2012 Wiley Periodicals, Inc.

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

PubMed Central

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles.

PubMed

Chen, Ying-Chen; Su, Chia-Yu; Jhan, Hua-Jun; Ho, Hsiu-O; Sheu, Ming-Thau

2015-01-01

To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic(®), Kolliphor(®), d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone(®), the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone(®) did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.

Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles

PubMed Central

Chen, Ying-Chen; Su, Chia-Yu; Jhan, Hua-Jun; Ho, Hsiu-O; Sheu, Ming-Thau

2015-01-01

To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic®, Kolliphor®, d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone®, the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone® did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect. PMID:26664117

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells.

PubMed

Rafael, Diana; Gener, Petra; Andrade, Fernanda; Seras-Franzoso, Joaquin; Montero, Sara; Fernández, Yolanda; Hidalgo, Manuel; Arango, Diego; Sayós, Joan; Florindo, Helena F; Abasolo, Ibane; Schwartz, Simó; Videira, Mafalda

2018-11-01

Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic ® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather the requirements for an efficient and safe transport of siRNA in terms of its physicochemical characteristics, internalization capacity, toxicity profile and silencing efficacy. PM were loaded with a siRNA against AKT2, an important oncogene involved in breast cancer tumorigenesis, with a special role in CSC malignancy. Efficacy of siAKT2-PM was validated in CSC isolated from two breast cancer cell lines: MCF-7 and Triple Negative MDA-MB-231 corresponding to an aggressive subtype of breast cancer. In both cases, we observed significant reduction on cell invasion capacity and strong inhibition of mammosphere formation after treatment. These results prompt AKT2 inhibition as a powerful therapeutic target against CSC and pave the way to the appearance of more effective nanomedicine-based gene therapies aimed to prevent CSC-related tumor recurrence.

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core-Shell, Multilayer, and Gradient Concentration Profiles.

PubMed

Haring, Alexander P; Tong, Yuxin; Halper, Justin; Johnson, Blake N

2018-06-10

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery.

PubMed

Mandal, Biman B; Kundu, S C

2009-09-02

In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.

Electrochemical studies of mesoporous and copper-modified mesoporous TiO2 -anode material

NASA Astrophysics Data System (ADS)

Ajay Kumar, R.; Venkateswara Rao, A.; Rajesh, Ch.

2018-05-01

Herein, we developed a method to synthesize highly ordered mesoporous TiO2 (MT) and copper-modified M- TiO2 (CMT) with a high surface area by the hydrothermal method using Pluronic P-123 as a surfactant at 150 ° C. CMT with different copper concentrations (0.1, 0.2 and 0.3%) was synthesized. The structural characterization studies revealed that MT and CMT particles are in anatase phase. The average particle size was found to be 24± 0.8 nm for MT and that of CMT was 25± 0.6 , 27± 0.4 and 28± 0.3 nm, respectively. The presence of ordered spherical MT and CMT particles with uniform size distribution was confirmed by performing morphological studies using FE-SEM. Optical absorption studies indicate the presence of copper because of the red shift in the band gap and also a broad peak around 800nm when compared with MT. EIS studies point out an increase in conductivity from MT through 0.3% CMT by a decrease in the charge transfer resistance. Further, charge-discharge studies were carried on this material at room temperature for lithium-ion battery applications. CMT with 0.3% copper showed high initial discharge capacity and better cyclability. The results indicate that this material can act as a promising negative electrode.

Development and characterization of acrylated palm oil nanoparticles using ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tajau, Rida; Yunus, Wan Md Zin Wan; Dahlan, Khairul Zaman Mohd

2012-11-27

In this study, the utilization of radiation crosslinking methods which are known as intermolecular and intramolecular crosslinking for the formation of nanoparticles of Acrylated Palm Oil (APO) in the microemulsion system that also consists of Pluronic F-127 (PF-127) surfactant was demonstrated. This microemulsion system was subjected to the ionizing radiation i.e. gamma irradiation at different doses to form the crosslinked APO nanoparticles. The effects of radiation doses on the size of APO nanoparticles were investigated using the Dynamic Light Scattering (DLS) method and their images were viewed using the Transmission Electron Microcrospy (TEM). The Fourier Transform Infra-Red (FTIR) spectroscopy wasmore » used to characterize the chemical structure and the crosslinking conversion of carbon-carbon double bond (-C = C-) of the APO nanoparticles after irradiation. As a result, the size of the APO nanoparticle decreased when the irradiation dose increased. Reduce in size might be due to the effect of intramolecular crosslinking reaction of the APO nanoparticles during irradiation process. Meanwhile, the intramolecular -C C- crosslinking conversion percentage was increased at doses below 1kGy before decreasing at the higher dose that might due to the intermolecular crosslinking of the macromolecules. This study showed that radiation crosslinking methods of polymerization and crosslinking in the microemulsion were found to be promising for the synthesis of nanoparticles.« less

Formulation and Stabilization of Francisella tularensis Live Vaccine Strain

PubMed Central

OHTAKE, SATOSHI; MARTIN, RUSSELL A.; SAXENA, ATUL; LECHUGA-BALLESTEROS, DAVID; SANTIAGO, ARACELI E; BARRY, EILEEN M.; TRUONG-LE, VU

2012-01-01

Francisella tularensis live vaccine strain (F. tularensis LVS), a promising vaccine candidate for protection against F. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. Our preliminary data show that F. tularensis LVS can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. The process was conducted under mild drying conditions, which resulted in a good titer retention following processing. The inclusion of osmolytes in the growth media resulted in an acceleration of growth kinetics, although no change in osmotolerance was observed. The optimized F. tularensis formulation, which contained trehalose, gelatin, and Pluronic F68 demonstrated stability for approximately 1.5 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1 log10 colony forming unit) and for 12 weeks at 25°C. At refrigerator storage condition (4°C), stabilized F. tularensis LVS vaccine exhibited no activity loss for at least 12 weeks. This stabilization method utilizes conventional freeze dryers and pharmaceutically approved stabilizers, and thus can be readily implemented at many manufacturing sites for large-scale production of stabilized vaccines. The improved heat stability of the F. tularensis LVS could mitigate risks of vaccine potency loss during long-term storage, shipping, and distribution. PMID:21491457

Sulfacetamide loaded Eudragit® RL100 nanosuspension with potential for ocular delivery.

PubMed

Mandal, Bivash; Alexander, Kenneth S; Riga, Alan T

2010-01-01

Polymeric nanosuspension was prepared from an inert polymer resin (Eudragit® RL100) with the aim of improving the availability of sulfacetamide at the intraocular level to combat bacterial infections. Nanosuspensions were prepared by the solvent displacement method using acetone and Pluronic® F108 solution. Drug to polymer ratio was selected as formulation variable. Characterization of the nanosupension was performed by measuring particle size, zeta potential, Fourier Transform infrared spectra (FTIR), Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD), drug entrapment efficiency and in vitro release. In addition, freeze drying, redispersibility and short term stability study at room temperature and at 4(0)C were performed. Spherical, uniform particles (size below 500 nm) with positive zeta potential were obtained. No significant chemical interactions between drug and polymer were observed in the solid state characterization of the freeze dried nanosuspension (FDN). Drug entrapment efficiency of the selected batch was increased by changing the pH of the external phase and addition of polymethyl methacrylate in the formulation. The prepared nanosuspension exhibited good stability after storage at room temperature and at 4(0)C. Sucrose and Mannitol were used as cryoprotectants and exhibited good water redispersibility of the FDN. The results indicate that the formulation of sulfacetamide in Eudragit® RL100 nanosuspension could be utilized as potential delivery system for treating ocular bacterial infections.

Stabilizing nanocellulose-nonionic surfactant composite foams by delayed Ca-induced gelation.

PubMed

Gordeyeva, Korneliya S; Fall, Andreas B; Hall, Stephen; Wicklein, Bernd; Bergström, Lennart

2016-06-15

Aggregation of dispersed rod-like particles like nanocellulose can improve the strength and rigidity of percolated networks but may also have a detrimental effect on the foamability. However, it should be possible to improve the strength of nanocellulose foams by multivalent ion-induced aggregation if the aggregation occurs after the foam has been formed. Lightweight and highly porous foams based on TEMPO-mediated oxidized cellulose nanofibrils (CNF) were formulated with the addition of a non-ionic surfactant, pluronic P123, and CaCO3 nanoparticles. Foam volume measurements show that addition of the non-ionic surfactant generates wet CNF/P123 foams with a high foamability. Foam bubble size studies show that delayed Ca-induced aggregation of CNF by gluconic acid-triggered dissolution of the CaCO3 nanoparticles significantly improves the long-term stability of the wet composite foams. Drying the Ca-reinforced foam at 60 °C results in a moderate shrinkage and electron microscopy and X-ray tomography studies show that the pores became slightly oblate after drying but the overall microstructure and pore/foam bubble size distribution is preserved after drying. The elastic modulus (0.9-1.4 MPa) of Ca-reinforced composite foams with a density of 9-15 kg/m(3) is significantly higher than commercially available polyurethane foams used for thermal insulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo

PubMed Central

Graham, Hannah K.; Nagy, Nandor; Belkind-Gerson, Jaime; Mattheolabakis, George; Amiji, Mansoor M.; Goldstein, Allan M.

2016-01-01

Cell therapy offers an innovative approach for treating enteric neuropathies. Postnatal gut-derived enteric neural stem/progenitor cells (ENSCs) represent a potential autologous source, but have a limited capacity for proliferation and neuronal differentiation. Since serotonin (5-HT) promotes enteric neuronal growth during embryonic development, we hypothesized that serotonin receptor agonism would augment growth of neurons from transplanted ENSCs. Postnatal ENSCs were isolated from 2-4 week-old mouse colon and cultured with 5-HT4 receptor agonist (RS67506)-loaded liposomal nanoparticles. ENSCs were co-cultured with mouse colon explants in the presence of RS67506-loaded (n=3) or empty nanoparticles (n=3). ENSCs were also transplanted into mouse rectum in vivo with RS67506-loaded (n=8) or blank nanoparticles (n=4) confined in a thermosensitive hydrogel, Pluronic F-127. Neuronal density and proliferation were analyzed immunohistochemically. Cultured ENSCs gave rise to significantly more neurons in the presence of RS67506-loaded nanoparticles. Similarly, colon explants had significantly increased neuronal density when RS67506-loaded nanoparticles were present. Finally, following in vivo cell delivery, co-transplantation of ENSCs with 5-HT4 receptor agonist-loaded nanoparticles led to significantly increased neuronal density and proliferation. We conclude that optimization of postnatal ENSCs can support their use in cell-based therapies for neurointestinal diseases. PMID:26922325

In vivo evaluation of hybrid patches composed of PLA based copolymers and collagen/chondroitin sulfate for ligament tissue regeneration.

PubMed

Pinese, Coline; Gagnieu, Christian; Nottelet, Benjamin; Rondot-Couzin, Capucine; Hunger, Sylvie; Coudane, Jean; Garric, Xavier

2017-10-01

Biomaterials for soft tissues regeneration should exhibit sufficient mechanical strength, demonstrating a mechanical behavior similar to natural tissues and should also promote tissues ingrowth. This study was aimed at developing new hybrid patches for ligament tissue regeneration by synergistic incorporation of a knitted structure of degradable polymer fibers to provide mechanical strength and of a biomimetic matrix to help injured tissues regeneration. PLA- Pluronic ® (PLA-P) and PLA-Tetronic ® (PLA-T) new copolymers were shaped as knitted patches and were associated with collagen I (Coll) and collagen I/chondroitine-sulfate (Coll CS) 3-dimensional matrices. In vitro study using ligamentocytes showed the beneficial effects of CS on ligamentocytes proliferation. Hybrid patches were then subcutaneously implanted in rats for 4 and 12 weeks. Despite degradation, patches retained strength to answer the mechanical physiological needs. Tissue integration capacity was assessed with histological studies. We showed that copolymers, associated with collagen and chondroitin sulfate sponge, exhibited very good tissue integration and allowed neotissue synthesis after 12 weeks in vivo. To conclude, PLA-P/CollCS and PLA-T/CollCS hybrid patches in terms of structure and composition give good hopes for tendon and ligament regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1778-1788, 2017. © 2016 Wiley Periodicals, Inc.

Thin-film composite materials as a dielectric layer for flexible metal-insulator-metal capacitors.

PubMed

Tiwari, Jitendra N; Meena, Jagan Singh; Wu, Chung-Shu; Tiwari, Rajanish N; Chu, Min-Ching; Chang, Feng-Chih; Ko, Fu-Hsiang

2010-09-24

A new organic-organic nanoscale composite thin-film (NCTF) dielectric has been synthesized by solution deposition of 1-bromoadamantane and triblock copolymer (Pluronic P123, BASF, EO20-PO70-EO20), in which the precursor solution has been achieved with organic additives. We have used a sol-gel process to make a metal-insulator-metal capacitor (MIM) comprising a nanoscale (10 nm-thick) thin-film on a flexible polyimide (PI) substrate at room temperature. Scanning electron microscope and atomic force microscope revealed that the deposited NCTFs were crack-free, uniform, highly resistant to moisture absorption, and well adhered on the Au-Cr/PI. The electrical properties of 1-bromoadamantane-P123 NCTF were characterized by dielectric constant, capacitance, and leakage current measurements. The 1-bromoadamantane-P123 NCTF on the PI substrate showed a low leakage current density of 5.5 x 10(-11) A cm(-2) and good capacitance of 2.4 fF at 1 MHz. In addition, the calculated dielectric constant of 1-bromoadamantane-P123 NCTF was 1.9, making them suitable candidates for use in future flexible electronic devices as a stable intermetal dielectric. The electrical insulating properties of 1-bromoadamantane-P123 NCTF have been improved due to the optimized dipole moments of the van der Waals interactions.

Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

PubMed

Kant, Vinay; Kumar, Dinesh; Kumar, Dhirendra; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

2015-05-01

Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toxicological Profiling of Highly Purified Single-Walled Carbon Nanotubes with Different Lengths in the Rodent Lung and Escherichia Coli.

PubMed

Wang, Xiang; Lee, Jae-Hyeok; Li, Ruibin; Liao, Yu-Pei; Kang, Joohoon; Chang, Chong Hyun; Guiney, Linda M; Mirshafiee, Vahid; Li, Linjiang; Lu, Jianqin; Xia, Tian; Hersam, Mark C; Nel, André E

2018-06-01

Carbon nanotubes (CNTs) exhibit a number of physicochemical properties that contribute to adverse biological outcomes. However, it is difficult to define the independent contribution of individual properties without purified materials. A library of highly purified single-walled carbon nanotubes (SWCNTs) of different lengths is prepared from the same base material by density gradient ultracentrifugation, designated as short (318 nm), medium (789 nm), and long (1215 nm) SWCNTs. In vitro screening shows length-dependent interleukin-1β (IL-1β) production, in order of long > medium > short. However, there are no differences in transforming growth factor-β1 production in BEAS-2B cells. Oropharyngeal aspiration shows that all the SWCNTs induce profibrogenic effects in mouse lung at 21 d postexposure, but there are no differences between tube lengths. In contrast, these SWCNTs demonstrate length-dependent antibacterial effects on Escherichia coli, with the long SWCNT exerting stronger effects than the medium or short tubes. These effects are reduced by Pluronic F108 coating or supplementing with glucose. The data show length-dependent effects on proinflammatory response in macrophage cell line and antibacterial effects, but not on collagen deposition in the lung. These data demonstrate that over the length scale tested, the biological response to highly purified SWCNTs is dependent on the complexity of the nano/bio interface. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers.

PubMed

Li, Fang; Weng, Yan; Wang, Lihui; He, Haibing; Yang, Jingyu; Tang, Xing

2010-06-30

Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides. 2010 Elsevier B.V. All rights reserved.

Preparation, characterization, pharmacokinetics and tissue distribution of solid lipid nanoparticles loaded with tetrandrine.

PubMed

Li, Su; Ji, Zhaoshuai; Zou, Meijuan; Nie, Xin; Shi, Yijie; Cheng, Gang

2011-09-01

Tetrandrine (TET) is a poorly water-soluble bisbenzylisoquinoline alkaloid. In this study, TET solid lipid nanoparticles (SLNs) were prepared by a melt-emulsification and ultrasonication technique. Precirol(®) ATO 5, glyceryl monostearate, and stearic acid were used as the lipid matrix for the SLNs, while Lipoid E80, Pluronic F68, and sodium deoxycholate were used as emulsifying and stabilizing agents. The physicochemical characteristics of the TET-SLNs were investigated when it was found that the mean particle size and zeta potential of the TET-SLNs were 134 ± 1.3 nm and -53.8 ± 1.7 mV, respectively, and the entrapment efficiency (EE) was 89.57% ± 0.39%. Differential scanning calorimetry indicated that TET was in an amorphous state in SLNs. TET-SLNs exhibited a higher release rate at a lower pH and a lower release rate at a higher pH. The release pattern of the TET-SLNs followed the Weibull model. The pharmacokinetics of TET-SLNs after intravenous administration to male rats was studied. TET-SLN resulted in a higher plasma concentration and lower clearance. The biodistribution study indicated that TET-SLN showed a high uptake in reticuloendothelial system organs. In conclusion, TET-SLNs with a small particle size, and high EE, can be produced by the method described in this study. The SLN system is a promising approach for the intravenous delivery of tetrandrine.

Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam.

PubMed

Abbas, Haidy; Refai, Hanan; El Sayed, Nesrine

2018-04-14

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol ® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Physicochemical perspectives (aggregation, structure and dynamics) of interaction between pluronic (L31) and surfactant (SDS).

PubMed

Prameela, G K S; Phani Kumar, B V N; Pan, A; Aswal, V K; Subramanian, J; Mandal, A B; Moulik, S P

2015-11-11

The influence of the water soluble non-ionic tri-block copolymer PEO-PPO-PEO [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] i.e., E2P16E2 (L31) on the microstructure and self-aggregation dynamics of the anionic surfactant sodium dodecylsulfate (SDS) in aqueous solution was investigated using cloud point (CP), isothermal titration calorimetry (ITC), high resolution nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and small-angle neutron scattering (SANS) measurements. CP provided the thermodynamic information on the Gibbs free energy, enthalpy, entropy and heat capacity changes pertaining to the phase separation of the system at elevated temperature. The ITC and NMR self-diffusion measurements helped to understand the nature of the binding isotherms of SDS in the presence of L31 in terms of the formation of mixed aggregates and free SDS micelles in solution. EPR analysis provided the micro-viscosity of the spin probe 5-DSA in terms of rotational correlation time. The SANS study indicated the presence of prolate ellipsoidal mixed aggregates, whose size increased with the increasing addition of L31. At a large [L31], SANS also revealed the progressive decreasing size of the ellipsoidal mixed aggregates of SDS-L31 into nearly globular forms with the increasing SDS addition. Wrapping of the spherical SDS micelles by L31 was also corroborated from (13)C NMR and SANS measurements.

Robust Mesoporous CoMo/γ-Al2O3 Catalysts from Cyclodextrin-Based Supramolecular Assemblies for Hydrothermal Processing of Microalgae: Effect of the Preparation Method.

PubMed

Bleta, Rudina; Schiavo, Benedetto; Corsaro, Natale; Costa, Paula; Giaconia, Alberto; Interrante, Leonardo; Monflier, Eric; Pipitone, Giuseppe; Ponchel, Anne; Sau, Salvatore; Scialdone, Onofrio; Tilloy, Sébastien; Galia, Alessandro

2018-04-18

Hydrothermal liquefaction (HTL) is a promising technology for the production of biocrude oil from microalgae. Although this catalyst-free technology is efficient under high-temperature and high-pressure conditions, the biocrude yield and quality can be further improved by using heterogeneous catalysts. The design of robust catalysts that preserve their performance under hydrothermal conditions will be therefore very important in the development of biorefinery technologies. In this work, we describe two different synthetic routes (i.e., impregnation and cyclodextrin-assisted one-pot colloidal approach), for the preparation in aqueous phase of six high surface area CoMo/γ-Al 2 O 3 catalysts. Catalytic tests performed on the HTL of Nannochloropsis gaditana microalga indicate that solids prepared by the one-pot colloidal approach show higher hydrothermal stability and enhanced biocrude yield with respect to the catalyst-free test. The positive effect of the substitution of the block copolymer Tetronic T90R4 for Pluronic F127 in the preparation procedure was evidenced by diffuse reflectance UV-visible spectroscopy, X-ray diffraction, N 2 -adsorption-desorption, and H 2 -temperature-programmed reduction measurements and confirmed by the higher quality of the obtained biocrude, which exhibited lower oxygen content and higher-energy recovery equal to 62.5% of the initial biomass.

Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen.

PubMed

Yen, Yu-Hsiu; Pu, Chi-Ming; Liu, Chen-Wei; Chen, Ya-Chun; Chen, Yu-Chen; Liang, Chan-Jung; Hsieh, Jung-Hsien; Huang, Hui-Fu; Chen, Yuh-Lien

2018-04-16

Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory, and antioxidative effects, but its effects on wound healing are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by haematoxylin and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear factor kappa B signalling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Complementary use of flow and sedimentation field-flow fractionation techniques for size characterizing biodegradable poly(lactic acid) nanospheres

PubMed Central

Contado, Catia; Dalpiaz, Alessandro; Leo, Eliana; Zborowski, Maciej; Williams, P. Stephen

2009-01-01

Poly(lactic acid) nanoparticles were synthesized using a modified evaporation method, testing two different surfactants (sodium cholate and Pluronic F68) for the process. During their formulation the prodrug 5′-octanoyl-CPA (Oct-CPA) of the antiischemic N6-cyclopentyladenosine (CPA) was encapsulated. Three different purification methods were compared with respect to the influence of surfactant on the size characteristics of the final nanoparticle product. Flow and sedimentation field-flow fractionation techniques (FlFFF and SdFFF, respectively) were used to size characterize the five poly(lactic acid) particle samples. Two different combinations of carrier solution (mobile phase) were employed in the FlFFF analyses, while a solution of poly(vinyl alcohol) was used as mobile phase for the SdFFF runs. The separation performances of the two techniques were compared and the particle size distributions, derived from the fractograms, were interpreted with the support of observations by scanning electron microscopy. Some critical aspects, such as the carrier choice and the channel thickness determination for the FlFFF, have been investigated. This is the first comprehensive comparison of the two FFF techniques for characterizing non standard particulate materials. The two FFF techniques proved to be complementary and gave good, congruent and very useful information on the size distributions of the five poly(lactic acid) particle samples. PMID:17482199

Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.

PubMed

Li, Yongqiang; Abbaspour, Mohammadreza R; Grootendorst, Paul V; Rauth, Andrew M; Wu, Xiao Yu

2015-08-01

This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural lipids-based NLC containing lidocaine: from pre-formulation to in vivo studies.

PubMed

Ribeiro, Lígia N M; Breitkreitz, Márcia C; Guilherme, Viviane A; da Silva, Gustavo H R; Couto, Verônica M; Castro, Simone R; de Paula, Bárbara O; Machado, Daisy; de Paula, Eneida

2017-08-30

In a nanotechnological approach we have investigated the use of natural lipids in the preparation of nanostructured lipid carriers (NLC). Three different NLC composed of copaiba oil and beeswax, sweet almond oil and shea butter, and sesame oil and cocoa butter as structural matrices were optimized using factorial analysis; Pluronic® 68 and lidocaine (LDC) were used as the colloidal stabilizer and model encapsulated drug, respectively. The optimal formulations were characterized by different techniques (IR-ATR, DSC, and TEM), and their safety and efficacy were also tested. These nanocarriers were able to upload high amounts of the anesthetic with a sustained in vitro release profile for 24h. The physicochemical stability in terms of size (nm), PDI, zeta potential (mV), pH, nanoparticle concentration (particles/mL), and visual inspection was followed during 12months of storage at 25°C. The formulations exhibited excellent structural properties and stability. They proved to be nontoxic in vitro (cell viability tests with Balb/c 3T3 fibroblasts) and significantly improved the in vivo effects of LDC, over the heart rate of zebra fish larvae and in the blockage of sciatic nerve in mice. The results from this study support that the proper combination of natural excipients is promising in DDS, taking advantage of the biocompatibility, low cost, and diversity of lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

Pluronic based β-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type C disease

NASA Astrophysics Data System (ADS)

Collins, Christopher J.; Loren, Bradley P.; Alam, Md Suhail; Mondjinou, Yawo; Skulsky, Joseph L.; Chaplain, Cheyenne R.; Haldar, Kasturi; Thompson, David H.

2017-04-01

Niemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by disruption of normal cholesterol trafficking within the cells of the body. There are no FDA approved treatments available for NPC patients. Recently, the cycloheptaglucoside 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has shown efficacy as a potential NPC therapeutic by extending lifetime in NPC mice, delaying neurodegeneration, and decreasing visceral and neurological cholesterol burden. Although promising, systemic HP-β-CD treatment is limited by a pharmacokinetic profile characterized by rapid loss through renal filtration. To address these shortcomings, we sought to design a family of HP-β-CD pro-drug delivery vehicles, known as polyrotaxanes (PR), capable of increasing the efficacy of a given injected dose by improving both pharmacokinetic profile and bioavailability of the HP-β-CD agent. PR can effectively diminish the cholesterol pool within the liver, spleen, and kidney at molar concentrations 10-to-100-fold lower than monomeric HP-β-CD. In addition to this proof-of-concept, use of PR scaffolds with differing physiochemical properties reveal structure-activity relationships in which PR characteristics, including hydrophobicity, threading efficiency and surface charge, were found to both decisively and subtly effect therapeutic efficacy. PR scaffolds exhibit absorption, pharmacokinetics, and biodistribution patterns that are significantly altered from monomeric HP-β-CD. In all, PR scaffolds hold great promise as potential treatments for visceral disease in NPC patients.

Effect of different types of surfactants on the microstructure of methyltrimethoxysilane-derived silica aerogels: A combined experimental and computational approach.

PubMed

Vareda, João P; Maximiano, Pedro; Cunha, Luís P; Ferreira, André F; Simões, Pedro N; Durães, Luísa

2018-02-15

Surfactants interfere with sol-gel particle/pore growth, influencing the structure and properties of silica aerogels. Their ability to induce microscopic changes in the aerogel's structure may be useful to improve/control the thermal insulation performance of aerogels. The influence of different types of surfactants (anionic, cationic and non-ionic) on the microstructural arrangement and macroscopic properties of methyltrimethoxysilane (MTMS)-based aerogels was evaluated for the first time, using an experimental and computational comparative approach. Molecular dynamics simulations were performed based on two representative silica molecular structures derived from MTMS, while the experimentally-obtained silica aerogels were characterized in terms of chemical/structural/mechanical/thermal insulation properties. The use of both hexadecyltrimethylammonium bromide (CTAB) and sodium dodecylsulfate (SDS) led to a decrease in bulk density, thermal conductivity and average pore size of the aerogels, with notorious increase of their flexibility. The observed changes were due to microstructural arrangements, as evidenced by scanning electron microscopy (SEM). However, the non-ionic surfactant, Pluronic F-127, did not have a positive impact on the desired properties. Globally, the simulation results support the experimental findings, suggesting differentiated microstructural changes induced by the use of cationic or anionic surfactants. The addition of CTAB and SDS generally resulted in smaller or larger silica aggregates, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Fluorenyl benzothiadiazole and benzoselenadiazole near-IR fluorescent probes for two-photon fluorescence imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Belfield, Kevin D.; Yao, Sheng; Kim, Bosung; Yue, Xiling

2016-03-01

Imaging biological samples with two-photon fluorescence (2PF) microscopy has the unique advantage of resulting high contrast 3D resolution subcellular image that can reach up to several millimeters depth. 2PF probes that absorb and emit at near IR region need to be developed. Two-photon excitation (2PE) wavelengths are less concerned as 2PE uses wavelengths doubles the absorption wavelength of the probe, which means 2PE wavelengths for probes even with absorption at visible wavelength will fall into NIR region. Therefore, probes that fluoresce at near IR region with high quantum yields are needed. A series of dyes based on 5-thienyl-2, 1, 3-benzothiadiazole and 5-thienyl-2, 1, 3-benzoselenadiazole core were synthesized as near infrared two-photon fluorophores. Fluorescence maxima wavelengths as long as 714 nm and fluorescence quantum yields as high as 0.67 were achieved. The fluorescence quantum yields of the dyes were nearly constant, regardless of solvents polarity. These diazoles exhibited large Stokes shift (<114nm), high two-photon absorption cross sections (up to 2,800 GM), and high two-photon fluorescence figure of merit (FM , 1.04×10-2 GM). Cells incubated on a 3D scaffold with one of the new probes (encapsulated in Pluronic micelles) exhibited bright fluorescence, enabling 3D two-photon fluorescence imaging to a depth of 100 µm.

Mg doped Li2FeSiO4/C nanocomposites synthesized by the solvothermal method for lithium ion batteries.

PubMed

Kumar, Ajay; Jayakumar, O D; Jagannath; Bashiri, Parisa; Nazri, G A; Naik, Vaman M; Naik, Ratna

2017-10-14

A series of porous Li 2 Fe 1-x Mg x SiO 4 /C (x = 0, 0.01, 0.02, 0.04) nanocomposites (LFS/C, 1Mg-LFS/C, 2Mg-LFS and 4Mg-LFS/C) have been synthesized via a solvo-thermal method using the Pluronic P123 polymer as an in situ carbon source. Rietveld refinement of the X-ray diffraction data of Li 2 Fe 1-x Mg x SiO 4 /C composites confirms the formation of the monoclinic P2 1 structure of Li 2 FeSiO 4 . The addition of Mg facilitates the growth of impurity-free Li 2 FeSiO 4 with increased crystallinity and particle size. Despite having the same percentage of carbon content (∼15 wt%) in all the samples, the 1Mg-LFS/C nanocomposite delivered the highest initial discharge capacity of 278 mA h g -1 (∼84% of the theoretical capacity) at the C/30 rate and also exhibited the best rate capability and cycle stability (94% retention after 100 charge-discharge cycles at 1C). This is attributed to its large surface area with a narrow pore size distribution and a lower charge transfer resistance with enhanced Li-ion diffusion coefficient compared to other nanocomposites.

Polymeric mixed micelles loaded mitoxantrone for overcoming multidrug resistance in breast cancer via photodynamic therapy

PubMed Central

Zhao, Yiqiao; Yu, Hua; Zhou, Haiyu; Chen, Meiwan

2017-01-01

Mitoxantrone (MIT) is an anticancer agent with photosensitive properties that is commonly used in various cancers. Multidrug resistance (MDR) effect has been an obstacle to using MIT for cancer therapy. Photochemical internalization, on account of photodynamic therapy, has been applied to improve the therapeutic effect of cancers with MDR effect. In this study, an MIT-poly(ε-caprolactone)-pluronic F68-poly(ε-caprolactone)/poly(d,l-lactide-co-glycolide)–poly(ethylene glycol)–poly(d,l-lactide-co-glycolide) (MIT-PFP/PPP) mixed micelles system was applied to reverse the effect of MDR in MCF-7/ADR cells via photochemical reaction when exposed to near-infrared light. MIT-PFP/PPP mixed micelles showed effective interaction with near-infrared light at the wavelength of 660 nm and exerted great cytotoxicity in MCF-7/ADR cells with irradiation. Furthermore, MIT-PFP/PPP mixed micelles could improve reactive oxygen species (ROS) levels, decrease P-glycoprotein activity, and increase the cellular uptake of drugs with improved intracellular drug concentrations, which induced cell apoptosis in MCF-7/ADR cells under irradiation, despite MDR effect, as indicated by the increased level of cleaved poly ADP-ribose polymerase. These findings suggested that MIT-PFP/PPP mixed micelles may become a promising strategy to effectively reverse the MDR effect via photodynamic therapy in breast cancer. PMID:28919756

Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.

PubMed

Schachner, Thomas; Oberhuber, Alexander; Zou, Yping; Tzankov, Alexandar; Ott, Harald; Laufer, Günther; Bonatti, Johannes

2005-02-01

Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model. C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 microg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) microm at 4 weeks postoperatively. In 200 microg rapamycin treated grafts the neointimal thickness was 17 (5-55) microm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls. We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.

Pluronic based β-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type C disease.

PubMed

Collins, Christopher J; Loren, Bradley P; Alam, Md Suhail; Mondjinou, Yawo; Skulsky, Joseph L; Chaplain, Cheyenne R; Haldar, Kasturi; Thompson, David H

2017-04-28

Niemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by disruption of normal cholesterol trafficking within the cells of the body. There are no FDA approved treatments available for NPC patients. Recently, the cycloheptaglucoside 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has shown efficacy as a potential NPC therapeutic by extending lifetime in NPC mice, delaying neurodegeneration, and decreasing visceral and neurological cholesterol burden. Although promising, systemic HP-β-CD treatment is limited by a pharmacokinetic profile characterized by rapid loss through renal filtration. To address these shortcomings, we sought to design a family of HP-β-CD pro-drug delivery vehicles, known as polyrotaxanes (PR), capable of increasing the efficacy of a given injected dose by improving both pharmacokinetic profile and bioavailability of the HP-β-CD agent. PR can effectively diminish the cholesterol pool within the liver, spleen, and kidney at molar concentrations 10-to-100-fold lower than monomeric HP-β-CD. In addition to this proof-of-concept, use of PR scaffolds with differing physiochemical properties reveal structure-activity relationships in which PR characteristics, including hydrophobicity, threading efficiency and surface charge, were found to both decisively and subtly effect therapeutic efficacy. PR scaffolds exhibit absorption, pharmacokinetics, and biodistribution patterns that are significantly altered from monomeric HP-β-CD. In all, PR scaffolds hold great promise as potential treatments for visceral disease in NPC patients.

A comparative study of vitamin E TPGS/HPMC supersaturated system and other solubilizer/polymer combinations to enhance the permeability of a poorly soluble drug through the skin.

PubMed

Ghosh, Indrajit; Michniak-Kohn, Bozena

2012-11-01

In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across skin, because the concentration of the drug dissolved in the matrix has to be high in order to maintain zero order release kinetics of the drug. In case of poorly soluble drugs, due to thermodynamic challenges, there is a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of vitamin E TPGS/HPMC supersaturated solution and other solubilizer/polymer systems to improve the solubility of the drug and inhibit crystal growth in the transdermal formulation. Effect of several solubilizers, for example, Pluronic F-127, vitamin E TPGS and co-solvent, for example, propylene glycol (PG) were studied on the supersaturated systems of ibuprofen as model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC 3 cps) and polyvinylpyrrolidone (PVP K-30) were examined to evaluate their crystal inhibitory effects. Different analytical tools were used in this study to detect the growth of crystals in the systems. Vitamin E TPGS and HPMC 3 cps formulation produced the highest permeation rate of the drug as compared to other systems. In addition, the onset of crystallization time was shown to be longer with this formulation as compared to other solubilizer/polymer combinations.

Design and characterization of submicron formulation for a poorly soluble drug: the effect of Vitamin E TPGS and other solubilizers on skin permeability enhancement.

PubMed

Ghosh, Indrajit; Michniak-Kohn, Bozena

2012-09-15

In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems, however, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of drug crystals at the submicron/nano range in presence of different solubilizers to improve the permeation rate. Effect of several solubilizers, e.g. Pluronic F-127, Vitamin E TPGS, propylene glycol were studied on the submicron suspension systems of ibuprofen as a model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined to evaluate their crystal inhibitory effects on particle growth of the drug compound at submicron range. The overall permeation enhancement process through the skin seems to be influenced by the presence of solubilizers and also the presence of submicron drug crystal. The most promising stable formulation was developed with Vitamin E TPGS+HPMC submicron suspension, which produced higher permeation rate compared to other vehicles. Copyright © 2012 Elsevier B.V. All rights reserved.

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

PubMed

Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

2013-01-01

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

Restenosis Inhibition and Re-differentiation of TGFβ/Smad3-activated Smooth Muscle Cells by Resveratrol

PubMed Central

Zhu, Yichen; Takayama, Toshio; Wang, Bowen; Kent, Alycia; Zhang, Mengxue; Binder, Bernard Y.K.; Urabe, Go; Shi, Yatao; DiRenzo, Daniel; Goel, Shakti A.; Zhou, Yifan; Little, Christopher; Roenneburg, Drew A.; Shi, Xu Dong; Li, Lingjun; Murphy, William L.; Kent, K. Craig; Ke, Jianjuan; Guo, Lian-Wang

2017-01-01

To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. In a rat carotid injury model, periadventitial delivery of resveratrol either via Pluronic gel (2-week), or polymer sheath (3-month), effectively reduced IH without causing endothelium impairment and vessel shrinkage. In an in vitro model, primary smooth muscle cells (SMCs) were stimulated with elevated transforming growth factor (TGFβ) and its signaling protein Smad3, known contributors to IH. TGFβ/Smad3 up-regulated Kruppel-like factor (KLF5) protein, and SMC de-differentiation which was reversed by KLF5 siRNA. Furthermore, TGFβ/Smad3-stimulated KLF5 production and SMC de-differentiation were blocked by resveratrol via its inhibition of the Akt-mTOR pathway. Concordantly, resveratrol attenuated Akt phosphorylation in injured arteries. Taken together, periadventitial delivery of resveratrol produces durable inhibition of all three pro-restenotic pathologies — a rare feat among existing anti-restenotic methods. Our study suggests a potential anti-restenotic modality of resveratrol application suitable for open surgery. PMID:28165488

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

PubMed Central

Capretto, Lorenzo; Mazzitelli, Stefania; Brognara, Eleonora; Lampronti, Ilaria; Carugo, Dario; Hill, Martyn; Zhang, Xunli; Gambari, Roberto; Nastruzzi, Claudio

2012-01-01

This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH), based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of β-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying β-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for β-thalassemia. PMID:22287841

L-Cysteine conjugated poly L-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissues in vivo.

PubMed

Mishra, Brijeshkunvar J; Kaul, Ankur; Trivedi, Piyush

2015-02-01

Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

Preparation of oridonin-loaded solid lipid nanoparticles and studies on them in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhang, Dianrui; Tan, Tianwei; Gao, Lei

2006-12-01

Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F68 in our studies to overcome this problem. Emulsion evaporation-solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15-35 nm and mean zeta potential -45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.

Towards a fully synthetic substitute of alginate: optimization of a thermal gelation/chemical cross-linking scheme ("tandem" gelation) for the production of beads and liquid-core capsules.

PubMed

Cellesi, F; Weber, W; Fussenegger, M; Hubbell, J A; Tirelli, N

2004-12-20

Fully synthetic polymers were used for the preparation of hydrogel beads and capsules, in a processing scheme that, originally designed for calcium alginate, was adapted to a "tandem" process, that is the combination a physical gelation with a chemical cross-linking. The polymers feature a Tetronic backbone (tetra armed Pluronics), which exhibits a reverse thermal gelation in water solutions within a physiological range of temperatures and pHs. The polymers bear terminal reactive groups that allow for a mild, but effective chemical cross-linking. Given an appropriate temperature jump, the thermal gelation provides a hardening kinetics similar to that of alginate. With slower kinetics, the chemical cross-linking then develops an irreversible and elastic gel structure, and determines its transport properties. In the present article this process has been optimized for the production of monodisperse, high elastic, hydrogel microbeads, and liquid-core microcapsules. We also show the feasibility of the use of liquid-core microcapsules in cell encapsulation. In preliminary experiments, CHO cells have been successfully encapsulated preserving their viability during the process and after incubation. The advantages of this process are mainly in the use of synthetic polymers, which provide great flexibility in the molecular design. This, in principle, allows for a precise tailoring of mechanical and transport properties and of bioactivity of the hydrogels, and also for a precise control in material purification.

Evaluation of bioavailability, efficacy, and safety profile of doxorubicin-loaded solid lipid nanoparticles

NASA Astrophysics Data System (ADS)

Patro, Nagaraju M.; Devi, Kshama; Pai, Roopa S.; Suresh, Sarasija

2013-12-01

We investigated the bioavailability, efficacy, and toxicity of doxorubicin-loaded solid lipid nanoparticles (DOX-SLNs) prepared by a simple modified double-emulsification method. A 3-factor, 3-level Box-Behnken statistical design was adopted in the optimization of DOX-SLN formulation considering dependent factors particle size and entrapment efficiency. Optimized SLN formulation composed of lipid (2 %) consisting of soya lecithin and Precirol ATO 5 (1:3) with Pluronic F68 (0.3 %) resulted in 217.36 ± 3.31 nm particle size and 59.45 ± 1.75 % entrapment efficiency. DOX-SLN exhibited significant enhancement ( p < 0.05) in bioavailability as compared with free DOX in Sprague-Dawley (SD) rats. DOX-SLN exhibited higher peak plasma concentration (6.761 ± 0.08 vs. 2.412 ± 0.04 μg/ml), increased AUC (61.368 ± 3.54 vs. 5.812 ± 0.49 μg/ml h), decreased clearance (36 ± 0.01 vs. 619 ± 0.005 mL/h kg), and volume of distribution (733 ± 0.092 vs. 2,064 ± 0.061 mL/kg) when compared to free DOX. The collective results of cardiac and kidney enzyme assay, antioxidant enzyme levels, hematological parameters, effect on body weight and tumor volume, tumor necrosis factor-α level, histopathological examination, and survival analysis confirmed the improved efficacy and safety profile of DOX-SLN in 7,12-dimethyl benzanthracene-induced breast cancer in SD rats.

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents.

PubMed

Cavalli, R; Argenziano, M; Vigna, E; Giustetto, P; Torres, E; Aime, S; Terreno, E

2015-05-01

Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro- and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd(III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro. The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37°C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles. In summary, chitosan drug-loaded nanobubbles with Gd(III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anti-cancer treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

PubMed

Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

2015-01-01

Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

Optimizing Biomaterials for Tissue Engineering Human Bone Using Mesenchymal Stem Cells.

PubMed

Weinand, Christian; Neville, Craig M; Weinberg, Eli; Tabata, Yasuhiko; Vacanti, Joseph P

2016-03-01

Adequate biomaterials for tissue engineering bone and replacement of bone in clinical settings are still being developed. Previously, the combination of mesenchymal stem cells in hydrogels and calcium-based biomaterials in both in vitro and in vivo experiments has shown promising results. However, results may be optimized by careful selection of the material combination. β-Tricalcium phosphate scaffolds were three-dimensionally printed with five different hydrogels: collagen I, gelatin, fibrin glue, alginate, and Pluronic F-127. The scaffolds had eight channels, running throughout the entire scaffold, and macropores. Mesenchymal stem cells (2 × 10) were mixed with each hydrogel, and cell/hydrogel mixes were dispersed onto the corresponding β-tricalcium phosphate/hydrogel scaffold and cultured under dynamic-oscillating conditions for 6 weeks. Specimens were harvested at 1, 2, 4, and 6 weeks and evaluated histologically, radiologically, biomechanically and, at 6 weeks, for expression of bone-specific proteins by reverse-transcriptase polymerase chain reaction. Statistical correlation analysis was performed between radiologic densities in Hounsfield units and biomechanical stiffness. Collagen I samples had superior bone formation at 6 weeks as demonstrated by volume computed tomographic scanning, with densities of 300 HU, similar to native bone, and the highest compression values. Bone specificity of new tissue was confirmed histologically and by the expression of alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. The bone density correlated closely with histologic and biomechanical testing results. Bone formation is supported best by β-tricalcium phosphate/collagen I hydrogel and mesenchymal stem cells in collagen I hydrogel. Therapeutic, V.

pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation.

PubMed

Guha, Arijit; Biswas, Nikhil; Bhattacharjee, Kaustav; Sahoo, Nityananda; Kuotsu, Ketousetuo

2016-11-01

The objective of the present study was to develop novel PMV [poly (methacrylic acid-co-vinyl triethoxylsilane)]-coated mesoporous silica nanoparticles (MSN) with improved hypoglycemic effect for oral insulin (INS) delivery. MSN was synthesized under acidic condition using Pluronic® P 123 and Tetra ethoxy orthosilane. Surfactant was removed by calcination. Calcined MSN was coated with pH sensitive polymer PMV. Cytotoxicity of this coated MSN was evaluated by MTT assay using CHO-K1 cell line. Different MSN samples were characterized with BET surface area analyzer, FESEM, TEM, FT-IR, XRD, TG-DTA. In vivo study was performed using male rats. Pharmacokinetic study was conducted using HPLC. Highest surface area (304.3921 m 2 /g) was observed in case of calcined sample. Adsorption pore width of final coated sample was highest (64.7844 nm) compared with others. No noticeable cytotoxicity was observed for this coated support. The entrapment efficiency of insulin was found to be 39.39%. In vitro studies were done at different pH using Franz-diffusion cell. Results showed significant release at pH 7.4. Cumulative drug release over a period of 6 h was more than 48% at this systemic pH. Effect of this MSN-PMV-INS on blood glucose level was retained for 16 h. This novel formulation has shown 73.10% relative bioavailability of insulin. A novel-coated mesoporous silica support was successfully developed for delivery of insulin through oral route.

Incorporating poly(3-hexyl thiophene) into orthogonally aligned cylindrical nanopores of titania for optoelectronics

DOE PAGES

Nagpure, Suraj; Browning, James F.; Rankin, Stephen E.

2016-11-03

Here, the incorporation of hole conducting polymer poly(3-hexyl thiophene) (P3HT) into the 8-9 nm cylindrical nanopores of titania is investigated using films with a unique orthogonally oriented hexagonal close packed mesostructure. The films are synthesized using evaporation induced self-assembly (EISA) with Pluronic triblock copolymer F127 as the structure directing agent. The orthogonally oriented cylindrical nanopore structure was chosen over a cubic structure because confinement in uniform cylindrical channels is hypothesized to enhance hole conductivity of P3HT by inducing local polymer chain ordering. Orthogonal orientation of the cylindrical nanopores is achieved by modifying the substrate (FTO-coated glass slides) with crosslinked F127.more » After thermal treatment to remove organic templates from the films, P3HT is infiltrated into the nanopores by spin coating a 1 wt% P3HT solution in chlorobenzene onto the titania films followed by thermal annealing under vacuum at 200 °C. The results show that infiltration is essentially complete after 30 minutes of annealing, with little or no further infiltration thereafter. A final infiltration depth of ~14 nm is measured for P3HT into the nanopores of titania using neutron reflectometry measurements. Photoluminescence measurements demonstrate that charge transfer at the P3HT-TiO 2 interface improves as the P3HT is infiltrated into the pores, suggesting that an active organic-inorganic heterojuction is formed in the materials.« less

Incorporating poly(3-hexyl thiophene) into orthogonally aligned cylindrical nanopores of titania for optoelectronics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagpure, Suraj; Browning, James F.; Rankin, Stephen E.

Here, the incorporation of hole conducting polymer poly(3-hexyl thiophene) (P3HT) into the 8-9 nm cylindrical nanopores of titania is investigated using films with a unique orthogonally oriented hexagonal close packed mesostructure. The films are synthesized using evaporation induced self-assembly (EISA) with Pluronic triblock copolymer F127 as the structure directing agent. The orthogonally oriented cylindrical nanopore structure was chosen over a cubic structure because confinement in uniform cylindrical channels is hypothesized to enhance hole conductivity of P3HT by inducing local polymer chain ordering. Orthogonal orientation of the cylindrical nanopores is achieved by modifying the substrate (FTO-coated glass slides) with crosslinked F127.more » After thermal treatment to remove organic templates from the films, P3HT is infiltrated into the nanopores by spin coating a 1 wt% P3HT solution in chlorobenzene onto the titania films followed by thermal annealing under vacuum at 200 °C. The results show that infiltration is essentially complete after 30 minutes of annealing, with little or no further infiltration thereafter. A final infiltration depth of ~14 nm is measured for P3HT into the nanopores of titania using neutron reflectometry measurements. Photoluminescence measurements demonstrate that charge transfer at the P3HT-TiO 2 interface improves as the P3HT is infiltrated into the pores, suggesting that an active organic-inorganic heterojuction is formed in the materials.« less

Multifunctional polymeric micelles loaded with doxorubicin and poly(dithienyl-diketopyrrolopyrrole) for near-infrared light-controlled chemo-phototherapy of cancer cells.

PubMed

Liu, Hui; Wang, Kai; Yang, Cangjie; Huang, Shuo; Wang, Mingfeng

2017-09-01

Polymeric micelles loaded with multiple therapeutic modalities are important to overcome challenges such as drug resistance and improve the therapeutic efficacy. Here we report a new polymer micellar drug carrier that integrates chemotherapy and photothermal therapy in a single platform. Specifically, a narrow bandgap poly(dithienyl-diketopyrrolopyrrole) (PDPP) polymer was encapsulated together with a model anticancer drug doxorubicin (DOX) in the hydrophobic cores of polymeric micelles formed by Pluronic F127, an amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. The PDPP polymer served as an organic photothermal agent that absorbs near-infrared light (700-1000nm) and transforms into heat efficiently. The dual functional micelles co-loaded with PDPP and DOX in the hydrophobic compartment showed good colloidal stability after being stored at 4°C at least over two months, and remained visibly stable after 808-nm laser irradiation. The loaded DOX had negligible effect on the size and photothermal property of the micelles. The release of DOX from the micelles could be enhanced by the "breathing" effect of shrinking/swelling of the micelles induced by the temperature change, owing to the thermosensitive nature of the F127 polymers. Importantly, the ternary F127/PDPP/DOX micelles under 808-nm laser irradiation showed enhanced cytotoxicity against cancer cells such as HeLa cells, compared to F127 micelles containing single modality of either PDPP or DOX only. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-assembled pentablock copolymers for selective and sustained gene delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bingqi

2011-05-15

The poly(diethylaminoethyl methacrylate) (PDEAEM) - Pluronic F127 - PDEAEM pentablock copolymer (PB) gene delivery vector system has been found to possess an inherent selectivity in transfecting cancer cells over non-cancer cells in vitro, without attaching any targeting ligands. In order to understand the mechanism of this selective transfection, three possible intracellular barriers to transfection were investigated in both cancer and non-cancer cells. We concluded that escape from the endocytic pathway served as the primary intracellular barrier for PB-mediated transfection. Most likely, PB vectors were entrapped and rendered non-functional in acidic lysosomes of non-cancer cells, but survived in less acidic lysosomesmore » of cancer cells. The work highlights the importance of identifying intracellular barriers for different gene delivery systems and provides a new paradigm for designing targeting vectors based on intracellular differences between cell types, rather than through the use of targeting ligands. The PB vector was further developed to simultaneously deliver anticancer drugs and genes, which showed a synergistic effect demonstrated by significantly enhanced gene expression in vitro. Due to the thermosensitive gelation behavior, the PB vector packaging both drug and gene was also investigated for its in vitro sustained release properties by using polyethylene glycol diacrylate as a barrier gel to mimic the tumor matrix in vivo. Overall, this work resulted in the development of a gene delivery vector for sustained and selective gene delivery to tumor cells for cancer therapy.« less

Layering, melting, and recrystallization of a close-packed micellar crystal under steady and large-amplitude oscillatory shear flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Barrón, Carlos R., E-mail: carlos.r.lopez-barron@exxonmobil.com; Wagner, Norman J.; Porcar, Lionel

2015-05-15

The rheology and three-dimensional microstructure of a concentrated viscoelastic solution of the triblock copolymer poly(ethylene oxide){sub 106}-poly(propylene oxide){sub 68}-poly(ethylene oxide){sub 106} (Pluronic F127) in the protic ionic liquid ethylammonium nitrate are measured by small angle neutron scattering (SANS) under flow in three orthogonal planes. This solution's shear-thinning viscosity is due to the formation of two-dimensional hexagonal close-packed (HCP) sliding layer structure. Shear-melting of the crystalline structure is observed without disruption of the self-assembled micelles, resulting in a change in flow properties. Spatially resolved measurements in the 1–2 plane reveal that both shear-melting and sliding are not uniform across the Couettemore » gap. Melting and recrystallization of the HCP layers occur cyclically during a single large amplitude oscillatory shear (LAOS) cycle, in agreement with the “stick-slip” flow mechanism proposed by Hamley et al. [Phys. Rev. E 58, 7620–7628 (1998)]. Analysis of 3D “structural” Lissajous curves show that the cyclic melting and sliding are direct functions of the strain rate amplitude and show perfect correlation with the cyclic stress response during LAOS. Both viscosity and structural order obey the Delaware–Rutgers rule. Combining rheology with in situ spatiotemporally resolved SANS is demonstrated to elucidate the structural origins of the nonlinear rheology of complex fluids.« less

Effect of Surface Pore Structure of Nerve Guide Conduit on Peripheral Nerve Regeneration

PubMed Central

Oh, Se Heang; Kim, Jin Rae; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang

2013-01-01

Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration. PMID:22871377

Mesoporous Ga-TiO₂: Role of Oxygen Vacancies for the Photocatalytic Degradation Under Visible Light.

PubMed

Myilsamy, M; Mahalakshmi, M; Subha, N; Murugesan, V

2018-02-01

Gallium doped mesoporous TiO2 with different weight percentages were synthesized by sol-gel method using Pluronic P123 as the structure directing template. The physico-chemical properties of all the synthesized catalysts were determined by XRD, TEM, SEM-EDAX, N2 adsorption-desorption studies, XPS, UV-vis DRS, FT-IR and photoluminescence spectroscopy. 1.0 wt% Ga-TiO2 exhibited the highest photocatalytic efficiency among all the synthesized materials under visible light due to the high surface area, reduced band gap and suppressed electron-hole recombination. Ga3+ ions substitutions for Ti4+ ions in TiO2 lattice created oxygen vacancies in TiO2 lattice, which created a defect energy level below the conduction band of TiO2 and hence the band gap was reduced. The oxygen vacancy defects was playing significant role to improve the adsorption of oxygen molecules, hydroxide ions and cationic rhodamine B (RhB) on TiO2 surface in an aqueous medium. The lifetime of the charge carriers was also enhanced by trapping the photogenerated electrons in oxygen vacancies and transferring them to the adsorbed O2 to produce superoxide anion radicals (O-. 2 ). The photo-induced holes at valence band reduced the adsorbed OH- ions and produced a large number of .OH radicals, which subsequently degraded the RhB. Hence oxygen vacancies created by gallium doping on TiO2 enhanced the photocatalytic efficiency for the degradation of RhB under visible light.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

PubMed Central

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-01-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

Scalable preparation of porous micron-SnO2/C composites as high performance anode material for lithium ion battery

NASA Astrophysics Data System (ADS)

Wang, Ming-Shan; Lei, Ming; Wang, Zhi-Qiang; Zhao, Xing; Xu, Jun; Yang, Wei; Huang, Yun; Li, Xing

2016-03-01

Nano tin dioxide-carbon (SnO2/C) composites prepared by various carbon materials, such as carbon nanotubes, porous carbon, and graphene, have attracted extensive attention in wide fields. However, undesirable concerns of nanoparticles, including in higher surface area, low tap density, and self-agglomeration, greatly restricted their large-scale practical applications. In this study, novel porous micron-SnO2/C (p-SnO2/C) composites are scalable prepared by a simple hydrothermal approach using glucose as a carbon source and Pluronic F127 as a pore forming agent/soft template. The SnO2 nanoparticles were homogeneously dispersed in micron carbon spheres by assembly with F127/glucose. The continuous three-dimensional porous carbon networks have effectively provided strain relaxation for SnO2 volume expansion/shrinkage during lithium insertion/extraction. In addition, the carbon matrix could largely minimize the direct exposure of SnO2 to the electrolyte, thus ensure formation of stable solid electrolyte interface films. Moreover, the porous structure could also create efficient channels for the fast transport of lithium ions. As a consequence, the p-SnO2/C composites exhibit stable cycle performance, such as a high capacity retention of over 96% for 100 cycles at a current density of 200 mA g-1 and a long cycle life up to 800 times at a higher current density of 1000 mA g-1.

The performance of magnetic lens for focusing VCN-SANS

NASA Astrophysics Data System (ADS)

Nop Collaboration; Yamada, M.; Iwashita, Y.; Kanaya, T.; Ichikawa, M.; Tongu, H.; Kennedy, S. J.; Shimizu, H. M.; Mishima, K.; Yamada, N. L.; Hirota, K.; Carpenter, J. M.; Lal, J.; Andersen, K.; Geltenbort, P.; Guerard, B.; Manzin, G.; Hino, M.; Kitaguchi, M.; Bleuel, M.; NOP Collaboration

2011-04-01

We have developed a prototype rotating-permanent magnet sextupole lens (named rot-PMSx) for more efficient experiments with neutron beams in time of flight (ToF) mode. This lens can modulate the focusing strength over range 1.5×104T/m2⩽g‧⩽5.9×104T/m2. Synchronization between the modulation and the beam pulse produces a focused beam without significant chromatic aberration. We anticipate that this lens could be utilized in focusing small angle neutron scattering (SANS) instruments for novel approach to high resolution SANS.We carried out experiments testing the principle of this lens at the very cold neutron (VCN) beamline (PF2) at Institut Laue-Langevin (ILL), France. The focused beam image size at the detector was kept constant at the same beam size as the source (≈3mm) over a wavelength range of 30Å⩽λ⩽48Å in focal length of ≈1.14m. The flux gain was about 12 relative to a beam without focusing, and the depth of focus was quite large. These results show the good performance of this lens and the system. Thereupon we have demonstrated the performance of this test bed for high resolution focusing of VCN-SANS for a well-studied softmatter sample; a deuterium oxide solution of Pluronic F127, an (PEO)100(PPO)65(PEO)100 tri-block copolymer in deuterium oxide. The results of the focusing experiment and the focusing VCN-SANS are presented.

Optimization of perfluoro nano-scale emulsions: the importance of particle size for enhanced oxygen transfer in biomedical applications.

PubMed

Fraker, Christopher A; Mendez, Armando J; Inverardi, Luca; Ricordi, Camillo; Stabler, Cherie L

2012-10-01

Nano-scale emulsification has long been utilized by the food and cosmetics industry to maximize material delivery through increased surface area to volume ratios. More recently, these methods have been employed in the area of biomedical research to enhance and control the delivery of desired agents, as in perfluorocarbon emulsions for oxygen delivery. In this work, we evaluate critical factors for the optimization of PFC emulsions for use in cell-based applications. Cytotoxicity screening revealed minimal cytotoxicity of components, with the exception of one perfluorocarbon utilized for emulsion manufacture, perfluorooctylbromide (PFOB), and specific w% limitations of PEG-based surfactants utilized. We optimized the manufacture of stable nano-scale emulsions via evaluation of: component materials, emulsification time and pressure, and resulting particle size and temporal stability. The initial emulsion size was greatly dependent upon the emulsion surfactant tested, with pluronics providing the smallest size. Temporal stability of the nano-scale emulsions was directly related to the perfluorocarbon utilized, with perfluorotributylamine, FC-43, providing a highly stable emulsion, while perfluorodecalin, PFD, coalesced over time. The oxygen mass transfer, or diffusive permeability, of the resulting emulsions was also characterized. Our studies found particle size to be the critical factor affecting oxygen mass transfer, as increased micelle size resulted in reduced oxygen diffusion. Overall, this work demonstrates the importance of accurate characterization of emulsification parameters in order to generate stable, reproducible emulsions with the desired bio-delivery properties. Copyright © 2012 Elsevier B.V. All rights reserved.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

NASA Astrophysics Data System (ADS)

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-08-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles.

PubMed

Kennedy, Patrick J; Perreira, Ines; Ferreira, Daniel; Nestor, Marika; Oliveira, Carla; Granja, Pedro L; Sarmento, Bruno

2018-06-01

Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of ethanol on the gelation of aqueous solutions of Pluronic F127.

PubMed

Chaibundit, Chiraphon; Ricardo, Nágila M P S; Ricardo, Nádja M P S; Muryn, Christopher A; Madec, Marie-Beatrice; Yeates, Stephen G; Booth, Colin

2010-11-01

In dilute aqueous solution unimers of copolymer F127 (E(98)P(67)E(98)) associate to form micelles, and in more concentrated solution micelles pack to form high-modulus gels. Cosolvents are known to affect these processes, and ethanol/water mixtures have been of particular interest. Dynamic light scattering from dilute solutions was used to confirm micellization, but major attention was directed towards the gels. Visual observation of mobility (tube inversion) was used to detect gel formation, oscillatory rheometry to confirm gel formation and provide values of the elastic moduli over a wide temperature range, and small-angle X-ray scattering to determine gel structure. The solvents were limited to 10, 20 and 30 wt.% ethanol/water. Critical concentrations for gel formation were similar for 10 and 20 wt.% ethanol/water but were significantly increased for 30 wt.% ethanol/water, e.g. at T=45 degrees C from c approximately 15 wt.% to c approximately 28 wt.%. The elastic moduli reached maximum values at T approximately 50 degrees C: e.g. G' approximately 25 kPa for 25 wt.% F127 in 10 and 20 wt.% ethanol/water and a similar value for 30 wt.% F127 in 30 wt.% ethanol/water. Hard gels of 30 and 35 wt.% F127 in ethanol/water at 25 and 40 degrees C had the body-centered cubic (bcc) structure. Copyright 2010 Elsevier Inc. All rights reserved.

A facile synthesis of mesoporous Pdsbnd ZnO nanocomposites as efficient chemical sensor

NASA Astrophysics Data System (ADS)

Ismail, Adel A.; Harraz, Farid A.; Faisal, M.; El-Toni, Ahmed Mohamed; Al-Hajry, A.; Al-Assiri, M. S.

2016-07-01

Mesoporous ZnO was synthesized through the sol-gel method in the presence of triblock co-polymer Pluronic (F-127) template as the structure directing agent. Palladium nanoparticles were photochemically reduced and deposited onto mesoporous ZnO to obtain 1 wt.% Pd/ZnO nanocomposite. Structural and morphological analysis revealed high homogeneity and monodispersity of Pd nanoclusters with small particle sizes ∼ 2-5 nm onto mesoporous ZnO. The electrochemical detection of ethanol in aqueous solutions was conducted at the newly developed Pd/ZnO modified glassy carbon electrode (GCE) by the current-potential (IV) and cyclic voltammetry (CV) techniques and compared with bare GCE or pure ZnO. The presence of Pd dopant greatly enhances the sensitivity of ZnO, and the obtained mesoporous Pd/ZnO sensor has an excellent performance for precision detection of ethanol in aqueous solution with low concentration. The sensitivity was found to be 33.08 μAcm-2 mM-1 at lower concentration zone (0.05-0.8 mM) and 2.13 μAcm-2 mM-1 at higher concentration zone (0.8-12 mM), with a limit of detection (LOD) 19.2 μM. The kinetics study of ethanol oxidation revealed a characteristic feature for a mixed surface and diffusion-controlled process. These excellent sensing characteristics make the mesoporous Pd/ZnO nanocomposite a good candidate for the production of high-performance electrochemical sensors at low ethanol concentration in aqueous solution.

Floating lipid beads for the improvement of bioavailability of poorly soluble basic drugs: in-vitro optimization and in-vivo performance in humans.

PubMed

Abouelatta, Samar M; Aboelwafa, Ahmed A; Khalil, Rawia M; ElGazayerly, Omaima N

2015-01-01

The challenge in developing oral drug delivery systems of poorly soluble basic drugs is primarily due to their pH dependent solubility. Cinnarizine (CNZ), a model for a poorly soluble basic drug, has pH dependent solubility; where it dissolves readily at low pH in the stomach and exhibits a very low solubility at pH values greater than 4. It is also characterized by a short half life of 3-6h, which requires frequent daily administration resulting in poor patient compliance. In an attempt to solve these problems, extended release floating lipid beads were formulated. A 2(4) full factorial design was utilized for optimization of the effects of various independent variables; lipid:drug ratio, % Pluronic F-127, % Sterotex, and Gelucire 43/01:Gelucire 50/13 ratio, on the loading efficiency and release of CNZ from the lipid beads. In-vivo pharmacokinetic study of the optimized CNZ-lipid beads compared to Stugeron® (reference standard) was performed in healthy human volunteers. A promising approach for enhancing the bioavailability of the poorly soluble basic drug, CNZ, utilizing novel and simple floating lipid beads was successfully developed. Zero order release profile of CNZ was achieved for 12h. Mean AUC0-24 and AUC0-∞ of the optimized CNZ-loaded lipid beads were 4.23 and 6.04 times that of Stugeron® tablets respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

Rheological study of the effect of polyethylene oxide (PEO) homopolymer on the gelation of PEO-PPO-PEO triblock copolymer in aqueous solution

NASA Astrophysics Data System (ADS)

Li, Xiaolei; Hyun, Kyu

2018-05-01

The effects of polyethylene oxide (PEO) homopolymer on the gelation behavior of a PEO100-PPO65-PEO100 triblock copolymer (Pluronic F127) were explored in aqueous solution under non-isothermal and isothermal conditions. Under non-isothermal conditions (temperature sweep test), two transition points were observed on increasing temperature, that is, at lower and upper gelation temperatures (LTgel and UTgel, respectively). Between LTgel and UTgel, F127 aqueous solutions maintained a hard gel state. Both molecular weight (MW) and PEO concentration affected these two gelation temperatures. In particular, relative molecular weight (MWrel ≡ molecular weight of PEO homopolymer/PEO segment of F127) affected LTgel. LTgel decreased on increasing PEO concentration at MWrel values of <1, but increased on increasing PEO concentration at MWrel values of >1. On the other hand, UTgel decreased with increasing PEO concentration regardless of MWrel. Under isothermal conditions (fixed temperature between LTgel and UTgel), the effects of PEO homopolymer on the mechanical properties of F127 hard gel were systemically investigated using small and large amplitude oscillatory shear tests. In the linear viscoelastic regime, total intra-cycle stress and elastic intra-cycle stress were similar, and viscous response increased on increasing PEO concentration. However, at large strain amplitudes, hard gels showed intra-cycle stiffening but inter-cycle softening behavior. In addition, on increasing PEO concentrations, viscous nonlinearities underwent strain-rate thickening followed by strain-rate thinning.

Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation

PubMed Central

Xu, Wen-Hong; Han, Min; Dong, Qi; Fu, Zhi-Xuan; Diao, Yuan-Yuan; Liu, Hai; Xu, Jing; Jiang, Hong-Liang; Zhang, Su-Zhan; Zheng, Shu; Gao, Jian-Qing; Wei, Qi-Chun

2012-01-01

Background The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. Methods A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. Results Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. Conclusion Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer. PMID:22679376

Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

PubMed Central

Liu, Yuling; Xu, Yingqi; Wu, Minghui; Fan, Lijiao; He, Chengwei; Wan, Jian-Bo; Li, Peng; Chen, Meiwan; Li, Hui

2016-01-01

Mitoxantrone (MIT) is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES) amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT) micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50) value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines). In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. PMID:27471384

ICAM-1 Targeting of Doxorubicin-Loaded PLGA Nanoparticles to Lung Epithelial Cells

PubMed Central

Chuda, Chittasupho; Sheng-Xue, Xie; Abdulgader, Baoum; Tatyana, Yakovleva; Teruna, Siahaan J.; Cory, Berkland

2009-01-01

Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading, and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been indentified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to ICAM-1. In addition, cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic® surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1 mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-1 using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system. PMID:19429421

Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xiang; Zhang, Yuanwei; Takle, Kendra

2016-01-26

Near Infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) have recently been proposed in order to broaden the absorption range and to boost upconversion efficiency. However, implementing this strategy has been limited only to bare core UCNP structures that are faintly luminescent. Herein, we report on an approach to achieve significantly enhanced upconversion luminescence in dye-sensitized core-active shell UCNPs with a broadened absorption range via the doping of ytterbium ions in the UCNP shell in order to bridge the energy transfer from the dye to the UCNP core. As a result, we have been able to synergize the two most practical upconversionmore » booster effectors (dye-sensitizing and core/shell enhancement). The absolute quantum yield of our dye-sensitized core/active shell UCNPs at 800 nm was determined to be ~6% at 2 W/cm2, about 33 times larger than the highest value reported to date for existing 800 nm excitable UCNPs. Moreover, for the first time, by using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a wavelength that is compatible with deep tissue penetrable near the infrared wavelength at 800 nm. Finally, amphiphilic triblock copolymer, Pluronic F127 coatings permit the transfer of hydrophobic UCNPs into water, resulting in water-soluble nanoparticles with well-preserved optical property in aqueous solution. We believe that this research offers a new solution to enhance upconversion efficiency for photonic and biophotonic purposes and opens up new opportunities to use UCNPs as a NIR relay for optogenetic applications.« less

Multimaterial 3D Printing of Graphene-Based Electrodes for Electrochemical Energy Storage Using Thermoresponsive Inks.

PubMed

Rocha, Victoria G; García-Tuñón, Esther; Botas, Cristina; Markoulidis, Foivos; Feilden, Ezra; D'Elia, Eleonora; Ni, Na; Shaffer, Milo; Saiz, Eduardo

2017-10-25

The current lifestyles, increasing population, and limited resources result in energy research being at the forefront of worldwide grand challenges, increasing the demand for sustainable and more efficient energy devices. In this context, additive manufacturing brings the possibility of making electrodes and electrical energy storage devices in any desired three-dimensional (3D) shape and dimensions, while preserving the multifunctional properties of the active materials in terms of surface area and conductivity. This paves the way to optimized and more efficient designs for energy devices. Here, we describe how three-dimensional (3D) printing will allow the fabrication of bespoke devices, with complex geometries, tailored to fit specific requirements and applications, by designing water-based thermoresponsive inks to 3D-print different materials in one step, for example, printing the active material precursor (reduced chemically modified graphene (rCMG)) and the current collector (copper) for supercapacitors or anodes for lithium-ion batteries. The formulation of thermoresponsive inks using Pluronic F127 provides an aqueous-based, robust, flexible, and easily upscalable approach. The devices are designed to provide low resistance interface, enhanced electrical properties, mechanical performance, packing of rCMG, and low active material density while facilitating the postprocessing of the multicomponent 3D-printed structures. The electrode materials are selected to match postprocessing conditions. The reduction of the active material (rCMG) and sintering of the current collector (Cu) take place simultaneously. The electrochemical performance of the rCMG-based self-standing binder-free electrode and the two materials coupled rCMG/Cu printed electrode prove the potential of multimaterial printing in energy applications.

Synthesis, characterization, and catalytic application of ordered mesoporous carbon–niobium oxide composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Juan-Li; Gao, Shuang; Liu, Chun-Ling

2014-11-15

Graphical abstract: The ordered mesoporous carbon–niobium oxide composites have been synthesized by a multi-component co-assembly method associated with a carbonization process. - Highlights: • Ordered mesoporous carbon–niobium oxide composites were synthesized. • The content of Nb{sub 2}O{sub 5} in the composites could be tuned from 38 to 75%. • Niobium species were highly dispersed in amorphous carbon framework walls. • The composites exhibited good catalytic performance in the dehydration of fructose. - Abstract: Ordered mesoporous carbon–niobium oxide composites have been synthesized by a multi-component co-assembly method associated with a carbonization process using phenolic resol as carbon source, niobium chloride asmore » precursor and amphiphilic triblock copolymer Pluronic F127 as template. The resulting materials were characterized using a combination of techniques including differential scanning calorimetry–thermogravimetric analysis, N{sub 2} physical adsorption, X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. The results show that with increasing the content of Nb{sub 2}O{sub 5} from 38 to 75% the specific surface area decreases from 306.4 to 124.5 m{sup 2} g{sup −1}, while the ordered mesoporous structure is remained. Niobium species is well dispersed in the amorphous carbon framework. The mesoporous carbon–niobium oxide composites exhibit high catalytic activity in the dehydration of fructose to 5-hydroxymethylfurfural. A 100% conversion of fructose and a 76.5% selectivity of 5-hydroxymethylfurfural were obtained over the carbon–niobium oxide composite containing 75% Nb{sub 2}O{sub 5} under the investigated reaction conditions.« less