Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

PubMed

Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

2016-09-10

NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

PubMed

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Controlled-release of tea polyphenol from gelatin films incorporated with different ratios of free/nanoencapsulated tea polyphenols into fatty food simulants

USDA-ARS?s Scientific Manuscript database

Gelatin films having controlled-release properties were developed by incorporation of different free/encapsulated tea polyphenol (TP) ratios through modifying the encapsulation efficiency (EE) of TP-loaded chitosan nanoparticles. Different EEs were obtained by adjusting the chitosan hydrochloride (C...

Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study.

PubMed

Pimenta, A F R; Vieira, A P; Colaço, R; Saramago, B; Gil, M H; Coimbra, P; Alves, P; Bozukova, D; Correia, T R; Correia, I J; Guiomar, A J; Serro, A P

2017-08-01

Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release.

PubMed

Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

2015-01-01

Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery.

alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals.

PubMed

Donoso, M Veronica; Carvajal, Andrés; Paredes, Alfonso; Tomic, Alexander; Koenig, Cecilia S; Huidobro-Toro, J Pablo

2002-09-01

Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms.

Drug delivery from hydrophobic-modified mesoporous silicas: Control via modification level and site-selective modification

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

Tang Qunli, E-mail: tangqunli@hnu.c; State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001; Chen Yuxi

2010-01-15

Dimethylsilyl (DMS) modified mesoporous silicas were successfully prepared via co-condensation and post-grafting modification methods. The post-grafting modification was carried out by the reaction of the as-synthesized MCM-41 material (before CTAB removal) with diethoxydimethylsinale (DEDMS). N{sub 2} adsorption-desorption and {sup 29}Si MAS NMR characterization demonstrated that different amount of DMS groups were successfully incorporated into the co-condensation modified samples, and the functional DMS groups were placed selectively on the pore openings and external pore surfaces in the post-grafting modified samples. Subsequently, the controlled drug delivery properties from the resulting DMS-modified mesoporous silicas were investigated in detail. The drug adsorption experiments showedmore » that the adsorption capacities were mainly depended on the content of silanol group (CSG) in the corresponding carriers. The in vitro tests exhibited that the incorporation of DMS groups greatly retarded the ibuprofen release rate. Moreover, the ibuprofen release profiles could be well modulated by varying DMS modification levels and site-selective distribution of functional groups in mesoporous carriers. - The distribution of DMS groups on the pore surfaces of the mesostructures strongly affects the drug release rate. The P-M41-1 and the P-M41-2 possess the close DMS modification levels as the C-M41-10, but the ibuprofen release rates from the P-M41-1 and P-M41-2 are much slower than that from the C-M41-10.« less

Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

PubMed Central

Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

2011-01-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix. PMID:21731354

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

PubMed

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Modifying the release of leuprolide from spray dried OED microparticles.

PubMed

Alcock, R; Blair, J A; O'Mahony, D J; Raoof, A; Quirk, A V

2002-08-21

A range of oligosaccharide ester derivatives (OEDs) have been designed as drug delivery matrices for controlled release. The synthetic hormone analogue, leuprolide, was encapsulated within these matrices using hydrophobic ion pairing and solvent spray drying. The particles produced modified the release of leuprolide in vitro (dissolution in phosphate buffered saline) and in vivo (subcutaneous and pulmonary delivery in the rat). Release rate was dependent on drug loading and could be manipulated by choice of OED and by combining different OEDs in different ratios. Leuprolide encapsulated in the OEDs retained biological activity as evidenced by elevation in plasma luteinising hormone levels following subcutaneous injection of leuprolide recovered from OED particles in vitro prior to in vivo administration.

Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

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

Szegedi, A., E-mail: szegedi@chemres.h; Popova, M.; Goshev, I.

2011-05-15

MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choicemore » of mesoporous material with the appropriate structural characteristics and surface functionality. -- Graphical Abstract: Ibuprofen delivery from the parent and amino-modified spherical MCM-41 materials with 100 nm (small) and 500 nm (large) particle sizes. Display Omitted Highlights: {yields} Spherical type MCM-41 and SBA-15 with different particle sizes were modified by APTES. {yields} Adsorption and release rate of ibuprofen were compared. {yields} High degree of ibuprofen loading, slow release rate for MCM-41, the opposite for SBA-15. {yields} MCM-41 with 100 nm particles was more stable and showed slower release rate« less

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.

Fabrication of a bioadhesive transdermal device from chitosan and hyaluronic acid for the controlled release of lidocaine.

PubMed

Anirudhan, T S; Nair, Syam S; Nair, Anoop S

2016-11-05

A novel efficient transdermal (TD) lidocaine (LD) delivery device based on chitosan (CS) and hyaluronic acid (HA) was successfully developed in the present investigation. CS was grafted with glycidyl methacrylate (GMA) and butyl methacrylate (BMA) to fabricate a versatile material with improved adhesion and mechanical properties. HA was hydrophobically modified by covalently conjugating 3-(dimethylamino)-1-propylamine (DMPA) to encapsulate poorly water soluble LD and was uniformly dispersed in modified CS matrix. The prepared materials were characterized through FTIR, NMR, XRD, SEM, TEM and tensile assay. The dispersion of amine functionalized HA (AHA) on modified CS matrix offered strong matrix - filler interaction, which improved the mechanical properties and drug retention behavior of the device. In vitro skin permeation study of LD was performed with modified Franz diffusion cell using rat skin and exhibited controlled release. The influence of storage time on release profile was investigated and demonstrated that after the initial burst, LD release profile of the device after 30 and 60days storage was identical to that of a device which was not stored. In vivo skin adhesion test and skin irritation assay in human subjects, water vapor permeability and environmental fitness test was performed to judge its application in biomedical field. All results displayed that the fabricated device is a potential candidate for TD LD administration to the systemic circulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

PubMed

Garrido-Herrera, F J; Gonzalez-Pradas, E; Fernandez-Pérez, M

2006-12-27

Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

Natural gum-type biopolymers as potential modified nonpolar drug release systems.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Moreno, Roger A; Prieto, Vanessa; Recalde, Juanita

2018-06-01

In this work, the relationship between surface properties and drug release mechanism from binary composition tablets formed by quetiapine fumarate and biopolymer materials was studied. The biopolymers correspond to xanthan and tragacanth gums, which are projected as modified drug release systems. The surface studies were carried out by the sessile drop method, while the surface free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical models. On the other hand, the drug release studies were performed by in vitro dissolution tests, where the data were analyzed through kinetic models of zero order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that depending on the type and the proportion of biopolymer, surface properties, and the drug release processes are significantly affected, wherein tragacanth gum present a usual erosion mechanism, while xanthan gum describes a swelling mechanism that controls the release of the drug. Copyright © 2018 Elsevier Ltd. All rights reserved.

Release of betaine and dexpanthenol from vitamin E modified silicone-hydrogel contact lenses.

PubMed

Hsu, Kuan-Hui; de la Jara, Percy Lazon; Ariyavidana, Amali; Watling, Jason; Holden, Brien; Garrett, Qian; Chauhan, Anuj

2015-03-01

To develop a contact lens system that will control the release of an osmoprotectant and a moisturizing agent with the aim to reduce symptoms of ocular dryness. Profiles of the release of osmoprotectant betaine and moisturizing agent dexpanthenol from senofilcon A and narafilcon B contact lenses were determined in vitro under sink conditions. Both types of lenses were also infused with vitamin E to increase the duration of drug release due to the formation of the vitamin E diffusion barriers in the lenses. The release profiles from vitamin E-infused lenses were compared with those from the control lenses. Both dexpanthenol and betaine are released from commercial silicone hydrogel lenses for only about 10 min. Vitamin E loadings into contact lenses at about 20-23% can increase the release times to about 10 h, which is about 60 times larger compared to the control unmodified lenses. Vitamin E-loaded silicone hydrogel contact lenses released betaine and dexpanthenol in a controlled fashion.

In vitro and in vivo evaluation of novel ciprofloxacin-releasing silicone hydrogel contact lenses.

PubMed

Hui, Alex; Willcox, Mark; Jones, Lyndon

2014-07-15

The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P < 0.05). In vivo, there was no statistically significant difference between the number of colony-forming units (CFU) recovered from corneas treated with eye drops and those treated with one of two modified contact lenses (P > 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Semiochemical lures reduce emigration and enhance pest control services in open-field predator augmentation

USDA-ARS?s Scientific Manuscript database

Augmentation biocontrol is a commercially viable pest management tactic in enclosed glasshouse environments, but is far less effective in open-field agriculture where newly released enemies rapidly disperse from release sites. We tested the potential for behavior-modifying semiochemicals to increase...

Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

NASA Astrophysics Data System (ADS)

Gao, Lin; Sun, Jihong; Li, Yuzhen

2011-08-01

The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

Synthesis of bio-based nanocomposites for controlled release of antimicrobial agents in food packaging

NASA Astrophysics Data System (ADS)

DeGruson, Min Liu

The utilization of bio-based polymers as packaging materials has attracted great attention in both scientific and industrial areas due to the non-renewable and nondegradable nature of synthetic plastic packaging. Polyhydroxyalkanoate (PHA) is a biobased polymer with excellent film-forming and coating properties, but exhibits brittleness, insufficient gas barrier properties, and poor thermal stability. The overall goal of the project was to develop the polyhydroxyalkanoate-based bio-nanocomposite films modified by antimicrobial agents with improved mechanical and gas barrier properties, along with a controlled release rate of antimicrobial agents for the inhibition of foodborne pathogens and fungi in food. The ability for antimicrobial agents to intercalate into layered double hydroxides depended on the nature of the antimicrobial agents, such as size, spatial structure, and polarity, etc. Benzoate and gallate anions were successfully intercalated into LDH in the present study and different amounts of benzoate anion were loaded into LDH under different reaction conditions. Incorporation of nanoparticles showed no significant effect on mechanical properties of polyhydroxybutyrate (PHB) films, however, significantly increased the tensile strength and elongation at break of polyhydroxybutyrate-co-valerate (PHBV) films. The effects of type and concentration of LDH nanoparticles (unmodified LDH and LDH modified by sodium benzoate and sodium gallate) on structure and properties of PHBV films were then studied. The arrangement of LDH in the bio-nanocomposite matrices ranged from exfoliated to phase-separated depending on the type and concentration of LDH nanoparticles. Intercalated or partially exfoliated structures were obtained using modified LDH, however, only phase-separated structures were formed using unmodified LDH. The mechanical (tensile strength and elongation at break) and thermo-mechanical (storage modulus) properties were significantly improved with low concentrations of nanoparticles incorporated into the polymer. The incorporation of LDH modified by sodium benzoate further improved the mechanical properties in comparison with unmodified LDH, which may be due to the increased compatibility between PHBV and nanoparticles and the larger basal distance between nanolayers after modification. The concentration of benzoate anions in LDH nanoparticles was another factor which affected the properties of PHBV composite films. The PHBV film with 2% modified LDH with 20.9 % w/w of benzoate anions in LDH had the best mechanical and thermomechanical properties. Apparent glass transition temperature increased with the addition of modified LDH but did not change with the addition of unmodified LDH. Moreover, the effect of nanoparticles on thermal properties as well as crystallization of PHBV composites was dependent on the type of nanoparticles. A comparison of mechanical properties and release kinetics of antimicrobial agents directly dispersed in PHBV and modified in LDH and then dispersed in PHBV was made. The results indicated that mechanical properties increased and release rate decreased in the latter case. The release of benzoate and gallate into DI water from PHBV composite films with LDH modified by benzoate and gallate followed pseudo-Fickian behavior fitted with a power law model. The release of benzoate from PHBV composite films with LDH modified by benzoate was also fitted with a Weibull model indicating Fickian behavior in fractal substrate morphologically similar to the percolation cluster. The concentration of modified LDH and the loading of benzoate in modified LDH showed a significant effect on the release kinetics of benzoate. The diffusivities of benzoate at 21 °C ranged from 3.41 to14.97 x 10-16 m 2/s. The slowest release rate was achieved by the PHBV film containing 5 % w/w of modified LDH with medium loading of benzoate (21 % w/w of benzoate) in nanoparticles. The release of gallate from PHBV was much faster than that of benzoate. The effective diffusivity of benzoate increased with increase of temperature and the activation energy Ea for benzoate diffusion was calculated as 66.4 kJ/mol. It will be thus possible to design biodegradable polymeric nanocomposites with a tunable release of active molecules for various applications. (Abstract shortened by UMI.).

Biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres for controlled drug release.

PubMed

Du, Pengcheng; Zeng, Jin; Mu, Bin; Liu, Peng

2013-05-06

Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.

Multimodal nanoporous silica nanoparticles functionalized with aminopropyl groups for improving loading and controlled release of doxorubicin hydrochloride.

PubMed

Wang, Xin; Li, Chang; Fan, Na; Li, Jing; He, Zhonggui; Sun, Jin

2017-09-01

The purpose of this study was to develop amino modified multimodal nanoporous silica nanoparticles (M-NSNs-NH 2 ) loaded with doxorubicin hydrochloride (DOX), intended to enhance the drug loading capacity and to achieve controlled release effect. M-NSNs were functionalized with aminopropyl groups through post-synthesis. The contribution of large pore sizes and surface chemical groups on DOX loading and release were systemically studied using transmission electron microscope (TEM), nitrogen adsorption/desorption measurement, Fourier transform infrared spectroscopy (FTIR), zeta potential analysis, X-ray photoelectron spectroscopy (XPS) and ultraviolet spectrophotometer (UV). The results demonstrated that the NSNs were functionalized with aminopropyl successfully and the DOX molecules were adsorbed inside the nanopores by the hydrogen bonding. The release performance indicated that DOX loaded M-NSNs significantly controlled DOX release, furthermore DOX loaded M-NSNs-NH 2 performed slower controlled release, which was mainly attributed to its stronger hydrogen bonding forces. As expected, we developed a novel carrier with high drug loading capacity and controlled release for DOX. Copyright © 2017 Elsevier B.V. All rights reserved.

PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion.

PubMed

Li, Yongcheng; Lu, Ming; Wu, Chuanbin

2017-11-10

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50-100% in 24 h with the addition of 20-40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.

Modified hydraulic braking system limits angular deceleration to safe values

NASA Technical Reports Server (NTRS)

Briggs, R. S.; Council, M.; Green, P. M.

1966-01-01

Conventional spring actuated, hydraulically released, fail-safe disk braking system is modified to control the angular deceleration of a massive antenna. The hydraulic system provides an immediate preset pressure to the spring-loaded brake shoes and holds it at this value to decelerate the antenna at the desired rate.

The controlled release of bioactive compounds from lignin and lignin-based biopolymer matrices.

PubMed

Chowdhury, Mohammad A

2014-04-01

This article presents the perspectives on the lignin-based controlled release (CR) of bioactive materials which are based on the researches that took place over the last three decades. It encompasses three broad spectra of observations: CR formulations with mixed-matrix of lignin; CR formulations with modified lignin; and the lignin-based CR formulation modelling. The article covers a range of bioactive materials aimed for agricultural utilisations viz. herbicides, pesticides, insecticides and fertilisers for their controlled release studies, which were formulated either with lignin or lignin-based biopolymers. The inherent complexities, structural heterogeneities, and the presence of myriad range of functionalities in the lignin structure make it difficult to understand and explaining the underlying CR behaviour and process. In conjunction to this issue, the fundamental aspects of the synthetic and biocompatible polymer-based drug controlled release process are presented, and correlated with the lignin-based CR research. The articulation of this correlation and the overview presented in this article may be complemented of the future lignin-based CR research gaining better insights, reflections, and understanding. A recommended approach on the lignin depolymerisation is suggested to fragmenting the lignin, which may be tailored further using the re-polymerisation or other synthetic approaches. Thus it may allow more control with flexibilities and improved properties of the modified lignin materials, and help achieve the desired CR outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

PubMed Central

Pakulska, Malgosia M.; Elliott Donaghue, Irja; Obermeyer, Jaclyn M.; Tuladhar, Anup; McLaughlin, Christopher K.; Shendruk, Tyler N.; Shoichet, Molly S.

2016-01-01

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID:27386554

Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

PubMed

Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

2012-01-01

We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

The effects of heat treatment on selected properties of a conventional and a resin-modified glass ionomer cement.

PubMed

Rafeek, Reisha N

2008-05-01

This study investigated the effects of application of heat alone and heat & pressure on the compressive strength and modulus, the stress relaxation characteristics and the fluoride release of a conventional and a resin-modified glass ionomer cement. Cylindrical specimens were made from both materials and divided into 3 groups. One group was heat treated in an oven at 120 degrees C for 20 min, another group was subjected to heat & pressure at 120 degrees C for 20 min at 6-bar pressure. The third group acted as a control. The compressive strength and modulus, stress relaxation and fluoride release were tested over 56 days. The results of this investigation indicate that heat treatment had no significant effect on the conventional GIC used but significantly affected the resin modified GIC by increasing both the compressive strength and modulus and reducing the stress relaxation characteristics and the fluoride release. The use of GIC to produce inlay or onlay restorations that adhere to tooth tissue and release fluoride would be highly desirable. The results of this study indicate that it is possible to improve the strength of RMGIC with heat to a limited extent, but fluoride release may decrease.

Controlled drug release on amine functionalized spherical MCM-41

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

Szegedi, Agnes, E-mail: szegedi@chemres.hu; Popova, Margarita; Goshev, Ivan

2012-10-15

MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin methodmore » and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.« less

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents.

PubMed

O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P

2017-01-15

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modified Therapeutic Community Treatment for Offenders with Co-Occurring Disorders: Mental Health Outcomes

ERIC Educational Resources Information Center

Sullivan, Christopher J.; Sacks, Stanley; McKendrick, Karen; Banks, Steven; Sacks, Joann Y.; Stommel, Joseph

2007-01-01

This paper examines outcomes 12 months post-prison release for offenders with co-occurring disorders (n = 185) randomly assigned to either a mental health control treatment (C) or a modified therapeutic community (E). Significant between-group differences were not found for mental health measures, although improvements were observed for each…

Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs.

PubMed

Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Hansen, Richard

2016-04-01

Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

PubMed

Rehman, Fozia; Rahim, Abdur; Airoldi, Claudio; Volpe, Pedro L O

2016-02-01

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

PubMed Central

Liu, Hongzhuo; Feng, Liang; Tolia, Gaurav; Liddell, Mark R.; Hao, Jinsong; Li, S. Kevin

2013-01-01

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions. PMID:23631539

Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

PubMed

Arcan, Iskender; Yemenicioğlu, Ahmet

2014-08-13

To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food.

Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

PubMed

Skripnik, K K S; Riekes, M K; Pezzini, B R; Cardoso, S G; Stulzer, H K

2017-07-01

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

PubMed

Pérez Quiñones, Javier; Brüggemann, Oliver; Kjems, Jørgen; Shahavi, Mohammad Hassan; Peniche Covas, Carlos

2018-02-21

Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

PubMed

Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

2013-07-01

There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrating sol-gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

NASA Astrophysics Data System (ADS)

Mangindaan, Dave; Chen, Chao-Ting; Wang, Meng-Jiy

2012-12-01

A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)-chitosan sol-gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS-chitosan sol-gel. The surface modification was achieved by O2 plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O2 plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

Antagonism of specific corticotropin-releasing factor receptor subtypes selectively modifies weight loss in restrained rats.

PubMed

Chotiwat, Christina; Harris, Ruth B S

2008-12-01

Rats exposed to 3 h of restraint stress on each of 3 days (RRS) lose weight on the days of RRS and gain weight at the same rate as controls after stress ends, but do not return to the weight of controls. RRS rats also show an exaggerated endocrine response to subsequent novel stressors. Studies described here tested the effects of corticotropin-releasing factor receptor (CRFR) antagonism on RRS-induced weight loss, hypophagia, and corticosterone release during mild stress in the postrestraint period. Weight loss was not prevented by either peripheral or third-ventricle administration of a CRFR1 antagonist, antalarmin, before each restraint. Antalarmin did, however, allow recovery of body weight in the poststress period. Third-ventricle administration of a CRFR2 antagonist, antisauvagine 30, had no effect in RRS rats but caused sustained weight loss in control animals. Surprisingly, third-ventricle administration of the nonselective CRFR antagonist, astressin, caused hypophagia and reversible weight loss in control rats. It had no effect in RRS rats. None of the antagonists modified the corticosterone response to RRS or to mild stress in the post-RRS period, but antalarmin suppressed corticosterone during the period of restraint in Control rats. These results suggest that CRFR1 activation is required for the initiation of events that lead to a prolonged down-regulation of body weight in RRS rats. The sustained reduction in body weight is independent of the severity of hypophagia on the days of restraint and of RRS-induced corticosterone release.

Zinc-decorated silica-coated magnetic nanoparticles for protein binding and controlled release.

PubMed

Bele, Marjan; Hribar, Gorazd; Campelj, Stanislav; Makovec, Darko; Gaberc-Porekar, Vladka; Zorko, Milena; Gaberscek, Miran; Jamnik, Janko; Venturini, Peter

2008-05-01

The aim of this study was to be able to reversibly bind histidine-rich proteins to the surface of maghemite magnetic nanoparticles via coordinative bonding using Zn ions as the anchoring points. We showed that in order to adsorb Zn ions on the maghemite, the surface of the latter needs to be modified. As silica is known to strongly adsorb zinc ions, we chose to modify the maghemite nanoparticles with a nanometre-thick silica layer. This layer appeared to be thin enough for the maghemite nanoparticles to preserve their superparamagnetic nature. As a model the histidine-rich protein bovine serum albumin (BSA) was used. The release of the BSA bound to Zn-decorated silica-coated maghemite nanoparticles was analysed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We demonstrated that the bonding of the BSA to such modified magnetic nanoparticles is highly reversible and can be controlled by an appropriate change of the external conditions, such as a pH decrease or the presence/supply of other chelating compounds.

Quantitative Microbial Risk Assessment Tutorial - SDMProjectBuilder: Import Local Data Files to Identify and Modify Contamination Sources and Input ParametersUpdated 2017

EPA Science Inventory

Twelve example local data support files are automatically downloaded when the SDMProjectBuilder is installed on a computer. They allow the user to modify values to parameters that impact the release, migration, fate, and transport of microbes within a watershed, and control delin...

Quantitative Microbial Risk Assessment Tutorial – SDMProjectBuilder: Import Local Data Files to Identify and Modify Contamination Sources and Input Parameters

EPA Science Inventory

Twelve example local data support files are automatically downloaded when the SDMProjectBuilder is installed on a computer. They allow the user to modify values to parameters that impact the release, migration, fate, and transport of microbes within a watershed, and control delin...

Ordered cubic nanoporous silica support MCM-48 for delivery of poorly soluble drug indomethacin

NASA Astrophysics Data System (ADS)

Zeleňák, Vladimír; Halamová, Dáša; Almáši, Miroslav; Žid, Lukáš; Zeleňáková, Adriána; Kapusta, Ondrej

2018-06-01

Ordered MCM-48 nanoporous silica (SBET = 923(3) m2·g-1, VP = 0.63(2) cm3·g-1) with cubic Ia3d symmetry was used as a support for drug delivery of anti-inflammatory poorly soluble drug indomethacin. The delivery from parent, unmodified MCM-48, and 3-aminopropyl modified silica carrier was studied into the simulated body fluids with the pH = 2 and pH = 7.4. The studied samples were characterized by thermal analysis (TG/DTG-DTA), N2 adsorption/desorption, infrared spectroscopy (FT-IR), powder XRD, SEM, HRTEM methods, measurements of zeta potential (ζ) and dynamic light scattering (DLS). The determined content of indomethacin in pure MCM-48 was 21 wt.% and in the amine-modified silica MCM-48A-I the content was 45 wt.%. The release profile of the drug, in the time period up to 72 h, was monitored by TLC chromatographic method. It as shown, that by the modification of the surface, the drug release can be controlled. The slower release of indomethacin was observed from amino modified sample MCM-48A-I in the both types of studied simulated body fluids (slightly alkaline intravenous solution with pH = 7.4 and acidic gastric fluid with pH = 2), which was supported and explained by zeta potential and DLS measurements. The amount of the released indomethacin into the fluids with various pH was different. The maximum released amount of the drug was 97% for sample containing unmodified silica, MCM-48-I at pH = 7.4 and lowest released amount, 57%, for amine modified sample MCM-48A-I at pH = 2. To compare the indomethacin release profile four kinetic models were tested. Results showed, that that the drug release based on diffusion Higuchi model, mainly governs the release.

Preparation of dual-stimuli-responsive liposomes using methacrylate-based copolymers with pH and temperature sensitivities for precisely controlled release.

PubMed

Sugimoto, Takumi; Yamazaki, Naoko; Hayashi, Takaaki; Yuba, Eiji; Harada, Atsushi; Kotaka, Aki; Shinde, Chiharu; Kumei, Takayuki; Sumida, Yasushi; Fukushima, Mitsuhiro; Munekata, Yuki; Maruyama, Keiichi; Kono, Kenji

2017-07-01

Dual-signal-sensitive copolymers were synthesized by copolymerization of methoxy diethylene glycol methacrylate, methacrylic acid, and lauroxy tetraethylene glycol methacrylate, which respectively provide temperature sensitivity, pH sensitivity, and anchoring to liposome surfaces. These novel copolymers, with water solubility that differs depending on temperature and pH, are soluble in water under neutral pH and low-temperature conditions, but they become water-insoluble and form aggregates under acidic pH and high-temperature conditions. Liposomes modified with these copolymers exhibited enhanced content release at weakly acidic pH with increasing temperature, although no temperature-dependent content release was observed in neutral conditions. Interaction between the copolymers and the lipid monolayer at the air-water interface revealed that the copolymer chains penetrate more deeply into the monolayer with increasing temperature at acidic pH than at neutral pH, where the penetration of copolymer chains was moderate and temperature-independent at neutral pH. Interaction of the copolymer-modified liposomes with HeLa cells demonstrated that the copolymer-modified liposomes were adsorbed quickly and efficiently onto the cell surface and that they were internalized more gradually than the unmodified liposomes through endocytosis. Furthermore, the copolymer-modified liposomes enhanced the content release in endosomes with increasing temperature, but no such temperature-dependent enhancement of content release was observed for unmodified liposomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and drug release properties of chitosan/organomodified palygorskite microspheres.

PubMed

Wu, Jie; Ding, Shijie; Chen, Jing; Zhou, Suqin; Ding, Hongyan

2014-07-01

The novel composite microspheres, based on the hybridization of chitosan (CS) and organomodified palygorskite (OPAL), were prepared by emulsion cross-linking technique and applied as a drug carrier. Palygorskite, a kind of natural one-dimensional clay, was modified with hexadecyl betaine (BS-16) to improve the compatibility and affinity with chitosan matrix, and worked as a perfect micron-filler to enhance drug encapsulation and retard drug migration. The structure of the microspheres was characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The swelling behavior of the microspheres and the effect of the amount of OPAL and BS-16 on the properties of the drug loading and releasing have been investigated. Compared to the pure chitosan microspheres (CM), the composite one with 20wt% OPAL modified by 20mmol/100g BS-16 possessed the higher encapsulation efficiency and the slower and continuous cumulative release for diclofenac sodium (DS) in phosphate buffer solution (pH 6.8). The study of drug release kinetics in vitro found that the drug release mechanism of the microspheres changed from the simple diffusion-control to diffusion and dissolution-control as the OPAL content in matrix increased from 0 to 20wt%. Copyright © 2014 Elsevier B.V. All rights reserved.

Bio-based Interpenetrating Network Polymer Composites from Locust Sawdust as Coating Material for Environmentally Friendly Controlled-Release Urea Fertilizers.

PubMed

Zhang, Shugang; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Zhao, Chenhao

2016-07-20

A novel polymer-coated nitrogen (N) fertilizer was developed using bio-based polyurethane (PU) derived from liquefied locust sawdust as the coating material. The bio-based PU was successfully coated on the surface of the urea fertilizer prills to form polymer-coated urea (PCU) fertilizer for controlled N release. Epoxy resin (EP) was also used to further modify the bio-based PU to synthesize the interpenetrating network (IPN), enhancing the slow-release properties of the PCU. The N release characteristics of the EP-modified PCU (EMPCU) in water were determine at 25 °C and compared to that of PCU and EP-coated urea (ECU). The results showed that the EP modification reduced the N release rate and increased the longevity of the fertilizer coated with bio-based PU. A corn growth study was conducted to further evaluate the filed application of the EMPCU. In comparison to commercial PCU and conventional urea fertilizer, EMPCU was more effective and increased the yield and total dry matter accumulation of the corn. Findings from this work indicated that bio-based PU derived from sawdust can be used as coating materials for PCU, particularly after EP modification. The resulting EMPCU was more environmentally friendly and cost-effective than conventional urea fertilizers coated by EP.

Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

PubMed Central

Vijayakumar, Vediappan; Subramanian, Kaliappagounder

2013-01-01

Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

Biopharmaceutical evaluation of time-controlled press-coated tablets containing polymers to adjust drug release.

PubMed

Halsas, M; Ervasti, P; Veski, P; Jürjenson, H; Marvola, M

1998-01-01

This paper deals with press-coated modified release tablets in which the drug dose is situated in the core or is divided between the core and the coat. The coat contains polymer (sodium alginate or hydroxypropylmethyl cellulose, HPMC) to control drug release. The main objective was to investigate how the pharmacokinetic profile of the model drug could be modified by altering the proportion of the drug between the core and the coat. The effect of the amount of the polymer in the coat was also studied. Bioavailability tests were carried out on healthy volunteers. In the absorption curves of the tablets containing 50%, 67% and 80% of the drug in the core and 180 mg HPMC in the coat a bimodal profile was observed. No bimodal release pattern in the in vitro dissolution studies was found. If the whole dose was incorporated in the core the absorption curve has only one clear t(max) value at about 10 h. Doubling the amount of HPMC in the coat dramatically decreased drug absorption. It was concluded that, if a slightly reduced t(max)-value was required, the viscosity grade of HPMC used should be lowered.

Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

PubMed Central

Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

2017-01-01

Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique II. In vitro drug release studies and release mechanisms.

PubMed

Cheboyina, Sreekhar; Wyandt, Christy M

2008-07-09

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.

Modification of Sodium Release Using Porous Corn Starch and Lipoproteic Matrix.

PubMed

Christina, Josephine; Lee, Youngsoo

2016-04-01

Excessive sodium consumption can result in hypertension, diabetes, heart diseases, stroke, and kidney diseases. Various chips and extruded snacks, where salt is mainly applied on the product surface, accounted for almost 56% of snacks retail sales in 2010. Hence, it is important to target sodium reduction for those snack products. Past studies had shown that modifying the rate-release mechanism of sodium is a promising strategy for sodium reduction in the food industry. Encapsulation of salt can be a possible technique to control sodium release rate. Porous corn starch (PCS), created by enzymatic treatment and spray drying and lipoproteic matrix, created by gelation and freeze drying, were evaluated as carriers for controlled sodium release targeting topically applied salts. Both carriers encapsulated salt and their in vitro sodium release profiles were measured using a conductivity meter. The sodium release profiles of PCS treated with different enzymatic reaction times were not significantly different. Protein content and fat content altered sodium release profile from the lipoproteic matrix. The SEM images of PCS showed that most of the salt crystals coated the starch instead of being encapsulated in the pores while the SEM images and computed tomography scan of lipoproteic matrix showed salt dispersed throughout the matrix. Hence, PCS was found to have limitations as a sodium carrier as it could not effectively encapsulate salt inside its pores. The lipoproteic matrix was found to have a potential as a sodium carrier as it could effectively encapsulate salt and modify the sodium release profile. © 2016 Institute of Food Technologists®

Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

PubMed

Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

2015-12-30

The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

Not all GMOs are crop plants: non-plant GMO applications in agriculture.

PubMed

Hokanson, K E; Dawson, W O; Handler, A M; Schetelig, M F; St Leger, R J

2014-12-01

Since tools of modern biotechnology have become available, the most commonly applied and often discussed genetically modified organisms are genetically modified crop plants, although genetic engineering is also being used successfully in organisms other than plants, including bacteria, fungi, insects, and viruses. Many of these organisms, as with crop plants, are being engineered for applications in agriculture, to control plant insect pests or diseases. This paper reviews the genetically modified non-plant organisms that have been the subject of permit approvals for environmental release by the United States Department of Agriculture/Animal and Plant Health Inspection Service since the US began regulating genetically modified organisms. This is an indication of the breadth and progress of research in the area of non-plant genetically modified organisms. This review includes three examples of promising research on non-plant genetically modified organisms for application in agriculture: (1) insects for insect pest control using improved vector systems; (2) fungal pathogens of insects to control insect pests; and (3) virus for use as transient-expression vectors for disease control in plants.

Preliminary assessment of framework conditions for release of genetically modified mosquitoes in Burkina Faso.

PubMed

De Freece, Chenoa; Paré Toé, Léa; Esposito, Fulvio; Diabaté, Abdoulaye; Favia, Guido

2014-09-01

Genetically modified mosquitoes (GMMs) are emerging as a measure to control mosquito-borne diseases, but before any genetically modified organisms (GMOs) are released into the environment, it is imperative to establish regulatory standards incorporating public engagement. A previous project in Burkina Faso introduced a type of genetically modified cotton [Bacillus thuringiensis (Bt)] cotton) that produces insecticide, and incorporated policies on public engagement. We explored the perspectives of Burkinabè (citizens of Burkina Faso) on bio-agricultural exposure to GMOs and their receptiveness to the use of GMOs. Interviews were conducted in a village (Bondoukuy) and with representatives from stakeholder organizations. The population may be very receptive to the use of GMMs against malaria, but may voice unfounded concerns that GMMs can transmit other diseases. It is important to constantly supply the population with correct and factual information. Investigating the application of Burkina Faso's biotechnology policies with regard to Bt cotton has shown that it may be conceivable in the future to have open discussions about the merits of GMM release. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Urea encapsulation in modified starch matrix for nutrients retention

NASA Astrophysics Data System (ADS)

Naz, Muhammad Yasin; Sulaiman, Shaharin Anwar; Ariff, Mohd. Hazwan Bin Mohd.; Ariwahjoedi, Bambang

2014-10-01

It has been estimated that 20-70% of the used urea goes to the environment via leaching, nitrification and volatilization which not only harms the environment but also reduces the urea efficiency. By coating the urea granules, the farmers can achieve high urea performance through controlling the excess release of nitrogen. Up until now, different materials have been tested for nutrients retention. However, most of them are either expensive or unfriendly to the environment. Being cheap and biodegradable materials, the starches may also be used to coat the urea fertilizer for controlling the nutrients release. However, the pure starches do not meet the standards set by many industrial processes due to their slow tacking and too low viscosities and should be modified for getting smooth, compact and mechanically stronger coatings. In these studies, the tapioca starch was modified by reacting it with urea and different masses of borax. The prepared solutions were used to coat the urea granules of 3.45 mm average diameter. Different volumes (1, 1.5 and 2 mL) of each solution were used to coat 30 g of urea fluidized above the minimum level of fluidization. It was noticed that the coating thickness, percent coating, dissolution rate and percent release follow an increasing trend with an increase of solution volume; however, some random results were obtained while investigating the solution volume effects on the percent release. It was seen that the nutrients percent release over time increases with an increase in solution volume from 1 to 1.5 mL and thereafter reaches to a steady state. It confirms that the 1.5 mL of solution for 30 g urea samples will give the optimized coating results.

Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

PubMed

Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

2017-09-01

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix.

PubMed

Gerner, Peter; Wang, Chi-Fei; Lee, Byung-Sang; Suzuki, Suzuko; Degirolami, Umberto; Gandhi, Ankur; Knaack, David; Strichartz, Gary

2010-07-01

Nerve blocks of long duration are often desirable in perioperative and postoperative situations. The relationship between the duration of such blocks and the rate at which a local anesthetic is released is important to know for developing a localized drug delivery system that will optimize block duration. Lidocaine concentration was varied in 1 series of formulations (OSB-L) containing a constant amount of release rate modifier. In another series (OST-R), the release rate modifier was varied while the lidocaine content was held constant. Release kinetics were measured in vitro and correlated to the in vivo duration of antinociceptive and motor block effects when the formulation was implanted next to the rat sciatic nerve. In parallel studies, rats receiving different formulations of slow-release lidocaine were fixed by intracardiac perfusion with 4% paraformaldehyde and nerve-muscle tissue taken for histopathological analysis. In this study, we have demonstrated that the most important variable for effecting functional nerve block, i.e., the blockade of impulses in the relevant fibers of the sciatic nerve, is the rate of lidocaine release at that time. For the OSB-L formulations (lidocaine concentrations of 1.875%, 3.75%, 7.5%, and 15% at a constant release rate modifier of 5%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 0.91 +/- 0.28 and 1.75 +/- 0.61 mg/h, respectively. For the OST-R formulations (16% lidocaine with release rate modifier concentrations of 1.875%, 3.75%, 7.5%, and 15%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 2.33 +/- 1.39 and 4.34 +/- 1.09 mg/h, respectively. The OSB-L formulations showed a dose-dependent increase in block duration proportional to an increase in initial lidocaine concentration, whereas the OST-R formulations showed a nonmonotonic relationship between release rate modifier concentration and block duration. The histopathological studies at 24 hours, 3, 5, or 7 days, and 4 weeks after the implantation revealed inflammatory reactions with degrees correlated with lidocaine content, but limited to the connective tissue and muscle immediately surrounding the implanted material. Despite these observed inflammatory reactions, nociceptive and motor block function returned to normal, preimplantation values in all animals. Increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block. However, decreasing the release rate per se does not give a proportional increase in block duration. Instead, there seems to be an optimal, intermediate release rate for achieving the maximum duration of block.

Simultaneous expression and transportation of insulin by supramolecular polysaccharide nanocluster

NASA Astrophysics Data System (ADS)

Zhang, Yu-Hui; Zhang, Ying-Ming; Zhao, Qi-Hui; Liu, Yu

2016-03-01

Drug/gene transportation systems with stimuli-responsive release behaviors are becoming research hotspots in biochemical and biomedical fields. In this work, a glucose-responsive supramolecular nanocluster was successfully constructed by the intermolecular complexation of phenylboronic acid modified β-cyclodextrin with adamantane modified polyethylenimine, which could be used as a biocompatible carrier for insulin and pCMV3-C-GFPSpark-Ins DNA which could express insulin co-delivery. Benefiting from the response capability of phenylboronic acid moiety toward glucose, the encapsulated insulin could be specifically released and the corresponding targeted DNA could efficiently express insulin in HepG2 cell, accompanied by the high-level insulin release in vitro. Our results demonstrate that the simultaneous insulin drug delivery and insulin gene transfection in a controlled mode may have great potential in the clinical diabetes treatments.

Stability Analysis of Distributed Engine Control Systems Under Communication Packet Drop (Postprint)

DTIC Science & Technology

2008-07-01

use, modify, reproduce, release, perform, display, or disclose the work. 14. ABSTRACT Currently, Full Authority Digital Engine Control ( FADEC ...based on a centralized architecture framework is being widely used for gas turbine engine control. However, current FADEC is not able to meet the...system (DEC). FADEC based on Distributed Control Systems (DCS) offers modularity, improved control systems prognostics and fault tolerance along with

Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine

PubMed Central

Mohana Raghava Srivalli, K.; Lakshmi, P.K.; Balasubramaniam, J.

2012-01-01

Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 23 full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 103 dyn/cm2 was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t90% at 6th and 12th hours, respectively. The “n” value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength. PMID:24109205

Mechanism for Tuning the Hydrophobicity of Microfibrillated Cellulose Films by Controlled Thermal Release of Encapsulated Wax

PubMed Central

Rastogi, Vibhore Kumar; Stanssens, Dirk; Samyn, Pieter

2014-01-01

Although films of microfibrillated cellulose (MFC) have good oxygen barrier properties due to its fine network structure, properties strongly deteriorate after absorption of water. In this work, a new approach has been followed for actively tuning the water resistance of a MFC fiber network by the inclusion of dispersed organic nanoparticles with encapsulated plant wax. The modified pulp suspensions have been casted into films and were subsequently cured at 40 to 220 °C. As such, static water contact angles can be specifically tuned from 120 to 150° by selection of the curing temperature in relation with the intrinsic transition temperatures of the modified pulp, as determined by thermal analysis. The appearance of encapsulated wax after curing was followed by a combination of morphological analysis, infrared spectroscopy and Raman mapping, showing balanced mechanisms of progressive release and migration of wax into the fiber network controlling the surface properties and water contact angles. Finally, the appearance of nanoparticles covered with a thin wax layer after complete thermal release provides highest hydrophobicity. PMID:28788241

A multifunctional β-CD-modified Fe3O4@ZnO:Er(3+),Yb(3+) nanocarrier for antitumor drug delivery and microwave-triggered drug release.

PubMed

Peng, Hongxia; Cui, Bin; Li, Guangming; Wang, Yingsai; Li, Nini; Chang, Zhuguo; Wang, Yaoyu

2015-01-01

We constructed a novel core-shell structured Fe3O4@ZnO:Er(3+),Yb(3+)@(β-CD) nanoparticles used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug etoposide (VP-16). The cavity of β-cyclodextrin is chemically inert, it can store etoposide molecules by means of hydrophobic interactions. The Fe3O4 core and ZnO:Er(3+),Yb(3+) shell functioned successfully for magnetic targeting and up-conversion fluorescence imaging, respectively. In addition, the ZnO:Er(3+),Yb(3+) shell acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the VP-16 release of 18% under microwave irradiation for 15 min outclass the 2% within 6h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. This material therefore promises to be a useful noninvasive, externally controlled drug-delivery system in cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system.

PubMed

Li, Qingpo; Li, Wei; Di, Haixiao; Luo, Lihua; Zhu, Chunqi; Yang, Jie; Yin, Xiaoyi; Yin, Hang; Gao, Jianqing; Du, Yongzhong; You, Jian

2018-05-10

The targeted drug delivery with the help of nanocarriers and the controlled drug release at the lesion sites are the most effective ways to enhance therapeutic efficacy and reduce side effects. Here, we built a light sensitive liposome (Her2-I&D-LSL) which was formed by a special phospholipid (PLsPC) and a hydrophobically modified photosensitizer (ICG-ODA). DOX was employed as the therapeutic drug, encapsulating in the internal phase of the liposome whose surface was modified by Her2 antibodies for recognizing tumor cells with high Her2 receptor expression. Mediated by NIR light, Her2-I&D-LSL was proved to generate sufficient ROS to realize PDT, which then triggered the release of DOX for combined chemotherapy. The ROS generation and DOX release were verified to be strictly controlled by NIR light and the proportion of ICG-ODA. Thanks to the mediation of Her2 receptor, the specific DOX release and the combination of PDT-chemotherapy triggered by NIR light, Her2-I&D-LSL showed a significant accumulation in MCF7 and SKOV3 tumors, thus leading to the strongest tumor growth inhibition effect compared to PDT alone (I-LSL) or chemotherapy alone (D-LSL). Her2-I&D-LSL also possessed a great biocompatibility due to the targeted treatment, holding promise for future cancer therapy in clinic. Copyright © 2018 Elsevier B.V. All rights reserved.

Xylan-Modified-Based Hydrogels with Temperature/pH Dual Sensitivity and Controllable Drug Delivery Behavior

PubMed Central

Kong, Wei-Qing; Gao, Cun-Dian; Hu, Shu-Feng; Ren, Jun-Li; Zhao, Li-Hong; Sun, Run-Cang

2017-01-01

Among the natural macromolecules potentially used as the scaffold material in hydrogels, xylan has aroused great interest in many fields because of its biocompatibility, low toxicity, and biodegradability. In this work, new pH and thermoresponsive hydrogels were prepared by the cross-linking polymerization of maleic anhydride-modified xylan (MAHX) with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) under UV irradiation to form MAHX-g-P(NIPAm-co-AA) hydrogels. The pore volume, the mechanical properties, and the release rate for drugs of hydrogels could be controlled by the degree of substitution of MAHX. These hydrogels were characterized by swelling ability, lower critical solution temperature (LCST), Fourier-transform infrared (FTIR), and SEM. Furthermore, the cumulative release rate was investigated for acetylsalicylic acid and theophylline, as well as the cytocompatibility MAHX-based hydrogels. Results showed that MAHX-based hydrogels exhibited excellent swelling–deswelling properties, uniform porous structure, and the temperature/pH dual sensitivity. In vitro, the cumulative release rate of acetylsalicylic acid for MAHX-based hydrogels was higher than that for theophylline, and in the gastrointestinal sustained drug release study, the acetylsalicylic acid release rate was extremely slow during the initial 3 h in the gastric fluid (24.26%), and then the cumulative release rate reached to 90.5% after sustained release for 5 h in simulated intestinal fluid. The cytotoxicity experiment demonstrated that MAHX-based hydrogels could promote cell proliferation and had satisfactory biocompatibility with NIH3T3 cells. These results indicated that MAHX-based hydrogels, as new drug carriers, had favorable behavior for intestinal-targeted drug delivery. PMID:28772664

A Comparative Evaluation of the Amount of Fluoride Release and Re-Release after Recharging from Aesthetic Restorative Materials: An in vitro Study.

PubMed

Bansal, Ruchika; Bansal, Tajinder

2015-08-01

To measure the amount of fluoride released and re released after recharging from various restorative materials: Conventional Glass Ionomer Cement (Fuji II), Light Cure Resin Modified GIC (Fuji II LC), Giomer (Beautifil II), Compomer (Dyract). Fifteen cylindrical specimens were prepared from each material. The specimens were immersed in 20 ml of deionized water. The amount of released fluoride was measured during the 1(st) day, 7(th) day and on the day15 by using specific fluoride electrode and an ion-analyser. After 15 days each material was divided into three Sub Groups of five samples each. Sub Group A served as control, Sub Group B was exposed to 2% NaF solution, Sub Group C to 1000ppm F toothpaste. The amount of fluoride re-released was measured during the 1(st) day, 7(th) day and on the day15 by using specific fluoride electrode and an ion-analyser. The results were statistically analysed using analysis of variance (one-way ANOVA) and Tukey Kramer multiple comparison tests (p≤0.05). Independent of the observation time period of the study the Conventional GIC released the highest amount of fluoride followed by RMGIC, Giomer and Compomer. The initial burst effect was seen with GIC'S but not with Giomer and Compomer. After topical fluoride application fluoride re release was highest in Sub Group B and GIC had a greater recharging ability followed by RMGIC, Giomer and Compomer. The fluoride re release was greatest on 1(st) day followed by rapid return to near exposure levels. From the study it was concluded that, the initial Fluoride release was highest from Conventional GIC followed by Resin Modified GIC, Giomer and Compomer. The Fluoride re release was high when recharging with professional regime (2% NaF) as compared to home regime (Toothpaste). Conventional GIC had a greater recharging ability followed by Resin Modified GIC, Giomer and Compomer.

Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL

PubMed Central

Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

2011-01-01

The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO3) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO3 and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO3 and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism. PMID:22171304

Effects of N-vinylcaprolactam containing polyelectrolytes on hardness, fluoride release and water sorption of conventional glass ionomers.

PubMed

Moshaverinia, Alireza; Ansari, Sahar; Roohpour, Nima; Reshad, Mamaly; Schricker, Scott R; Chee, Winston Wl

2011-05-01

N-vinylcaprolactam (NVC) containing glass ionomers are promising dental restorative materials with improved mechanical properties; however, little information is available on other physical properties of this type of modified glass ionomer, especially their water sorption, fluoride releasing properties and microhardness. The purpose of this study was to investigate the effects of NVC-containing polyelectrolytes on microhardness, fluoride release and water sorption of conventional glass ionomer cements (GIC). The terpolymer of acrylic acid (AA), itaconic acid (IA) and N-vinylcaprolactam (NVC) with 8:1:1 and 7:1:2 (AA: IA: NVC) molar ratios was synthesized by free radical polymerization and characterized using 1H-NMR and FTIR. Experimental GIC specimens were made from a 50% solution of the synthesized terpolymer with Fuji IX powder in a 3.6:1 P/L ratio. Specimens were mixed and fabricated at room temperature. Vickers hardness was determined using a microhardness tester. Water sorption and fluoride releasing properties were also investigated. Commercial Fuji IX was used as the control group. All specimens were first conditioned in distilled water at 37°C for 1 day up to 1 month. Results for the experimental GIC were compared with the control group, using 1-way and 2-way ANOVA and the Tukey multiple range test (α=.05). The NVC-modified GIC exhibited higher mean values of Vickers hardness numbers (VHN). However, the data exhibited no statistically significant differences between the experimental and control groups. The experimental cement (TP2) absorbed significantly more water than the control group (P<.034). Additionally, NVC-containing specimens showed comparable fluoride releasing properties with almost the same fluoride burst and continued fluoride release from the bulk of the material. It was concluded that a hydrophilic monomer such as NVC might be able to increase the water sorption and decrease the amount of initial fluoride release of the glass ionomers. Hydrophilic monomer such as NVC might be able to increase the water sorption and decrease the amount of initial fluoride release of the glass ionomers. Copyright © 2011 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Osmotic Drug Delivery System as a Part of Modified Release Dosage Form

PubMed Central

Keraliya, Rajesh A.; Patel, Chirag; Patel, Pranav; Keraliya, Vipul; Soni, Tejal G.; Patel, Rajnikant C.; Patel, M. M.

2012-01-01

Conventional drug delivery systems are known to provide an immediate release of drug, in which one can not control the release of the drug and can not maintain effective concentration at the target site for longer time. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semipermeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. The historical development of osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull system. Recent advances include development of the controlled porosity osmotic pump, and systems based on asymmetric membranes. This paper highlights the principle of osmosis, materials used for fabrication of pumps, types of pumps, advantages, disadvantages, and marketed products of this system. PMID:22852100

Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.

PubMed

Weigel, Marianne; Hahner, Stefanie; Sherlock, Mark; Agha, Amar; Behan, Lucy Ann; Stewart, Paul M; Arlt, Wiebke; Beier, Daniela; Frey, Kathrin; Zopf, Kathrin; Quinkler, Marcus

2017-04-01

Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet. Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone. Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40-20-0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included. Serum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol. Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l; P = 0·03) resulting in a generally lower AUC (98 ± 21 vs 149 ± 37 nmol h/l; P = 0·02). 40-20-0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment. © 2017 John Wiley & Sons Ltd.

Evaluation of sticky traps for adult Aedes mosquitoes in Malaysia: a potential monitoring and surveillance tool for the efficacy of control strategies.

PubMed

Roslan, Muhammad Aidil; Ngui, Romano; Vythilingam, Indra; Sulaiman, Wan Yusoff Wan

2017-12-01

The present study compared the performance of sticky traps in order to identify the most effective and practical trap for capturing Aedes aegypti and Aedes albopictus mosquitoes. Three phases were conducted in the study, with Phase 1 evaluating the five prototypes (Models A, B, C, D, and E) of sticky trap release-and-recapture using two groups of mosquito release numbers (five and 50) that were released in each replicate. Similarly, Phase 2 compared the performance between Model E and the classical ovitrap that had been modified (sticky ovitrap), using five and 50 mosquito release numbers. Further assessment of both traps was carried out in Phase 3, in which both traps were installed in nine sampling grids. Results from Phase 1 showed that Model E was the trap that recaptured higher numbers of mosquitoes when compared to Models A, B, C, and D. Further assessment between Model E and the modified sticky ovitrap (known as Model F) found that Model F outperformed Model E in both Phases 2 and 3. Thus, Model F was selected as the most effective and practical sticky trap, which could serve as an alternative tool for monitoring and controlling dengue vectors in Malaysia. © 2017 The Society for Vector Ecology.

Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers

PubMed Central

Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin

2018-01-01

Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h. PMID:29565280

Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers.

PubMed

Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin; Yu, Deng-Guang

2018-03-22

Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.

PubMed

Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J

2011-04-01

The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.

RES-loaded pegylated CS NPs: for efficient ocular delivery.

PubMed

Pandian, Saravanakumar; Jeevanesan, Vinoth; Ponnusamy, Chandrasekar; Natesan, Subramanian

2017-02-01

The objective of this study is to develop resveratrol (RES) loaded polyethylene glycols (PEGs) modified chitosan (CS) nanoparticles (NPs) by ionic gelation method for the treatment of glaucoma. While increasing the concentration of PEG, the particle size and polydispersity index of the formulations increased. Entrapment efficiency and RES loading (RL) of NPs decreased while increasing PEG concentration. The in vitro release of NPs showed an initial burst release of RES (45%) followed by controlled release. Osmolality of formulations revealed that the prepared NPs were iso-osmolar with the tear. Ocular tolerance of the NPs was evaluated using hen's egg test on the chorioallantoic membrane and it showed that the NPs were non-irritant. RES-loaded PEG-modified CS NPs shows an improved corneal permeation compared with RES dispersion. Fluorescein isothiocyanate loaded CS NPs accumulated on the surface of the cornea but the PEG-modified CS NPs crossed the cornea and reached retinal choroid. RES-loaded PEG-modified CS NPs reduced the intra-ocular pressure (IOP) by 4.3 ± 0.5 mmHg up to 8 h in normotensive rabbits. These results indicate that the developed NPs have efficient delivery of RES to the ocular tissues and reduce the IOP for the treatment of glaucoma.

Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

PubMed

Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

2011-01-01

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

Controllable synthesis of a novel magnetic core-shell nanoparticle for dual-modal imaging and pH-responsive drug delivery

NASA Astrophysics Data System (ADS)

Xu, Chen; Zhang, Cheng; Wang, Yingxi; Li, Liu; Li, Ling; Whittaker, Andrew K.

2017-12-01

In this study, novel magnetic core-shell nanoparticles Fe3O4@La-BTC/GO have been synthesized by the layer-by-layer self-assembly (LBL) method and further modified by attachment of amino-modified PEG chains. The nanoparticles were thoroughly characterized by x-ray diffraction, FTIR, scanning electron microscopy and transmission electron microscopy. The core-shell structure was shown to be controlled by the LBL method. The drug loading of doxorubicin (DOX) within the Fe3O4@La-BTC/GO-PEG nanoparticles with different numbers of deposited layers was investigated. It was found that DOX loading increased with increasing number of metal organic framework coating layers, indicating that the drug loading can be controlled through the controllable LBL method. Cytotoxicity assays indicated that the Fe3O4@La-BTC/GO-PEG nanoparticles were biocompatible. The DOX was released rapidly at pH 3.8 and pH 5.8, but at pH 7.4 the rate and extent of release was greatly attenuated. The nanoparticles therefore demonstrate an excellent pH-triggered drug release. In addition, the particles could be tracked by magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI). A clear dose-dependent contrast enhancement in T 2-weighted MR images and fluorescence images indicate the potential of these nanoparticles as dual-mode MRI/FOI contrast agents.

Fabrication of graphene oxide-modified chitosan for controlled release of dexamethasone phosphate

NASA Astrophysics Data System (ADS)

Sun, Huanghui; Zhang, Lingfan; Xia, Wei; Chen, Linxiao; Xu, Zhizhen; Zhang, Wenqing

2016-07-01

Functionalized graphene oxide with its unique physical and chemical properties is widely applied in biomaterials, especially in drug carrier materials. In the past few years, a number of different drugs have been loaded on functionalized graphene oxide via π-π stacking and hydrophobic interactions. The present report described a new approach, dexamethasone phosphate successfully loaded onto graphene oxide-chitosan nanocomposites as drug carrier materials by covalent bonding of phosphate ester linkage. Compared with the graphene oxide-chitosan nanocomposites that dexamethasone phosphate was loaded on via simple physical attachment, covalently linked composites as drug carrier materials were more biocompatible which effectively reduced the burst release of drug, and controlled the release of drug in different pH conditions.

CRRES combined radiation and release effects satellite program

NASA Technical Reports Server (NTRS)

Giles, B. L. (Compiler); Mccook, M. A. (Compiler); Mccook, M. W. (Compiler); Miller, G. P. (Compiler)

1995-01-01

The various regions of the magnetosphere-ionosphere system are coupled by flows of charged particle beams and electromagnetic waves. This coupling gives rise to processes that affect both technical and non-technical aspects of life on Earth. The CRRES Program sponsored experiments which were designed to produce controlled and known input to the space environment and the effects were measured with arrays of diagnostic instruments. Large amounts of material were used to modify and perturb the environment in a controlled manner, and response to this was studied. The CRRES and PEGSAT satellites were dual-mission spacecraft with a NASA mission to perform active chemical-release experiments, grouped into categories of tracer, modification, and simulation experiments. Two sounding rocket chemical release campaigns completed the study.

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

PubMed Central

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Effects of incorporation of nano-fluorapatite or nano-fluorohydroxyapatite on a resin-modified glass ionomer cement.

PubMed

Lin, Jun; Zhu, Jiajun; Gu, Xiaoxia; Wen, Wenjian; Li, Qingshan; Fischer-Brandies, Helge; Wang, Huiming; Mehl, Christian

2011-03-01

This study aimed to investigate the fluoride release properties and the effect on bond strength of two experimental adhesive cements. Synthesized particles of nano-fluorapatite (nano-FA) or nano-fluorohydroxyapatite (nano-FHA) were incorporated into a resin-modified glass ionomer cement (Fuji Ortho LC) and characterized using X-ray diffraction and scanning electron microscopy. Blocks with six different concentrations of nano-FA or nano-FHA were manufactured and their fluoride release properties evaluated by ultraviolet spectrophotometry. The unaltered glass ionomer cement Fuji Ortho LC (GC, control) and the two experimental cements with the highest fluoride release capacities (nano-FA+Fuji Ortho LC (GFA) and nano-FHA+Fuji Ortho LC (GFHA)) were used to bond composite blocks and orthodontic brackets to human enamel. After 24 h water storage all specimens were debonded, measuring the micro-tensile bond strength (μTBS) and the shear bond strength (SBS), respectively. The optimal concentration of added nano-FA and nano-FHA for maximum fluoride release was 25 wt.%, which nearly tripled fluoride release after 70 days compared with the control group. GC exhibited a significantly higher SBS than GFHA/GFA, with GFHA and GFA not differing significantly (P>0.05). The μTBS of GC and GFA were significantly higher than that of GFHA (P≤0.05). The results seem to indicate that the fluoride release properties of Fuji Ortho LC are improved by incorporating nano-FA or nano-FHA, simultaneously maintaining a clinically sufficient bond strength when nano-FA was added. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ion-exchange and iontophoresis-controlled delivery of apomorphine.

PubMed

Malinovskaja, Kristina; Laaksonen, Timo; Kontturi, Kyösti; Hirvonen, Jouni

2013-04-01

The objective of this study was to test a drug delivery system that combines iontophoresis and cation-exchange fibers as drug matrices for the controlled transdermal delivery of antiparkinsonian drug apomorphine. Positively charged apomorphine was bound to the ion-exchange groups of the cation-exchange fibers until it was released by mobile counter-ions in the external solution. The release of the drug was controlled by modifying either the fiber type or the ionic composition of the external solution. Due to high affinity of apomorphine toward the ion-exchanger, a clear reduction in the in vitro transdermal fluxes from the fibers was observed compared to the respective fluxes from apomorphine solutions. Changes in the ionic composition of the donor formulations affected both the release and iontophoretic flux of the drug. Upon the application of higher co-ion concentrations or co-ions of higher valence in the donor formulation, the release from the fibers was enhanced, but the iontophoretic steady-state flux was decreased. Overall, the present study has demonstrated a promising approach using ion-exchange fibers for controlling the release and iontophoretic transdermal delivery of apomorphine. Copyright © 2012 Elsevier B.V. All rights reserved.

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

PubMed

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Encapsulation of an adamantane-doxorubicin prodrug in pH-responsive polysaccharide capsules for controlled release.

PubMed

Luo, Guo-Feng; Xu, Xiao-Ding; Zhang, Jing; Yang, Juan; Gong, Yu-Hui; Lei, Qi; Jia, Hui-Zhen; Li, Cao; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2012-10-24

Supramolecular microcapsules (SMCs) with the drug-loaded wall layers for pH-controlled drug delivery were designed and prepared. By using layer-by-layer (LbL) technique, the SMCs were constructed based on the self-assembly between polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft-β-CD (CMD-g-β-CD) on CaCO(3) particles via host-guest interaction. Simultaneously, adamantine-modified doxorubicin (AD-Dox) was also loaded on the LbL wall via host-guest interaction. The in vitro drug release study was carried out at different pHs. Because the AD groups were linked with PAD (PAD-g-AD) or Dox (AD-Dox) by pH-cleavable hydrazone bonds, AD moieties can be removed under the weak acidic condition, leading to destruction of SMCs and release of Dox. The pH-controlled drug release can enhance the uptake by tumor cells and thus achieve improved cancer therapy efficiency.

Spectroscopic Characterization and Nanosafety of Ag-Modified Antibacterial Leather and Leatherette.

PubMed

Sportelli, Maria Chiara; Picca, Rosaria Anna; Paladini, Federica; Mangone, Annarosa; Giannossa, Lorena Carla; Franco, Cinzia Di; Gallo, Anna Lucia; Valentini, Antonio; Sannino, Alessandro; Pollini, Mauro; Cioffi, Nicola

2017-07-29

The development of antibacterial coatings is of great interest from both industry and the consumer's point of view. In this study, we characterized tanned leather and polyurethane leatherette, typically employed in the automotive and footwear industries, which were modified by photo-deposition of antibacterial silver nanoparticles (AgNPs). Material surface chemical composition was investigated in detail by X-ray photoelectron spectroscopy (XPS). The material's antibacterial capability was checked against Escherichia coli and Staphylococcus aureus , as representative microorganisms in cross transmissions. Due to the presence of silver in a nanostructured form, nanosafety issues were considered, as well. Ionic release in contact media, as well as whole nanoparticle release from treated materials, were quantitatively evaluated, thus providing specific information on potential product nanotoxicity, which was further investigated through cytocompatibility MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, also after surface abrasion of the materials. The proved negligible nanoparticle release, as well as the controlled release of antibacterial ions, shed light on the materials' potentialities, in terms of both high activity and safety.

Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

PubMed

Kokuryo, Daisuke; Nakashima, Seiji; Ozaki, Fuminori; Yuba, Eiji; Chuang, Kai-Hsiang; Aoshima, Sadahito; Ishizaka, Yukihito; Saga, Tsuneo; Kono, Kenji; Aoki, Ichio

2015-01-01

Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Spectroscopic Characterization and Nanosafety of Ag-Modified Antibacterial Leather and Leatherette

PubMed Central

Mangone, Annarosa; Di Franco, Cinzia; Gallo, Anna Lucia; Valentini, Antonio; Sannino, Alessandro

2017-01-01

The development of antibacterial coatings is of great interest from both industry and the consumer’s point of view. In this study, we characterized tanned leather and polyurethane leatherette, typically employed in the automotive and footwear industries, which were modified by photo-deposition of antibacterial silver nanoparticles (AgNPs). Material surface chemical composition was investigated in detail by X-ray photoelectron spectroscopy (XPS). The material’s antibacterial capability was checked against Escherichia coli and Staphylococcus aureus, as representative microorganisms in cross transmissions. Due to the presence of silver in a nanostructured form, nanosafety issues were considered, as well. Ionic release in contact media, as well as whole nanoparticle release from treated materials, were quantitatively evaluated, thus providing specific information on potential product nanotoxicity, which was further investigated through cytocompatibility MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, also after surface abrasion of the materials. The proved negligible nanoparticle release, as well as the controlled release of antibacterial ions, shed light on the materials’ potentialities, in terms of both high activity and safety. PMID:28758912

Oil and drug control the release rate from lyotropic liquid crystals.

PubMed

Martiel, Isabelle; Baumann, Nicole; Vallooran, Jijo J; Bergfreund, Jotam; Sagalowicz, Laurent; Mezzenga, Raffaele

2015-04-28

The control of the diffusion coefficient by the dimensionality d of the structure appears as a most promising lever to efficiently tune the release rate from lyotropic liquid crystalline (LLC) phases and dispersed particles towards sustained, controlled and targeted release. By using phosphatidylcholine (PC)- and monolinoleine (MLO)-based mesophases with various apolar structural modifiers and water-soluble drugs, we present a comprehensive study of the dimensional structural control of hydrophilic drug release, including 3-d bicontinuous cubic, 2-d lamellar, 1-d hexagonal and 0-d micellar cubic phases in excess water. We investigate how the surfactant, the oil properties and the drug hydrophilicity mitigate or even cancel the effect of structure variation on the drug release rate. Unexpectedly, the observed behavior cannot be fully explained by the thermodynamic partition of the drug into the lipid matrix, which points out to previously overlooked kinetic effects. We therefore interpret our results by discussing the mechanism of structural control of the diffusion rate in terms of drug permeation through the lipid membrane, which includes exchange kinetics. A wide range of implications follow regarding formulation and future developments, both for dispersed LLC delivery systems and topical applications in bulk phase. Copyright © 2015 Elsevier B.V. All rights reserved.

Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

NASA Astrophysics Data System (ADS)

Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng

2015-01-01

The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

Role of different types of Ca2+ channels and a reticulum-like Ca2+ pump in neurotransmitter release.

PubMed

Fossier, P; Baux, G; Tauc, L

1993-01-01

The factors controlling the Ca2+ concentration directly responsible for triggering acetylcholine (ACh) release were investigated at an identified neuro-neuronal synapse of the Aplysia buccal ganglion. The types of presynaptic voltage-gated Ca2+ channels associated with transmitter release were determined by using selective blockers such as nifedipine, omega-conotoxin and a partially purified extract from the venom of a funnel web spider (FTx). L-type, N-type and P-type Ca2+ channels are present in the presynaptic neuron. The influx of Ca2+ through both N- and P-types induces the release of ACh whereas Ca2+ flowing through L-type channels modulates the duration of the presynaptic action potential by controlling the Ca(2+)-dependent K+ current. tBuBHQ, a blocker of the reticulum Ca2+ pump, induces a potentiation of evoked release without modifying the presynaptic Ca2+ influx. This seems to indicate that a part of the Ca2+ entering the presynaptic terminal through N- and P-type Ca2+ channels is sequestered in a presynaptic reticulum-like Ca2+ buffer preventing these ions from contributing to ACh release. To exert its control, this Ca2+ buffer must be located close to both the presynaptic Ca2+ channels and the transmitter release mechanism.

Potential Application of Silica Mineral from Dieng Mountain in Agriculture Sector to Control the Release Rate of Fertilizer Elements

NASA Astrophysics Data System (ADS)

Solihin; Mursito, Anggoro Tri; Dida, Eki N.; Erlangga, Bagus D.; Widodo

2017-07-01

Silica mineral, which comes along with geothermal fluid in Dieng, is a product of erosion, decomposition and dissolution of silicon oxide based mineral, which is followed by precipitation to form silica mineral. This silica cell structure is non crystalline, and it contains 85,60 % silicon oxide, 6.49 volatile elements, and also other oxide elements. Among the direct potential application of this silica is as raw material in slow release fertilizer. Silica in compacted slow release fertilizer is able control the release rate of fertilizer elements. Two type of slow release fertilizer has been made by using silica as the matrix in these slow release fertilizer. The first type is the mixing of ordinary solid fertilizer with Dieng silica, whereas the second one is the mixing of disposal leach water with Dieng silica. The release test shows that both of these modified fertilizers have slow release fertilizer characteristic. The release rate of fertilizer elements (magnesium, potassium, ammonium, and phosphate) can be significantly reduced. The addition of kaolin in the first type of slow release fertilizer makes the release rate of fertilizer elements can be more slowed down. Meanwhile in the second type of slow release fertilizer, the release rate is determined by ratio of silica/hydrogel. The lowest release rate is achieved by sample that has highest ratio of silica/hydrogel.

Graft polymerization of guar gum with acryl amide irradiated by microwaves for colonic drug delivery.

PubMed

Shahid, Muhammad; Bukhari, Shazia Anwer; Gul, Yousra; Munir, Hira; Anjum, Fozia; Zuber, Mohammad; Jamil, Tahir; Zia, Khalid Mahmood

2013-11-01

This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria

PubMed Central

2014-01-01

Background The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria. Methods The sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered. Results All participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support. Conclusions Although a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release. PMID:24758165

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria.

PubMed

Okorie, Patricia N; Marshall, John M; Akpa, Onoja M; Ademowo, Olusegun G

2014-04-23

The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria. The sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered. All participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support. Although a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release.

Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

PubMed

Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

2017-07-26

Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

Comparison of leaching characteristics of heavy metals in APC residue from an MSW incinerator using various extraction methods.

PubMed

Chiang, Kung-Yuh; Tsai, Chen-Chiu; Wang, Kuen-Sheng

2009-01-01

This study investigates four extraction methods (water extraction, toxicity characteristics leaching procedure (TCLP), modified TCLP with pH control, and sequential chemical extraction (SCE)), each representing different liquid-to-solid (L/S) ratios, pH controls, and types of leachant, and their effects on the leaching concentration of heavy metals in municipal solid waste (MSW) incinerator air pollution control (APC) residue. The results indicated that for extraction with distilled water, the heavy metal leaching concentration (mg/l) decreased with L/S ratio, but the amount of heavy metal released (AHMR), defined as the leached amount of heavy metals to the weight of the tested sample (mg/kg), increased with an increase in L/S ratio, in the range of 2-100. The results also showed that both the leaching concentration and the amount of released metals were strongly pH-dependent in the TCLP and modified TCLP tests. In the case of pHs lower than 6.5, the leaching concentrations of Cd, Pb, Cu, Zn, and Cr decreased with an increase in pH. As pH increased higher than 6.5, Cr and Zn were almost insoluble. Meanwhile, Cd and Cu also showed a similar trend but at pHs of 8.5 and 7.5, respectively. Due to the nature of amphoteric elements, in the case of pHs higher than 7, the Pb leaching concentration increased with increasing pH. In modified TCLP tests with the pH value controlled at the same level as in the SCE test, the heavy metal speciation approached the extractable carbonate bound fraction by the SCE. Both amounts of targeted metals leached from the SCE and modified TCLP tests were much higher than those for the regular TCLP and water extraction tests.

Sustained Release of Naproxen in a New Kind Delivery System of Carbon Nanotubes Hydrogel

PubMed Central

Peng, Xiahui; Zhuang, Qiang; Peng, Dongming; Dong, Qiuli; Tan, Lini; Jiao, Feipeng; Liu, Linqi; Liu, jingyu; Zhao, Chenxi; Wang, Xiaomei

2013-01-01

In this paper, carbon nanotubes (CNTs) were added into chitosan (CS) hydrogels in the form of chitosan modified CNTs (CS-CNTs) composites to prepare carbon nanotubes hydrogels (CNTs-GEL). The products, named CS-MWCNTs, were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs- GEL and pure chitosan hydrogels without CNTs (GEL), were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes. PMID:24523738

Open Field Release of Genetically Engineered Sterile Male Aedes aegypti in Malaysia

PubMed Central

Raduan, Norzahira; Kwee Wee, Lim; Hong Ming, Wong; Guat Ney, Teoh; Rahidah A.A., Siti; Salman, Sawaluddin; Subramaniam, Selvi; Nordin, Oreenaiza; Hanum A.T., Norhaida; Angamuthu, Chandru; Marlina Mansor, Suria; Lees, Rosemary S.; Naish, Neil; Scaife, Sarah; Gray, Pam; Labbé, Geneviève; Beech, Camilla; Nimmo, Derric; Alphey, Luke; Vasan, Seshadri S.; Han Lim, Lee; Wasi A., Nazni; Murad, Shahnaz

2012-01-01

Background Dengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods. However, this requires that lab-reared, modified mosquitoes be able to survive and disperse adequately in the field. Methodology/Principal Findings Adult male mosquitoes were released into an uninhabited forested area of Pahang, Malaysia. Their survival and dispersal was assessed by use of a network of traps. Two strains were used, an engineered ‘genetically sterile’ (OX513A) and a wild-type laboratory strain, to give both absolute and relative data about the performance of the modified mosquitoes. The two strains had similar maximum dispersal distances (220 m), but mean distance travelled of the OX513A strain was lower (52 vs. 100 m). Life expectancy was similar (2.0 vs. 2.2 days). Recapture rates were high for both strains, possibly because of the uninhabited nature of the site. Conclusions/Significance After extensive contained studies and regulatory scrutiny, a field release of engineered mosquitoes was safely and successfully conducted in Malaysia. The engineered strain showed similar field longevity to an unmodified counterpart, though in this setting dispersal was reduced relative to the unmodified strain. These data are encouraging for the future testing and implementation of genetic control strategies and will help guide future field use of this and other engineered strains. PMID:22970102

Encapsulation and delivery of food ingredients using starch based systems.

PubMed

Zhu, Fan

2017-08-15

Functional ingredients can be encapsulated by various wall materials for controlled release in food and digestion systems. Starch, as one of the most abundant natural carbohydrate polymers, is non-allergenic, GRAS, and cheap. There has been increasing interest of using starch in native and modified forms to encapsulate food ingredients such as flavours, lipids, polyphenols, carotenoids, vitamins, enzymes, and probiotics. Starches from various botanical sources in granular or amorphous forms are modified by chemical, physical, and/or enzymatic means to obtain the desired properties for targeted encapsulation. Other wall materials are also employed in combination with starch to facilitate some types of encapsulation. Various methods of crafting the starch-based encapsulation such as electrospinning, spray drying, antisolvent, amylose inclusion complexation, and nano-emulsification are introduced in this mini-review. The physicochemical and structural properties of the particles are described. The encapsulation systems can positively influence the controlled release of food ingredients in food and nutritional applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

PubMed

Fang, Jen-Hung; Chiu, Tsung-Lang; Huang, Wei-Chen; Lai, Yen-Ho; Hu, Shang-Hsiu; Chen, You-Yin; Chen, San-Yuan

2016-03-01

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue.

PubMed

Murray, Justine V; Jansen, Cassie C; De Barro, Paul

2016-01-01

In an effort to eliminate dengue, a successful technology was developed with the stable introduction of the obligate intracellular bacteria Wolbachia pipientis into the mosquito Aedes aegypti to reduce its ability to transmit dengue fever due to life shortening and inhibition of viral replication effects. An analysis of risk was required before considering release of the modified mosquito into the environment. Expert knowledge and a risk assessment framework were used to identify risk associated with the release of the modified mosquito. Individual and group expert elicitation was performed to identify potential hazards. A Bayesian network (BN) was developed to capture the relationship between hazards and the likelihood of events occurring. Risk was calculated from the expert likelihood estimates populating the BN and the consequence estimates elicited from experts. The risk model for "Don't Achieve Release" provided an estimated 46% likelihood that the release would not occur by a nominated time but generated an overall risk rating of very low. The ability to obtain compliance had the greatest influence on the likelihood of release occurring. The risk model for "Cause More Harm" provided a 12.5% likelihood that more harm would result from the release, but the overall risk was considered negligible. The efficacy of mosquito management had the most influence, with the perception that the threat of dengue fever had been eliminated, resulting in less household mosquito control, and was scored as the highest ranked individual hazard (albeit low risk). The risk analysis was designed to incorporate the interacting complexity of hazards that may affect the release of the technology into the environment. The risk analysis was a small, but important, implementation phase in the success of this innovative research introducing a new technology to combat dengue transmission in the environment.

Incorporation of amoxicillin-loaded organic montmorillonite into poly(ester-urethane) urea nanofibers as a functional tissue engineering scaffold.

PubMed

Yu, Kui; Zhu, Tonghe; Wu, Yu; Zhou, Xiangxiang; Yang, Xingxing; Wang, Juan; Fang, Jun; El-Hamshary, Hany; Al-Deyab, Salem S; Mo, Xiumei

2017-03-01

A dual drug-loaded system is a promising alternative for the sustained drug release system and skin tissue engineering. In this study, a natural sodium montmorillonite (Na-MMT) modified by cetyl trimethyl ammonium bromide (CTAB) was prepared as a carrier to load a model drug - amoxicillin (AMX), the modified organic montmorillonite (CTAB-OMMT) loaded with AMX was marked as AMX@CTAB-OMMT and was subsequently incorporated into poly(ester-urethane) urea (PEUU) and gelatin hybrid nanofibers via electrospinning, resulting in a new drug-loaded nanofibrous scaffold (AMX@CTAB-OMMT-PU75). The scanning electron microscopy (SEM) result showed that the fiber morphology did not change after the embedding of AMX@CTAB-OMMT. Meanwhile, there was a significant increase of mechanical properties for PEUU/Gelatin hybrid nanofibers (PU75) after the incorporation of AMX@CTAB-OMMT and CTAB-OMMT. Importantly, AMX@CTAB-OMMT-PU75 nanofibers showed a kind of sustained drug release property which could be justified reasonably for the controlled release of AMX depending on the various application. The sustained release property could be identified roughly by the result of antibacterial test. The anaphylactic reaction test proved that there was no any anaphylactic reaction or inflammation on the back of rat for AMX@CTAB-OMMT-PU75 nanofibers. Consequently, the prepared drug-loaded AMX@CTAB-OMMT-PU75 nanofibrous scaffold is a promising candidate for application in the skin tissue engineering field and controlled drug release system. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of magnesium ions release, biocorrosion, and hemocompatibility of MAO/PLLA-modified magnesium alloy WE42.

PubMed

Lu, Ping; Cao, Lu; Liu, Yin; Xu, Xinhua; Wu, Xiangfeng

2011-01-01

Magnesium alloys may potentially be applied as biodegradable metallic materials in cardiovascular stent. However, the high corrosion rate hinders its clinical application. In this study, a new approach was adopted to control the corrosion rate by fabricating a biocompatible micro-arc oxidation/poly-L-lactic acid (MAO/PLLA) composite coating on the magnesium alloy WE42 substrate and the biocompatibility of the modified samples was investigated. The scanning electronic microscope (SEM) images were used to demonstrate the morphology of the samples before and after being submerged in hanks solution for 4 weeks. The degradation was evaluated through the magnesium ions release rate and electrochemical impedance spectroscopy (EIS) test. The biocompatibility of the samples was demonstrated by coagulation time and hemolysis behavior. The result shows that the poly-L-lactic acid (PLLA) effectively improved the corrosion resistance by sealing the microcracks and microholes on the surface of the MAO coating. The modified samples had good compatibility. © 2010 Wiley Periodicals, Inc.

Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

PubMed

Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

2014-01-01

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

2015-02-01

This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of hybrid inorganic/organic nitric oxide-releasing silica nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Carpenter, Alexis Wells

Nitric oxide (NO) is an endogenously produced free radical involved in a number of physiological processes. Thus, much research has focused on developing scaffolds that store and deliver exogenous NO. Herein, the synthesis of N-diazeniumdiolate-modified silica nanoparticles of various physical and chemical properties for biomedical applications is presented. To further develop NO-releasing silica particles for antimicrobial applications, a reverse microemulsion synthesis was designed to achieve nanoparticles of distinct sizes and similar NO release characteristics. Decreasing scaffold size resulted in improved bactericidal activity against Pseudomonas aeruginosa. Confocal microscopy revealed that the improved efficacy resulted from faster particle-bacterium association kinetics. To broaden the therapeutic potential of NO-releasing silica particles, strategies to tune NO release characteristics were evaluated. Initially, surface hydrophobicity and NO release kinetics were tuned by grafting hydrocarbon- and fluorocarbon-based silanes onto the surface of N-diazeniumdiolate-modified particles. The addition of fluorocarbons resulted in a 10x increase in the NO release half-life. The addition of short-chained hydrocarbons to the particle surface increased their stability in hydrophobic electrospun polyurethanes. Although NO release kinetics were longer than that of unmodified particles, durations were still limited to <7 days. An alternative strategy for increasing NO release duration involved directly stabilizing the N-diazeniumdiolate using O2-protecting groups. O2-Methoxymethyl 1-(4-(3-(trimethoxysilyl)propyl))piperazin-1-yl)diazen-1-ium-1,2-diolate (MOM-Pip/NO) was grafted onto mesoporous silica nanoparticles to yield scaffolds with an NO payload of 2.5 μmol NO/mg and an NO release half-life of 23 d. Doping the MOM-Pip/NO-modified particles into resin composites yielded antibacterial NO-releasing dental restorative materials. A 3-log reduction in viable adhered Streptococcus mutans was observed with the MOM-Pip/NO-doped composites compared to undoped controls. The greater chemical flexibility of macromolecular scaffolds is a major advantage over LMW NO donors as it allows for the incorporation of multiple functionalities onto a single scaffold. To demonstrate this advantage, dual functional particles were synthesized by covalently binding quaternary ammonium (QA) functionalities to the surface of NO-releasing silica particles. The QA functionality proved more effective against Staphylococcus aureus than P. aeruginosa, and increasing alkyl chain length correlated with increased efficacy. Nitric oxide-releasing QA-functionalized particles were found to be more effective against S. aureus compared to monofunctional particles.

Clay-based Formulations to Reduce the Environmental Impact of the Herbicide Terbuthylazine

USDA-ARS?s Scientific Manuscript database

Controlled release formulations of pesticides are receiving increasing attention as a way to reduce the environmental impact of pesticides after their application to agricultural soils. Natural and modified clay minerals have been proved to be efficient adsorbents for many pesticides and, accordingl...

Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

2016-07-01

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

PubMed

Zou, Qin; Li, Junfeng; Niu, Lulu; Zuo, Yi; Li, Jidong; Li, Yubao

2017-09-01

The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization.

PubMed

de Toledo, Lucas de Alcântara Sica; Rosseto, Hélen Cássia; Ravani, Laura; Cortesi, Rita; Bruschi, Marcos Luciano

2016-01-01

Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release.

Fabrication and characterization of amine terminated poly(arylene ether sulfone) modified epoxy-carbon fiber composites

NASA Technical Reports Server (NTRS)

Cecere, James A.; Senger, James S.; Mcgrath, James E.; Steiner, Paul A.; Wong, Raymond S.

1987-01-01

Multifunctional epoxy resin networks were chemically modified with thermoplastic amine terminated poly(arylene ether sulfones) of controlled molecular weights. This system was then examined as both neat resin and as a matrix resin for carbon fiber composites. The neat resin displayed a significant increase in both fracture toughness and energy release rate values. This was attributed to the altered morphology, which could be varied from particles of polysulfone in an epoxy matrix to that of a quasi-continuous polysulfone phase.

Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

PubMed

Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

2017-03-15

As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Light activated nitric oxide releasing materials

NASA Astrophysics Data System (ADS)

Muizzi Casanas, Dayana Andreina

The ability to control the location and dosage of biologically active molecules inside the human body can be critical to maximizing effective treatment of cardiovascular diseases like angina. The current standard of treatment relies on the metabolism of organonitrate drugs into nitric oxide (NO), which are not specific, and also show problems with densitization with long-term use. There is a need then to create a treatment method that gives targeted release of NO. Metal-nitrosyl (M-NO) complexes can be used for delivery of NO since the release of NO can be controlled with light. However, the NO-releasing drug must be activated with red light to ensure maximum penetration of light through tissue. However, the release of NO from M-NO complexes with red-light activation is a significant challenge since the energy required to break the metal-NO bond is usually larger than the energy provided by red light. The goal of this project was to create red- sensitive, NO-releasing materials based on Ru-salen-nitrosyl compounds. Our approach was to first modify Ru salen complexes to sensitize the photochemistry for release of NO after red light irradiation. Next, we pursued polymerization of the Ru-salen complexes. We report the synthesis and quantitative photochemical characterization of a series of ruthenium salen nitrosyl complexes. These complexes were modified by incorporating electron donating groups in the salen ligand structure at key locations to increase electron density on the Ru. Complexes with either an --OH or --OCH3 substituent showed an improvement in the quantum yield of release of NO upon blue light irradiation compared to the unmodified salen. These --OH and --OCH3 complexes were also sensitized for NO release after red light activation, however the red-sensitive complexes were unstable and showed ligand substitution on the order of minutes. The substituted complexes remained sensitive for NO release, but only after blue light irradiation. The Ru-nitrosyl complexes could be regenerated by treatment of the complex with solutions of nitrite. Treatment of the exhaustively irradiated solutions with excess NO2- led to generation of a Ru-NO complex that was sensitive to blue light. Preliminary work on creating metallopolymers of Ru-salen-NO is also discussed.

41 CFR 102-37.465 - May a SASP modify or release any of the terms and conditions of donation?

Code of Federal Regulations, 2010 CFR

2010-07-01

... release any of the terms and conditions of donation? 102-37.465 Section 102-37.465 Public Contracts and... REGULATION PERSONAL PROPERTY 37-DONATION OF SURPLUS PERSONAL PROPERTY Donations to Public Agencies, Service... SASP modify or release any of the terms and conditions of donation? You may alter or grant releases...

41 CFR 102-37.465 - May a SASP modify or release any of the terms and conditions of donation?

Code of Federal Regulations, 2013 CFR

2013-07-01

... release any of the terms and conditions of donation? 102-37.465 Section 102-37.465 Public Contracts and... REGULATION PERSONAL PROPERTY 37-DONATION OF SURPLUS PERSONAL PROPERTY Donations to Public Agencies, Service... SASP modify or release any of the terms and conditions of donation? You may alter or grant releases...

41 CFR 102-37.465 - May a SASP modify or release any of the terms and conditions of donation?

Code of Federal Regulations, 2011 CFR

2011-01-01

... release any of the terms and conditions of donation? 102-37.465 Section 102-37.465 Public Contracts and... REGULATION PERSONAL PROPERTY 37-DONATION OF SURPLUS PERSONAL PROPERTY Donations to Public Agencies, Service... SASP modify or release any of the terms and conditions of donation? You may alter or grant releases...

41 CFR 102-37.465 - May a SASP modify or release any of the terms and conditions of donation?

Code of Federal Regulations, 2012 CFR

2012-01-01

... release any of the terms and conditions of donation? 102-37.465 Section 102-37.465 Public Contracts and... REGULATION PERSONAL PROPERTY 37-DONATION OF SURPLUS PERSONAL PROPERTY Donations to Public Agencies, Service... SASP modify or release any of the terms and conditions of donation? You may alter or grant releases...

41 CFR 102-37.465 - May a SASP modify or release any of the terms and conditions of donation?

Code of Federal Regulations, 2014 CFR

2014-01-01

... release any of the terms and conditions of donation? 102-37.465 Section 102-37.465 Public Contracts and... REGULATION PERSONAL PROPERTY 37-DONATION OF SURPLUS PERSONAL PROPERTY Donations to Public Agencies, Service... SASP modify or release any of the terms and conditions of donation? You may alter or grant releases...

Artificial neural networks in evaluation and optimization of modified release solid dosage forms.

PubMed

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-10-18

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

PubMed Central

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-01-01

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms. PMID:24300369

Magnetic high throughput screening system for the development of nano-sized molecularly imprinted polymers for controlled delivery of curcumin.

PubMed

Piletska, Elena V; Abd, Bashar H; Krakowiak, Agata S; Parmar, Anitha; Pink, Demi L; Wall, Katie S; Wharton, Luke; Moczko, Ewa; Whitcombe, Michael J; Karim, Kal; Piletsky, Sergey A

2015-05-07

Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low bioavailability, which could be improved by developing materials capable of binding and releasing drug in a controlled fashion. The present study describes the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs) for the controlled delivery of curcumin and their high throughput characterisation using microtitre plates modified with magnetic inserts. NanoMIPs were synthesised using functional monomers chosen with the aid of molecular modelling. The rate of release of curcumin from five polymers was studied under aqueous conditions and was found to correlate well with the binding energies obtained computationally. The presence of specific monomers was shown to be significant in ensuring effective binding of curcumin and to the rate of release obtained. Characterisation of the polymer particles was carried out using dynamic light scattering (DLS) technique and scanning electron microscopy (SEM) in order to establish the relationship between irradiation time and particle size. The protocols optimised during this study could be used as a blueprint for the development of nanoMIPs capable of the controlled release of potentially any compound of interest.

Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.

PubMed

Marrachelli, Vannina G; Centeno, José M; Miranda, Ignacio; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

2012-11-01

Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A(2) and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K(+) channel (K(ATP)), voltage-sensitive K(+) channels (K(V)) and TEA-sensitive K(+) channels (K(Ca)). Copyright © 2012 Elsevier Ltd. All rights reserved.

Fabrication of monodispersive nanoscale alginate-chitosan core-shell particulate systems for controlled release studies

NASA Astrophysics Data System (ADS)

Körpe, Didem Aksoy; Malekghasemi, Soheil; Aydın, Uğur; Duman, Memed

2014-12-01

Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core-shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 ± 10 and 60 ± 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 ± 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.

Nitric Oxide Releasing Coronary Stent: A New Approach Using Layer-by-Layer Coating and Liposomal Encapsulation.

PubMed

Elnaggar, Mahmoud A; Seo, Seong Ho; Gobaa, Samy; Lim, Kyung Seob; Bae, In-Ho; Jeong, Myung Ho; Han, Dong Keun; Joung, Yoon Ki

2016-11-01

The sustained or controlled release of nitric oxide (NO) can be the most promising approach for the suppression or prevention of restenosis and thrombosis caused by stent implantation. The aim of this study is to investigate the feasibility in the potential use of layer-by-layer (LBL) coating with a NO donor-containing liposomes to control the release rate of NO from a metallic stent. Microscopic observation and surface characterizations of LBL-modified stents demonstrate successful LBL coating with liposomes on a stent. Release profiles of NO show that the release rate is sustained up to 5 d. In vitro cell study demonstrates that NO release significantly enhances endothelial cell proliferation, whereas it markedly inhibits smooth muscle cell proliferation. Finally, in vivo study conducted with a porcine coronary injury model proves the therapeutic efficacy of the NO-releasing stents coated by liposomal LBL technique, supported by improved results in luminal healing, inflammation, and neointimal thickening except thrombo-resistant effect. As a result, all these results demonstrate that highly optimized release rate and therapeutic dose of NO can be achieved by LBL coating and liposomal encapsulation, followed by significantly efficacious outcome in vivo. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin.

PubMed

Cui, Yan-Na; Xu, Qing-Xing; Davoodi, Pooya; Wang, De-Ping; Wang, Chi-Hwa

2017-06-01

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin

PubMed Central

Cui, Yan-na; Xu, Qing-xing; Davoodi, Pooya; Wang, De-ping; Wang, Chi-Hwa

2017-01-01

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors. PMID:28552909

Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

PubMed

Aksoy, Senai; Yakin, Kayhan; Seyhan, Ayse; Oktem, Ozgur; Alatas, Cengiz; Ata, Baris; Urman, Bulent

2016-06-01

Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p < 0.001). However, the difference between the numbers of IVF cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

A hurricane modification process, applying a new technology tested for warm cloud seeding to produce artificial rains

NASA Astrophysics Data System (ADS)

Imai, T.; Martin, I.; Iha, K.

A Hurricane Modification Process with application of a new clean technology attested for seeding warm clouds with collector pure water droplets of controlled size to produce artificial rains in warm clouds is proposed to modify the hurricanes in order to avoid their formation or to modify the trajectory or to weaken hurricanes in action The Process is based on the time-dependent effects of cloud droplets microphysical processes for the formation and growth of the natural water droplets inside the clouds releasing large volumes of Aeolian energy to form the strong rotative upside air movements A new Paradigm proposed explain the strong and rotative winds created with the water droplets formation and grow process releasing the rotative Aeolian Energy in Tornados and Hurricanes This theory receive the Gold Medal Award of the Water Science in the 7th International Water Symposium 2005 in France Artificial seeding in the Process studies condensing a specified percentage of the water vapor to liquid water droplets where we observe the release of larges intensity of the Aeolian energy creates the hurricanes producing appreciable perturbations With they rotating strong wind created by the water droplets releasing Aeolian energy The Amplitudes of these winds are comparable to natural disasters Once this natural thermal process is completely understood artificial process to modify the hurricanes become scientifically possible to avoid them to happen or to deviate their trajectory or to weaken the already formed hurricanes In this work

Inorganically modified diatomite as a potential prolonged-release drug carrier.

PubMed

Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

2014-09-01

Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate).

PubMed

Alhusein, Nour; Blagbrough, Ian S; De Bank, Paul A

2012-12-01

We report the controlled release of tetracycline (Tet) HCl from a three-layered electrospun matrix for the first time. Five formulations of electrospun poly-ε-caprolactone (PCL) and poly(ethylene-co-vinyl acetate) (PEVA) have been designed, prepared as micro/nanofibre layers, and assayed for the controlled release of the clinically useful antibiotic Tet HCl with potential applications in wound healing and especially in complicated skin and skin-structure infections. Tet HCl was also chosen as a model drug possessing a good ultraviolet (UV) chromophore and capable of fluorescence together with limited stability. Tet HCl was successfully incorporated (essentially quantitatively at 3 %, w/w) and provided controlled release from multilayered electrospun matrices. The Tet HCl release test was carried out by a total immersion method on 2 × 2 cm(2) electrospun fibrous mats in Tris or phosphate-buffered saline heated to 37 °C. The formulation PCL/PEVA/PCL with Tet HCl in each layer gave a large initial (burst) release followed by a sustained release. Adding a third layer to the two-layered formulations led to release being sustained from 6 days to more than 15 days. There was no detectable loss of Tet chemical stability (as shown by UV and NMR) or bioactivity (as shown by a modified Kirby-Bauer disc assay). Using Tet HCl-sensitive bacteria, Staphylococcus aureus (ATCC 25923), the Tet HCl-loaded three-layered matrix formulations were still showing significantly higher antibacterial effects on days 4 and 5 than commercially available Antimicrobial Susceptibility Test Discs of Tet HCl. Electrospinning provides good encapsulation efficiency of Tet HCl within PCL/PEVA/PCL polymers in micro/nanofibre layers which display sustained antibiotic release.

pH-controlled doxorubicin anticancer loading and release from carbon nanotube noncovalently modified by chitosan: MD simulations.

PubMed

Rungnim, Chompoonut; Rungrotmongkol, Thanyada; Poo-Arporn, Rungtiva P

2016-11-01

In the present study, we describe here the pH condition activating doxorubicin (DOX) anticancer drugs loading and release over single-wall carbon nanotube (SWNT) non-covalently wrapped with chitosan (CS). The possibility of drug displacement on DOX/CS/SWNT nanocarrier was investigated using molecular dynamics simulations. The drug loading and release were monitored via displacement analysis and binding energy calculations. The simulated results clearly showed that the drugs well interacted with the CS/SWNT at physiological pH (pH 7.4), where CS was in the deprotonated form. Contrastingly, in weakly acidic environments (pH 5.0-6.5) which is a pH characteristics of certain cancer environments, the protonated CS became loosen wrapped around the SWNT and triggered drugs release as a result of charge-charge repulsion between CS and drug molecules. The obtained data fulfil the understanding at atomic level of drug loading and release controlled by pH-sensitive polymer, which might be useful for further cancer therapy researches. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane.

PubMed

Yu, Zhan; Yu, Min; Zhou, Zhimin; Zhang, Zhibao; Du, Bo; Xiong, Qingqing

2014-01-01

Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA) particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 μm to 100 μm, and most were 50-80 μm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug - rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment.

Sodium molybdate prevents hypertension and vascular prostanoid imbalance in fructose-overloaded rats.

PubMed

Peredo, H A; Andrade, V; Donoso, A S; Lee, H J; Puyó, A M

2013-10-01

(1) Fructose (F) overload produces elevated blood pressure (BP), hyperglycaemia, hypertriglyceridemia and insulin resistance, resembling human metabolic syndrome. Previously, we found altered vascular prostanoid (PR) production in this model. (2) Sodium molybdate (Mo), as well as sodium tungstate, causes insulin-like effects and normalizes plasma glucose levels in streptozotocin-treated diabetic rats. We studied the effects of Mo on BP, metabolic parameters and release of PR from the mesenteric vascular bed (MVB) in F-overloaded rats. (3) Four groups of male Sprague-Dawley rats were analysed: Control, tap water to drink; F, F solution 10% W/V to drink; CMo, Mo 100 mg kg day(-1) and FMo, both treatments. After 9 weeks, the animals were killed and MVBs removed and the released PRs measured. (4) F increased BP, glycemia, triglyceridemia and insulinemia. Mo treatment prevented the increases in BP and glycemia, but did not modify triglyceridemia or insulinemia. In addition, Mo decreased BP in controls. (5) Prostaglandins (PG) F2 alpha and E2, PG 6-ketoF1 alpha and thromboxane (TX) B2 , as well as inactive metabolites of prostacyclin (PGI2 ) and TXA2 were detected. F decreased the production of vasodilator PRs PGI2 and PGE2 in MVB. Mo prevented these alterations and increased PGE2 in controls. Vasoconstrict or PRs PGF2 alpha and TXA2 release was not modified. (6) Mo treatment, beyond its known lowering effect on glycemia, prevents the reduction in the vascular release of vasodilator PR observed in this model. This could be one of the mechanisms by which Mo avoids the increase in BP caused by F overload in the rat. © 2013 John Wiley & Sons Ltd.

Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

PubMed Central

Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2011-01-01

Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

Optimal control of malaria: combining vector interventions and drug therapies.

PubMed

Khamis, Doran; El Mouden, Claire; Kura, Klodeta; Bonsall, Michael B

2018-04-24

The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.

Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries.

PubMed

Minoves, Nuria; Balfagón, Gloria; Ferrer, Mercedes

2002-09-01

This study examines the effects of female sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as the modulation of this response by neuronal NO. For this purpose, segments of denuded superior mesenteric artery from ovariectomized (OvX) female Sprague-Dawley rats and from control rats (in oestrus phase) were used. EFS induced frequency-dependent contractions, which were greater in segments from OvX rats than in those from control rats. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester strengthened EFS-elicited contractions to a greater extent in arteries from OvX rats than in those from control rats. Similar results were observed with the preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial neurotoxin capsaicin did not modify EFS-induced contractions in segments from either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP) induced concentration-dependent relaxation, which was greater in segments from control rats than in those from OvX rats. 8-Bromo-cGMP induced similar concentration-dependent relaxation in noradrenaline-precontracted segments from both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD) inhibitor, reduced the relaxation induced by SNP in segments from both groups of rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP in segments from OvX rats, but did not modify it in segments from control rats. EFS induced NO(-)(2) formation, which was greater in segments from OvX than in those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve impulse propagation, abolished release in both cases. These results suggest that EFS induces greater neuronal NO release in mesenteric segments from OvX rats than in those from control rats and, although NO metabolism is also higher, the contribution of net neuronal NO in the vasomotor response to EFS is greater in segments from OvX rats than in those from control rats.

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing.

PubMed

Okwuosa, Tochukwu C; Soares, Cindy; Gollwitzer, Verena; Habashy, Rober; Timmins, Peter; Alhnan, Mohamed A

2018-06-15

A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R 2  = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs. Copyright © 2018 Elsevier B.V. All rights reserved.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

PubMed

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

PubMed

Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

2017-06-01

The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product <10,000 mg/L × IU/L developed hepatotoxicity (sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L × IU/L. When calculated within eight hours of ingestion, mild elevations of the multiplication product fell quickly on repeat testing in patients without ALI or hepatotoxicity. In modified-release paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

PubMed

Liao, Zi-Xian; Liu, Meng-Chia; Kempson, Ivan M; Fa, Yu-Chen; Huang, Kuo-Yen

2017-01-01

Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels, with incorporation of gold nanoparticles (NP). The incorporation of gold NP into MC hydrogels led to a tunable light irradiation response that dictated the hydrogel release rate of leptin. This manuscript demonstrates feasibility in designing tunable thermosensitive hydrogels for loading multimodality therapeutic agents to enhance the bioactivity of leptin for obesity therapy.

A physics-based model for the ionization of samarium by the MOSC chemical releases in the upper atmosphere

NASA Astrophysics Data System (ADS)

Bernhardt, Paul A.; Siefring, Carl L.; Briczinski, Stanley J.; Viggiano, Albert; Caton, Ronald G.; Pedersen, Todd R.; Holmes, Jeffrey M.; Ard, Shaun; Shuman, Nicholas; Groves, Keith M.

2017-05-01

Atomic samarium has been injected into the neutral atmosphere for production of electron clouds that modify the ionosphere. These electron clouds may be used as high-frequency radio wave reflectors or for control of the electrodynamics of the F region. A self-consistent model for the photochemical reactions of Samarium vapor cloud released into the upper atmosphere has been developed and compared with the Metal Oxide Space Cloud (MOSC) experimental observations. The release initially produces a dense plasma cloud that that is rapidly reduced by dissociative recombination and diffusive expansion. The spectral emissions from the release cover the ultraviolet to the near infrared band with contributions from solar fluorescence of the atomic, molecular, and ionized components of the artificial density cloud. Barium releases in sunlight are more efficient than Samarium releases in sunlight for production of dense ionization clouds. Samarium may be of interest for nighttime releases but the artificial electron cloud is limited by recombination with the samarium oxide ion.

Preparation and characterization of temperature-responsive magnetic composite particles for multi-modal cancer therapy.

PubMed

Yao, Aihua; Chen, Qi; Ai, Fanrong; Wang, Deping; Huang, Wenhai

2011-10-01

The temperature-responsive magnetic composite particles were synthesized by emulsion-free polymerization of N-isopropylacrylamide (NIPAAm) and acrylamide (Am) in the presence of oleic acid-modified Fe(3)O(4) nanoparticles. The magnetic properties and heat generation ability of the composite particles were characterized. Furthermore, temperature and alternating magnetic field (AMF) triggered drug release behaviors of vitamin B(12)-loaded composite particles were also examined. It was found that composite particles enabled drug release to be controlled through temperature changes in the neighborhood of lower critical solution temperature. Continuous application of AMF resulted in an accelerated release of the loaded drug. On the other hand, intermittent AMF application to the composite particles resulted in an "on-off", stepwise release pattern. Longer release duration and larger overall release could be achieved by intermittent application of AMF as compared to continuous magnetic field. Such composite particles may be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Method and apparatus for electromagnetically braking a motor

NASA Technical Reports Server (NTRS)

Davis, Donald R. (Inventor); Radford, Nicolaus A (Inventor); Permenter, Frank Noble (Inventor); Parsons, Adam H (Inventor); Mehling, Joshua S (Inventor)

2011-01-01

An electromagnetic braking system and method is provided for selectively braking a motor using an electromagnetic brake having an electromagnet, a permanent magnet, a rotor assembly, and a brake pad. The brake assembly applies when the electromagnet is de-energized and releases when the electromagnet is energized. When applied the permanent magnet moves the brake pad into frictional engagement with a housing, and when released the electromagnet cancels the flux of the permanent magnet to allow a leaf spring to move the brake pad away from the housing. A controller has a DC/DC converter for converting a main bus voltage to a lower braking voltage based on certain parameters. The converter utilizes pulse-width modulation (PWM) to regulate the braking voltage. A calibrated gap is defined between the brake pad and permanent magnet when the brake assembly is released, and may be dynamically modified via the controller.

Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles.

PubMed

Thomas, Courtney R; Ferris, Daniel P; Lee, Jae-Hyun; Choi, Eunjoo; Cho, Mi Hyeon; Kim, Eun Sook; Stoddart, J Fraser; Shin, Jeon-Soo; Cheon, Jinwoo; Zink, Jeffrey I

2010-08-11

Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated the ability to contain and release cargos with mediation by gatekeepers. Magnetic nanocrystals have the ability to exhibit hyperthermic effects when placed in an oscillating magnetic field. In a system combining these two materials and a thermally sensitive gatekeeper, a unique drug delivery system can be produced. A novel material that incorporates zinc-doped iron oxide nanocrystals within a mesoporous silica framework that has been surface-modified with pseudorotaxanes is described. Upon application of an AC magnetic field, the nanocrystals generate local internal heating, causing the molecular machines to disassemble and allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231) were treated with doxorubicin-loaded particles and exposed to an AC field, cell death occurred. This material promises to be a noninvasive, externally controlled drug delivery system with cancer-killing properties.

78 FR 22850 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... million * As defined in Section 47(6) of the Arms Export Control Act. (iii) Description and Quantity or... software continues to be modified via a pre-planned product improvement (P3I) program in order to improve its counter- countermeasure capabilities. No software source code or algorithms will be released. The...

Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.

PubMed

Fass, Ronnie; Inadomi, John; Han, Cong; Mody, Reema; O'Neil, Janet; Perez, M Claudia

2012-03-01

Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Influence of drug loading and type of ointment base on the in vitro performance of acyclovir ophthalmic ointment.

PubMed

Al-Ghabeish, Manar; Xu, Xiaoming; Krishnaiah, Yellela S R; Rahman, Ziyaur; Yang, Yang; Khan, Mansoor A

2015-11-30

The availability of in vitro performance tests such as in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) are critical to comprehensively assure consistent delivery of the active component(s) from semisolid ophthalmic drug products. The objective was to study the impact of drug loading and type of ointment base on the in vitro performance (IVRT and IVPT) of ophthalmic ointments using acyclovir as a model drug candidate. The in vitro drug release for the ointments was evaluated using a modified USP apparatus 2 with Enhancer cells. The transcorneal permeation was carried out using rabbit cornea on modified vertical Franz cells. The drug retention in cornea (DRC) was also determined at the end of transcorneal drug permeation study. The in vitro drug release, transcorneal drug permeation as well as DRC exhibited a proportional increase with increasing drug loading in the ointment. On comparing the in vitro drug release profile with transcorneal permeation profile, it appears that drug release from the ointment is controlling acyclovir transport through the cornea. Furthermore, enhanced in vitro transcorneal permeation relative to the in vitro drug release underscores the importance of the interplay between the physiology of the ocular tissue and ointment formulation. The results indicated that IVRT and IVPT could be used to discriminate the impact of changes in drug load and formulation composition of ophthalmic ointments. Copyright © 2015. Published by Elsevier B.V.

3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release.

PubMed

Kyobula, Mary; Adedeji, Aremu; Alexander, Morgan R; Saleh, Ehab; Wildman, Ricky; Ashcroft, Ian; Gellert, Paul R; Roberts, Clive J

2017-09-10

A hot melt 3D inkjet printing method with the potential to manufacture formulations in complex and adaptable geometries for the controlled loading and release of medicines is presented. This first use of a precisely controlled solvent free inkjet printing to produce drug loaded solid dosage forms is demonstrated using a naturally derived FDA approved material (beeswax) as the drug carrier and fenofibrate as the drug. Tablets with bespoke geometries (honeycomb architecture) were fabricated. The honeycomb architecture was modified by control of the honeycomb cell size, and hence surface area to enable control of drug release profiles without the need to alter the formulation. Analysis of the formed tablets showed the drug to be evenly distributed within the beeswax at the bulk scale with evidence of some localization at the micron scale. An analytical model utilizing a Fickian description of diffusion was developed to allow the prediction of drug release. A comparison of experimental and predicted drug release data revealed that in addition to surface area, other factors such as the cell diameter in the case of the honeycomb geometry and material wettability must be considered in practical dosage form design. This information when combined with the range of achievable geometries could allow the bespoke production of optimized personalised medicines for a variety of delivery vehicles in addition to tablets, such as medical devices for example. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

PubMed

Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

2016-06-01

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. © 2016 John Wiley & Sons A/S.

Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

PubMed

Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

2015-09-30

The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

Chlorhexidine Uptake and Release From Modified Titanium Surfaces and Its Antimicrobial Activity.

PubMed

Ryu, Hyo-Sook; Kim, Yoon-Il; Lim, Bum-Soon; Lim, Young-Jun; Ahn, Sug-Joon

2015-11-01

Decontamination by adjunctive antiseptic agents such as chlorhexidine (CHX) is often recommended for the treatment of peri-implant infections. However, its action on the titanium implant surface needs further research. This study is designed to evaluate the ability of modified titanium surfaces to release chlorhexidine after periodic CHX exposure. Four titanium surfaces were prepared: 1) no surface treatment control (machined surface [MA]); 2) an acid mix of 10% HNO3 and 5% HF (HNF); 3) resorbable blast media (RBM); and 4) sandblasting and acid etching (SLA). Each surface was analyzed using a confocal laser scanning microscope and a scanning electron microscope. Each sample was incubated with whole saliva or phosphate-buffered saline for 2 hours. Measurements of CHX release were performed using spectrometry on days 1, 2, and 5 after 1-minute exposure to 0.5% chlorhexidine digluconate solution during a 5-day cycle. CHX-releasing experiments were repeated three consecutive times for 15 days. The antimicrobial activity of CHX-adsorbed disks was determined by a disk diffusion test using Streptococcus gordonii. The CHX-adsorbed titanium surfaces exhibited a short-term release of CHX, and CHX levels dropped rapidly within 3 days. SLA and RBM with smaller and narrower depressions released more CHX than HNF and MA, specifically in the saliva-coated group. The disk diffusion test revealed that after CHX uptake, saliva-coated SLA and RBM showed the highest antimicrobial activity. This study suggests that CHX release is significantly influenced by titanium surface modifications and that SLA and RBM might provide effective CHX uptake capacity in the saliva-filled oral cavity.

Surface-Modified P(HEMA-co-MAA) Nanogel Carriers for Oral Vaccine Delivery: Design, Characterization, and In Vitro Targeting Evaluation

PubMed Central

Durán-Lobato, Matilde; Carrillo-Conde, Brenda; Khairandish, Yasmine; Peppas, Nicholas A.

2015-01-01

Oral drug delivery is a route of choice for vaccine administration because of its noninvasive nature and thus efforts have focused on efficient delivery of vaccine antigens to mucosal sites. An effective oral vaccine delivery system must protect the antigen from degradation upon mucosal delivery, penetrate mucosal barriers, and control the release of the antigen and costimulatory and immunomodulatory agents to specific immune cells (i.e., APCs). In this paper, mannan-modified pH-responsive P(HEMA-co-MAA) nanogels were synthesized and assessed as carriers for oral vaccination. The nanogels showed pH-sensitive properties, entrapping and protecting the loaded cargo at low pH values, and triggered protein release after switching to intestinal pH values. Surface decoration with mannan as carbohydrate moieties resulted in enhanced internalization by macrophages as well as increasing the expression of relevant costimulatory molecules. These findings indicate that mannan-modified P(HEMA-co-MAA) nanogels are a promising approach to a more efficacious oral vaccination regimen. PMID:24955658

NGR-modified pH-sensitive liposomes for controlled release and tumor target delivery of docetaxel.

PubMed

Gu, Zili; Chang, Minglu; Fan, Yang; Shi, Yanbin; Lin, Guimei

2017-12-01

As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of controlled drug release systems based on thiolated polymers.

PubMed

Bernkop-Schnürch, A; Scholler, S; Biebel, R G

2000-05-03

The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

Preparation of mesoporous silica microparticles by sol-gel/emulsion route for protein release.

PubMed

Vlasenkova, Mariya I; Dolinina, Ekaterina S; Parfenyuk, Elena V

2018-04-06

Encapsulation of therapeutic proteins into particles from appropriate material can improve both stability and delivery of the drugs, and the obtained particles can serve as a platform for development of their new oral formulations. The main goal of this work was development of sol-gel/emulsion method for preparation of silica microcapsules capable of controlled release of encapsulated protein without loss of its native structure. For this purpose, the reported in literature direct sol-gel/W/O/W emulsion method of protein encapsulation was used with some modifications, because the original method did not allow to prepare silica microcapsules capable for protein release. The particles were synthesized using sodium silicate and tetraethoxysilane as silica precursors and different compositions of oil phase. In vitro kinetics of bovine serum albumin (BSA) release in buffer (pH 7.4) was studied by Fourier transform infrared (FTIR) and fluorescence spectrometry, respectively. Structural state of encapsulated BSA and after release was evaluated. It was found that the synthesis conditions influenced substantially the porous structure of the unloaded silica particles, release properties of the BSA-loaded silica particles and structural state of the encapsulated and released protein. The modified synthesis conditions made it possible to obtain the silica particles capable of controlled release of the protein during a week without loss of the protein native structure.

Experience with Ada on the F-18 High Alpha Research Vehicle Flight Test Program

NASA Technical Reports Server (NTRS)

Regenie, Victoria A.; Earls, Michael; Le, Jeanette; Thomson, Michael

1992-01-01

Considerable experience was acquired with Ada at the NASA Dryden Flight Research Facility during the on-going High Alpha Technology Program. In this program, an F-18 aircraft was highly modified by the addition of thrust-vectoring vanes to the airframe. In addition, substantial alteration was made in the original quadruplex flight control system. The result is the High Alpha Research Vehicle. An additional research flight control computer was incorporated in each of the four channels. Software for the research flight control computer was written in Ada. To date, six releases of this software have been flown. This paper provides a detailed description of the modifications to the research flight control system. Efficient ground-testing of the software was accomplished by using simulations that used the Ada for portions of their software. These simulations are also described. Modifying and transferring the Ada for flight software to the software simulation configuration has allowed evaluation of this language. This paper also discusses such significant issues in using Ada as portability, modifiability, and testability as well as documentation requirements.

Experience with Ada on the F-18 High Alpha Research Vehicle flight test program

NASA Technical Reports Server (NTRS)

Regenie, Victoria A.; Earls, Michael; Le, Jeanette; Thomson, Michael

1994-01-01

Considerable experience has been acquired with Ada at the NASA Dryden Flight Research Facility during the on-going High Alpha Technology Program. In this program, an F-18 aircraft has been highly modified by the addition of thrust-vectoring vanes to the airframe. In addition, substantial alteration was made in the original quadruplex flight control system. The result is the High Alpha Research Vehicle. An additional research flight control computer was incorporated in each of the four channels. Software for the research flight control computer was written Ada. To date, six releases of this software have been flown. This paper provides a detailed description of the modifications to the research flight control system. Efficient ground-testing of the software was accomplished by using simulations that used the Ada for portions of their software. These simulations are also described. Modifying and transferring the Ada flight software to the software simulation configuration has allowed evaluation of this language. This paper also discusses such significant issues in using Ada as portability, modifiability, and testability as well as documentation requirements.

Retardation of Antigen Release from DNA Hydrogel Using Cholesterol-Modified DNA for Increased Antigen-Specific Immune Response.

PubMed

Umeki, Yuka; Saito, Masaaki; Takahashi, Yuki; Takakura, Yoshinobu; Nishikawa, Makiya

2017-10-01

Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction-based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol-modified DNA and urea-denatured OVA (udOVA). Cholesterol-modified DNA forms a hydrogel, Dgel(chol), and induces IL-6 mRNA expression in mouse skin after intradermal injection, as DNA without cholesterol does. Cholesterol-modified DNA associated with OVA and denaturation of OVA using urea increases the interaction. The release of udOVA from Dgel(chol) is significantly slower than that from DNA hydrogel with no cholesterol, Dgel. Moreover, intratumoral injections of udOVA/Dgel(chol) significantly inhibit the growth of EG7-OVA tumors in mice. These results indicate that sustained release of antigen from Dgel can be achieved by the combination of urea denaturation and cholesterol modification, and retardation of antigen release is effective to induce antigen-specific cancer immunity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

PubMed

Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

2016-11-01

This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

NASA Astrophysics Data System (ADS)

Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

2017-09-01

Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine

PubMed Central

Chen, Yufei; Traore, Yannick Leandre; Li, Amanda; Fowke, Keith R; Ho, Emmanuel A

2014-01-01

Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections. PMID:25336923

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

PubMed

Davidson, Iain G; Langner, Eric J; Plowman, Steven V; Blair, Julian A

2003-03-26

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium. Copyright 2003 Elsevier Science B.V.

Can lipid nanoparticles improve intestinal absorption?

PubMed

Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

2016-12-30

Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery

PubMed Central

Hu, Yan; Ke, Lei; Chen, Hao; Zhuo, Ma; Yang, Xinzhou; Zhao, Dan; Zeng, Suying; Xiao, Xincai

2017-01-01

To avoid the side effects caused by nonspecific targeting, premature release, weak selectivity, and poor therapeutic efficacy of current nanoparticle-based systems used for drug delivery, we fabricated natural material-decorated nanoparticles as a multifunctional, membrane-controlled targeted drug delivery system. The nanocomposite material coated with a membrane was biocompatible and integrated both specific tumor targeting and responsiveness to stimulation, which improved transmission efficacy and controlled drug release. Mesoporous silica nanoparticles (MSNs), which are known for their biocompatibility and high drug-loading capacity, were selected as a model drug container and carrier. The membrane was established by the polyelectrolyte composite method from chitosan (CS) which was sensitive to the acidic tumor microenvironment, folic acid-modified CS which recognizes the folate receptor expressed on the tumor cell surface, and a CD44 receptor-targeted polysaccharide hyaluronic acid. We characterized the structure of the nanocomposite as well as the drug release behavior under the control of the pH-sensitive membrane switch and evaluated the antitumor efficacy of the system in vitro. Our results provide a basis for the design and fabrication of novel membrane-controlled nanoparticles with improved tumor-targeting therapy. PMID:29200852

Injectable nanocomposite cryogels for versatile protein drug delivery.

PubMed

Koshy, Sandeep T; Zhang, David K Y; Grolman, Joshua M; Stafford, Alexander G; Mooney, David J

2018-01-01

Sustained, localized protein delivery can enhance the safety and activity of protein drugs in diverse disease settings. While hydrogel systems are widely studied as vehicles for protein delivery, they often suffer from rapid release of encapsulated cargo, leading to a narrow duration of therapy, and protein cargo can be denatured by incompatibility with the hydrogel crosslinking chemistry. In this work, we describe injectable nanocomposite hydrogels that are capable of sustained, bioactive, release of a variety of encapsulated proteins. Injectable and porous cryogels were formed by bio-orthogonal crosslinking of alginate using tetrazine-norbornene coupling. To provide sustained release from these hydrogels, protein cargo was pre-adsorbed to charged Laponite nanoparticles that were incorporated within the walls of the cryogels. The presence of Laponite particles substantially hindered the release of a number of proteins that otherwise showed burst release from these hydrogels. By modifying the Laponite content within the hydrogels, the kinetics of protein release could be precisely tuned. This versatile strategy to control protein release simplifies the design of hydrogel drug delivery systems. Here we present an injectable nanocomposite hydrogel for simple and versatile controlled release of therapeutic proteins. Protein release from hydrogels often requires first entrapping the protein in particles and embedding these particles within the hydrogel to allow controlled protein release. This pre-encapsulation process can be cumbersome, can damage the protein's activity, and must be optimized for each protein of interest. The strategy presented in this work simply premixes the protein with charged nanoparticles that bind strongly with the protein. These protein-laden particles are then placed within a hydrogel and slowly release the protein into the surrounding environment. Using this method, tunable release from an injectable hydrogel can be achieved for a variety of proteins. This strategy greatly simplifies the design of hydrogel systems for therapeutic protein release applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

PubMed

Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

2012-12-01

The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p < 0.05) with the modified-release form [tmax: 3.15 (1.28) vs. 0.85 (0.32) h and tmax-ss: 2.92 (1.19) vs. 1.04 (0.43) h]. There was no difference noted in the average plasma concentrations [Cavgτ: 23.90 (7.90) vs. 20.64 (7.43) ng/mL after the first dose; and Cavg-ss: 31.14 (9.64) vs. 35.59 (12.29) ng/mL after the last dose, (p > 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

PubMed

Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim

2015-10-01

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

Hyaluronic Acid-Based pH-Sensitive Polymer-Modified Liposomes for Cell-Specific Intracellular Drug Delivery Systems.

PubMed

Miyazaki, Maiko; Yuba, Eiji; Hayashi, Hiroshi; Harada, Atsushi; Kono, Kenji

2018-01-17

For the enhancement of therapeutic effects and reduction of side effects derived from anticancer drugs in cancer chemotherapy, it is imperative to develop drug delivery systems with cancer-specificity and controlled release function inside cancer cells. pH-sensitive liposomes are useful as an intracellular drug delivery system because of their abilities to transfer their contents into the cell interior through fusion or destabilization of endosome, which has weakly acidic environment. We earlier reported liposomes modified with various types of pH-sensitive polymers based on synthetic polymers and biopolymers as vehicles for intracellular drug delivery systems. In this study, hyaluronic acid (HA)-based pH-sensitive polymers were designed as multifunctional polymers having not only pH-sensitivity but also targeting properties to cells expressing CD44, which is known as a cancer cell surface marker. Carboxyl group-introduced HA derivatives of two types, MGlu-HA and CHex-HA, which have a more hydrophobic side chain structure than that of MGlu-HA, were synthesized by reaction with various dicarboxylic anhydrides. These polymer-modified liposomes were stable at neutral pH, but showed content release under weakly acidic conditions. CHex-HA-modified liposomes delivered their contents into CD44-expressing cells more efficiently than HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, whereas the same liposomes were taken up only slightly by cells expressing CD44 proteins less. Competition assay using free HA or other polymers revealed that HA derivative-modified liposomes might be recognized by CD44. Therefore, HA-derivative-modified liposomes are useful as cell-specific intracellular drug delivery systems.

[Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre].

PubMed

Höjer, Jonas; Salmonson, Helene; Sjöberg, Gunilla; Tellerup, Markus; Brogren, Jacob

2016-11-10

Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre  The sales of modified-release paracetamol tablets are steadily increasing in Sweden as are the number of overdose cases with this formulation. The Swedish Poisons Information Centre has noted that the standard treatment protocol with N-acetylcysteine (NAC), which is based on overdoses with immediate-release paracetamol formulations, is often inadequate in this setting. In this paper, an adult who overdosed on 66.5 grams of modified-release paracetamol tablets and developed severe liver impairment (max ALT 6,660 U/l) despite timely and rigorous NAC treatment is presented. The patient's peak S-paracetamol of 2,800 µmol/l was delayed to 19 hours post-ingestion. Moreover, a pharmacokinetic and clinical study of similar cases showed that seven (21%) of the 34 patients who received NAC treatment within 8 hours after ingestion developed liver impairment. Finally, new Swedish guidelines for management of these cases are presented. The guidelines are also available on www.giftinfo.se.

Peroxide-modified titanium dioxide: a chemical analog of putative Martian soil oxidants

NASA Technical Reports Server (NTRS)

Quinn, R. C.; Zent, A. P.

1999-01-01

Hydrogen peroxide chemisorbed on titanium dioxide (peroxide-modified titanium dioxide) is investigated as a chemical analog to the putative soil oxidants responsible for the chemical reactivity seen in the Viking biology experiments. When peroxide-modified titanium dioxide (anatase) was exposed to a solution similar to the Viking labeled release (LR) experiment organic medium, CO2 gas was released into the sample cell headspace. Storage of these samples at 10 degrees C for 48 hr prior to exposure to organics resulted in a positive response while storage for 7 days did not. In the Viking LR experiment, storage of the Martian surface samples for 2 sols (approximately 49 hr) resulted in a positive response while storage for 141 sols essentially eliminated the initial rapid release of CO2. Heating the peroxide-modified titanium dioxide to 50 degrees C prior to exposure to organics resulted in a negative response. This is similar to, but not identical to, the Viking samples where heating to approximately 46 degrees C diminished the response by 54-80% and heating to 51.5 apparently eliminated the response. When exposed to water vapor, the peroxide-modified titanium dioxide samples release O2 in a manner similar to the release seen in the Viking gas exchange experiment (GEx). Reactivity is retained upon heating at 50 degrees C for three hours, distinguishing this active agent from the one responsible for the release of CO2 from aqueous organics. The release of CO2 by the peroxide-modified titanium dioxide is attributed to the decomposition of organics by outer-sphere peroxide complexes associated with surface hydroxyl groups, while the release of O2 upon humidification is attributed to more stable inner-sphere peroxide complexes associated with Ti4+ cations. Heating the peroxide-modified titanium dioxide to 145 degrees C inhibited the release of O2, while in the Viking experiments heating to this temperature diminished but did not eliminated the response. Although the thermal stability of the titanium-peroxide complexes in this work is lower than the stability seen in the Viking experiments, it is expected that similar types of complexes will form in titanium containing minerals other than anatase and the stability of these complexes will vary with surface hydroxylation and mineralogy.

Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

PubMed Central

Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

2015-01-01

The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

Performance Validation of Version 152.0 ANSER Control Laws for the F-18 HARV

NASA Technical Reports Server (NTRS)

Messina, Michael D.

1996-01-01

The Actuated Nose Strakes for Enhanced Rolling (ANSER) Control Laws were modified as a result of Phase 3 F/A-18 High Alpha Research Vehicle (HARV) flight testing. The control law modifications for the next software release were designated version 152.0. The Ada implementation was tested in the Hardware-In-the-Loop (HIL) simulation and results were compared to those obtained with the NASA Langley batch Fortran implementation of the control laws which are considered the 'truth model.' This report documents the performance validation test results between these implementations for ANSER control law version 152.0.

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

PubMed

Lai, Yen-Ho; Chiang, Chih-Sheng; Kao, Tzu-Hsun; Chen, San-Yuan

2018-01-01

Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy. In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added. With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment. The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.

Fluoride releasing and enamel demineralization around orthodontic brackets by fluoride-releasing composite containing nanoparticles.

PubMed

Melo, Mary A S; Morais, Weslanny A; Passos, Vanara F; Lima, Juliana P M; Rodrigues, Lidiany K A

2014-05-01

Fluoride-containing materials have been suggested to control enamel demineralization around orthodontic brackets during the treatment with fixed appliances. The improvement of their properties has been made through innovations, such as the application of nanotechnology by incorporation of nanofillers. This in vitro study evaluated the capacity of fluoride releasing and enamel demineralization inhibition of fluoride-releasing nanofilled cement around orthodontic brackets using an artificial caries biofilm model. Forty bovine enamel discs were selected by evaluating surface microhardness and randomized into four groups (n = 10): non-fluoride-releasing microfilled composite, fluoride-releasing microfilled composite, resin-modified glass ionomer cement (RMGI), and fluoride-releasing nanofilled composite (FN). After brackets bonding in each disc, the specimens were subjected to a cariogenic challenge through a Streptococcus mutans biofilm model. After the experimental period, the biofilm formed around the brackets was collected for fluoride analysis and the mineral loss around the brackets was determined by integrated demineralization via cross-sectional microhardness measurement at 20 and 70 μm from the bracket margin. Additionally, samples of each group were subjected to energy-dispersive X-ray spectroscopy (EDX) analysis examined under a scanning electron microscopy (SEM). ANOVA followed by Tukey test were applied for fluoride concentration and mineral loss data, respectively. At both distances, only RMGI statistically differed from the other groups presenting the lowest demineralization, although there was a trend to a lower demineralization of enamel around brackets in FN group. Similar condition was found to fluoride concentration and EDX/SEM analysis. Under the cariogenic exposure condition of this study, the fluoride-releasing nanofilled material had similar performance to fluoride-releasing microfilled materials. The presence of nanofillers in the fluoride-releasing materials studied did not promote further benefits against caries lesion development around brackets and presented inferior demineralization inhibition than the resin-modified glass ionomer material.

Effects of peptides derived from dietary proteins on mucus secretion in rat jejunum.

PubMed

Claustre, Jean; Toumi, Férial; Trompette, Aurélien; Jourdan, Gérard; Guignard, Henri; Chayvialle, Jean Alain; Plaisancié, Pascale

2002-09-01

The hypothesis that dietary proteins or their hydrolysates may regulate intestinal mucin discharge was investigated in the isolated vascularly perfused rat jejunum using an enzyme-linked immunosorbent assay for rat intestinal mucins. On luminal administration, casein hydrolysate [0.05-5% (wt/vol)] stimulated mucin secretion in rat jejunum (maximal response at 417% of controls). Lactalbumin hydrolysate (5%) also evoked mucin discharge. In contrast, casein, and a mixture of amino acids was without effect. Chicken egg albumin and its hydrolysate or meat hydrolysate also did not modify mucin release. Interestingly, casein hydrolysate-induced mucin secretion was abolished by intra-arterial TTX or naloxone (an opioid antagonist). beta-Casomorphin-7, an opioid peptide released from beta-casein on milk ingestion, induced a strong mucin secretion (response at 563% of controls) that was inhibited by naloxone. Intra-arterial beta-casomorphin-7 also markedly increased mucin secretion (410% of controls). In conclusion, two enzymatic milk protein hydrolysates (casein and lactalbumin hydrolysates) and beta-casomorphin-7, specifically, induced mucin release in rat jejunum. The casein hydrolysate-induced mucin secretion is triggered by a neural pathway and mediated by opioid receptor activation.

Self-assembling N-(9-Fluorenylmethoxycarbonyl)-l-Phenylalanine hydrogel as novel drug carrier.

PubMed

Snigdha, Kirti; Singh, Brijesh K; Mehta, Abijeet Singh; Tewari, R P; Dutta, P K

2016-12-01

Supramolecular hydrogel as a novel drug carrier was prepared from N-(9-Fluorenylmethoxycarbonyl) (Fmoc) modified l-phenylalanine. Its different properties like stability at different pH, temperature and rheology were evaluated in reference to salicylic acid (SA) as a model drug, entrapped in the supramolecular hydrogel network. The release behaviour of SA drug in supramolecular hydrogel was investigated by UV-vis spectroscopy. The influence of hydrogelator, pH values of the accepting media, temperature and concentration of SA drug on the release behaviour was investigated under static conditions. The results indicated that the release rate of SA in the supramolecular hydrogels was slightly retarded with an increase of the hydrogelator concentration. Also, the release rates of SA increased with an increase of temperature and its concentration. Furthermore, the release behaviour of SA was found to be different at various pH values in buffers. The study of the release kinetics indicated that the release behaviour of SA from the carrier was in accord with the Peppas model and the diffusion controlled mechanism involved in the Fickian model. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of Industrial Polyurethane Foams Modified with Antimicrobial Copper Nanoparticles

PubMed Central

Sportelli, Maria Chiara; Picca, Rosaria Anna; Ronco, Roberto; Bonerba, Elisabetta; Tantillo, Giuseppina; Pollini, Mauro; Sannino, Alessandro; Valentini, Antonio; Cataldi, Tommaso R.I.; Cioffi, Nicola

2016-01-01

Antimicrobial copper nanoparticles (CuNPs) were electrosynthetized and applied to the controlled impregnation of industrial polyurethane foams used as padding in the textile production or as filters for air conditioning systems. CuNP-modified materials were investigated and characterized morphologically and spectroscopically, by means of Transmission Electron Microscopy (TEM), and X-ray Photoelectron Spectroscopy (XPS). The release of copper ions in solution was studied by Electro-Thermal Atomic Absorption Spectroscopy (ETAAS). Finally, the antimicrobial activity of freshly prepared, as well as aged samples—stored for two months—was demonstrated towards different target microorganisms. PMID:28773665

pH-Sensitive O6-Benzylguanosine Polymer Modified Magnetic Nanoparticles for Treatment of Glioblastomas.

PubMed

Stephen, Zachary R; Gebhart, Rachel N; Jeon, Mike; Blair, Allison A; Ellenbogen, Richard G; Silber, John R; Zhang, Miqin

2017-01-18

Nanoparticle-mediated delivery of chemotherapeutics has demonstrated potential in improving anticancer efficacy by increasing serum half-life and providing tissue specificity and controlled drug release to improve biodistribution of hydrophobic chemotherapeutics. However, suboptimal drug loading, particularly for solid core nanoparticles (NPs), remains a challenge that limits their clinical application. In this study we formulated a NP coated with a pH-sensitive polymer of O 6 -methylguanine-DNA methyltransferase (MGMT) inhibitor analog, dialdehyde modified O 6 -benzylguanosine (DABGS) to achieve high drug loading, and polyethylene glycol (PEG) to ameliorate water solubility and maintain NP stability. The base nanovector consists of an iron oxide core (9 nm) coated with hydrazide functionalized PEG (IOPH). DABGS and PEG-dihydrazide were polymerized on the iron oxide nanoparticle surface (IOPH-pBGS) through acid-labile hydrazone bonds utilizing a rapid, freeze-thaw catalysis approach. DABGS polymerization was confirmed by FTIR and quantitated by UV-vis spectroscopy. IOPH-pBGS demonstrated excellent drug loading of 33.4 ± 5.1% by weight while maintaining small size (36.5 ± 1.8 nm). Drug release was monitored at biologically relevant pHs and demonstrated pH dependent release with maximum release at pH 5.5 (intracellular conditions), and minimal release at physiological pH (7.4). IOPH-pBGS significantly suppressed activity of MGMT and potentiated Temozolomide (TMZ) toxicity in vitro, demonstrating potential as a new treatment option for glioblastomas (GBMs).

Safe and efficient pH sensitive tumor targeting modified liposomes with minimal cytotoxicity.

PubMed

Wang, Lilin; Geng, Di; Su, Haijia

2014-11-01

Incorporating the pH-sensitivity of octylamine grafted poly aspartic acid (PASP) with the biocompatibility of liposomes, a novel pH sensitive drug delivery system, octylamine-graft-PASP (PASP-g-C8) modified liposomes (OPLPs), was obtained. Since hydrophobic chains have been grafted into PASP backbones, the octylamine chain could act as the "anchor" to implant onto liposomes. The structure of PASP-g-C8, involving long-chain and hydrophobic anchors can significantly enhance the stability of the drug carrier. The shortcoming of single PASP chain modified liposomes (PLPs), that cannot sustain a slow and controlled release especially in a physiological pH solution (resembling normal tissues of pH 7.4) is thus overcome. Drug release experiments were carried out and the result showed that OPLPs sustained a slow and steady release in comparison with PLPs in the physiological pH 7.4 environment. However, OPLPs can provide a fast release in subacid environment (pH 5.0 of resembled tumor tissues). The results of diameter analysis and zeta potential demonstrated that OPLPs presented a larger diameter and higher electronegativity. Furthermore, in the "chain-anchor" structure of PASP-g-C8, the degree of substitution (DS) of the "anchor" is a remarkable factor to alter the pH-sensitivity of OPLPs. The in vitro tumor inhibition and cell toxicity studies revealed that tumor cells treated with OPLPs survived only 35.0% after 48 h whereas normal cells survived 100% in the same condition. The pH sensitive OPLPs are promising tumor targeting drug delivery with high tumor inhibition and insignificant cytotoxicity. Copyright © 2014. Published by Elsevier B.V.

RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer.

PubMed

Feng, Chan; Li, Xiaoyan; Dong, Chunyan; Zhang, Xuemei; Zhang, Xie; Gao, Yong

2015-01-01

In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM) liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0-∞ (1.54-fold), mean residence time (2.09-fold), and elimination half-life (1.2-fold) when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.

RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

PubMed Central

Feng, Chan; Li, Xiaoyan; Dong, Chunyan; Zhang, Xuemei; Zhang, Xie; Gao, Yong

2015-01-01

In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM) liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was −22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0–∞ (1.54-fold), mean residence time (2.09-fold), and elimination half-life (1.2-fold) when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts. PMID:26316700

The physicochemical properties of a spray dried glutinous rice starch biopolymer.

PubMed

Laovachirasuwan, Pornpun; Peerapattana, Jomjai; Srijesdaruk, Voranuch; Chitropas, Padungkwan; Otsuka, Makoto

2010-06-15

Glutinous rice starch (GRS) is a biopolymer used widely in the food industry but not at all in the pharmaceutical industry. There are several ways to modify this biopolymer. Physical modification is simple and cheap because it requires no chemicals or biological agents. The aim of this study was to characterize the physicochemical properties of a spray dried glutinous rice starch (SGRS) produced from pregelatinized GRS. The surface morphology changed from an irregular to concave spherical shape as revealed by Scanning Electron Microscopy (SEM). SGRS was almost amorphous as determined by X-ray Diffraction (XRD) spectroscopy. The water molecules became linked through hydrogen bonds to the exposed hydroxyl group of amorphous SGRS as determined by Near Infrared (NIR) spectroscopy. Then, SGRS formed a colloid gel matrix with water and developed a highly viscous gelatinous form as determined using Differential Scanning Calorimetry (DSC) and a stress control type rheometer. In addition, SGRS can swell and produce a gelatinous surface barrier like a hydrophilic matrix biopolymer which controls drug release. Therefore, a novel application of SGRS is as a sustained release modifier for direct compression tablets in the pharmaceutical industry. Copyright 2010 Elsevier B.V. All rights reserved.

Coral reef fish predator maintains olfactory acuity in degraded coral habitats.

PubMed

Natt, Michael; Lönnstedt, Oona M; McCormick, Mark I

2017-01-01

Coral reefs around the world are rapidly degrading due to a range of environmental stressors. Habitat degradation modifies the sensory landscape within which predator-prey interactions occur, with implications for olfactory-mediated behaviours. Predator naïve settlement-stage damselfish rely on conspecific damage-released odours (i.e., alarm odours) to inform risk assessments. Yet, species such as the Ambon damselfish, Pomacentrus amboinensis, become unable to respond appropriately to these cues when living in dead-degraded coral habitats, leading to increased mortality through loss of vigilance. Reef fish predators also rely on odours from damaged prey to locate, assess prey quality and engage in prey-stealing, but it is unknown whether their responses are also modified by the change to dead-degraded coral habitats. Implications for prey clearly depend on how their predatory counterparts are affected, therefore the present study tested whether olfactory-mediated foraging responses in the dusky dottyback, Pseudochromis fuscus, a common predator of P. amboinensis, were similarly affected by coral degradation. A y-maze was used to measure the ability of Ps. fuscus to detect and move towards odours, against different background water sources. Ps. fuscus were exposed to damage-released odours from juvenile P. amboinensis, or a control cue of seawater, against a background of seawater treated with either healthy or dead-degraded hard coral. Predators exhibited an increased time allocation to the chambers of y-mazes injected with damage-released odours, with comparable levels of response in both healthy and dead-degraded coral treated waters. In control treatments, where damage-released odours were replaced with a control seawater cue, fish showed no increased preference for either chamber of the y-maze. Our results suggest that olfactory-mediated foraging behaviours may persist in Ps. fuscus within dead-degraded coral habitats. Ps. fuscus may consequently gain a sensory advantage over P. amboinensis, potentially altering the outcome of predator-prey interactions.

Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers.

PubMed

Reddy, Arun B; Reddy, Narendar D

2017-07-01

Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC K 4 M and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.

Putting gold nanocages to work for optical imaging, controlled release and cancer theranostics

PubMed Central

Pang, Bo; Yang, Xuan; Xia, Younan

2016-01-01

Gold nanocages are hollow nanostructures with ultrathin, porous walls. They are bio-inert and their surface can be readily modified with functional groups to specifically interact with the biological system of interest. They have remarkable optical properties, including localized surface plasmon resonance peaks tunable to the near-infrared region, strong absorption and scattering, as well as two- and three-photon luminescence. With the establishment of robust protocols for both synthesis and surface functionalization, Au nanocages have been extensively explored for various biomedical applications. In this review, we begin with a brief account of the synthesis and properties of Au nanocages, and then highlight some of the recent developments in applying them to an array of biomedical applications related to optical imaging, controlled release and cancer theranostics. PMID:27348546

Gelator-polysaccharide hybrid hydrogel for selective and controllable dye release.

PubMed

Li, Ping; Dou, Xiao-Qiu; Tang, Yi-Tian; Zhu, Shenmin; Gu, Jiajun; Feng, Chuan-Liang; Zhang, Di

2012-12-01

In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular-Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide (sodium alginate). A set of techniques including Fourier transform infrared (FT-IR) spectroscopy, (1)H Nuclear Magnetic Resonance ((1)H NMR), X-ray powder diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had confirmed a β-turn arrangement of PDB gelators and a semi-interpenetrating network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers and polysaccharide chains. The evaluation of physicochemical properties of hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better mechanical and water retention properties than LMWG hydrogels. The release study of dyes (model drug) from both LMWG and hybrid hydrogels was carried out. Compared with PDB based hydrogels, hybrid hydrogels show a selective and controllable release property for certain dyes. The results suggest LMWG-polysaccharide hybrid gels may find potential applications as promising drug delivery vehicles for drug molecules. Copyright © 2012 Elsevier Inc. All rights reserved.

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Light-Responsive and pH-Responsive DNA Microcapsules for Controlled Release of Loads.

PubMed

Huang, Fujian; Liao, Wei-Ching; Sohn, Yang Sung; Nechushtai, Rachel; Lu, Chun-Hua; Willner, Itamar

2016-07-20

A method to assemble light-responsive or pH-responsive microcapsules loaded with different loads (tetramethylrhodamine-modified dextran, TMR-D; microperoxidase-11, MP-11; CdSe/ZnS quantum dots; or doxorubicin-modified dextran, DOX-D) is described. The method is based on the layer-by-layer deposition of sequence-specific nucleic acids on poly(allylamine hydrochloride)-functionalized CaCO3 core microparticles, loaded with the different loads, that after the dissolution of the core particles with EDTA yields the stimuli-responsive microcapsules that include the respective loads. The light-responsive microcapsules are composed of photocleavable o-nitrobenzyl-phosphate-modified DNA shells, and the pH-responsive microcapsules are made of a cytosine-rich layer cross-linked by nucleic acid bridges. Irradiating the o-nitrobenzyl phosphate-functionalized microcapsules, λ = 365 nm, or subjecting the pH-responsive microcapsules to pH = 5.0, results in the cleavage of the microcapsule shells and the release of the loads. Preliminary studies address the cytotoxicity of the DOX-D-loaded microcapsules toward MDA-MB-231 breast cancer cells and normal MCF-10A breast epithelial cells. Selective cytotoxicity of the DOX-D-loaded microcapsules toward cancer cells is demonstrated.

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

PubMed

Gohel, M C; Patel, M M; Amin, A F

2003-05-01

This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

A novel grapheme oxide-modified collagen-chitosan bio-film for controlled growth factor release in wound healing applications.

PubMed

Liu, Ting; Dan, Weihua; Dan, Nianhua; Liu, Xinhua; Liu, Xuexu; Peng, Xu

2017-08-01

Collagen-chitosan composite film modified with grapheme oxide (GO) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), termed CC-G-E film, was loaded with basic fibroblast growth factor (bFGF) as the development of an efficacious wound healing device. In this study we report a novel drug delivery system that prevents the initial burst release and loss of bioactivity of drugs in vitro and in vivo applications. The results showed that CC-G-E film possessed improved thermal stability and a higher rate of crosslinking with increased mechanical properties when the dosage of GO was between 0.03% and 0.07%. It was shown that the in vitro release of bFGF from CC-G-E film continued for more than 28d. Furthermore, the CC-G-E films demonstrated excellent in vitro biocompatibility following culture with L929 fibroblasts in terms of cell adhesion and proliferation. CC-G-E films were implanted into Sprague-Dawley rats to characterize their ability to repair full-thickness skin wounds. Results showed that the CC-G-E film accelerated the wound healing process compared with the blank control. Based on all the results, it was concluded that CC-G-E film operates as a novel drug delivery system and due to its performance in wound remodeling, has potential to be developed as a wound dressing material. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast feeding increases vasoconstriction induced by electrical field stimulation in rat mesenteric artery. Role of neuronal nitric oxide and ATP.

PubMed

Blanco-Rivero, Javier; Sastre, Esther; Caracuel, Laura; Granado, Miriam; Balfagón, Gloria

2013-01-01

The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF) affects the vasomotor response induced by electrical field stimulation (EFS), participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. Experiments were performed in female Sprague-Dawley rats (3 months old), divided into three groups: Control (in oestrous phase), mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase). Vasomotor response to EFS, noradrenaline (NA) and nitric oxide (NO) donor DEA-NO were studied. Neuronal NO synthase (nNOS) and phosphorylated nNOS (P-nNOS) protein expression were analysed and NO, superoxide anion (O(2)(.-)), NA and ATP releases were also determined. EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O(2)(.-) production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats.

Breast Feeding Increases Vasoconstriction Induced by Electrical Field Stimulation in Rat Mesenteric Artery. Role of Neuronal Nitric Oxide and ATP

PubMed Central

Caracuel, Laura; Granado, Miriam; Balfagón, Gloria

2013-01-01

Objectives The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF) affects the vasomotor response induced by electrical field stimulation (EFS), participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. Methods Experiments were performed in female Sprague-Dawley rats (3 months old), divided into three groups: Control (in oestrous phase), mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase). Vasomotor response to EFS, noradrenaline (NA) and nitric oxide (NO) donor DEA-NO were studied. Neuronal NO synthase (nNOS) and phosphorylated nNOS (P-nNOS) protein expression were analysed and NO, superoxide anion (O2 .–), NA and ATP releases were also determined. Results EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O2 .– production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. Conclusion Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats. PMID:23342008

Resin-modified glass ionomer cements: fluoride release and influence on Streptococcus mutans growth.

PubMed

Friedl, K H; Schmalz, G; Hiller, K A; Shams, M

1997-02-01

The aims of the present study were to measure the fluoride release of 1 glass ionomer cement, 1 cermet, 3 resin-modified glass ionomer cements and 1 compomer, and to determine the influence of each material on bacterial growth. Test specimens were eluted in saline for 180 days. Every 2 days, the specimens were transferred into fresh saline and the fluoride content of the solution was measured. Furthermore, 48-h, 14-d, 90-d, and 180-d eluates were inoculated with Streptococcus mutans and bacterial growth was recorded nephelometrically. Fluoride release dropped significantly over time for each material with values between 6.2 (Ketac-Silver) and 29.3 (Photac-Fil) ppm after 48 h to values between 0.6 (Ketac-Silver) and 1.7 (Ketac-Fil, Vitremer) ppm after 180 days. Each material reduced bacterial growth at each time of examination, but the effect decreased significantly over time with a maximum growth of 71.7% (Ketac-Fil) to 85.6% (Ketac-Silver) after 48 h and 94.7 (Vitremer) to 99.0% (Ketac-Silver) after 180 days (growth control = 100%). Both Ketac-Silver and Dyract showed a significantly lower inhibiting effect on bacterial growth than the other materials. The tested materials showed a good correlation between fluoride release and influence on bacterial growth. However, both effects dropped dramatically over the 180-days period.

Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

PubMed Central

Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

2011-01-01

Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

PubMed

Kim, Yang-Hee; Tabata, Yasuhiko

2017-11-01

The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Maize arabinoxylan gels as protein delivery matrices.

PubMed

Berlanga-Reyes, Claudia M; Carvajal-Millán, Elizabeth; Lizardi-Mendoza, Jaime; Rascón-Chu, Agustin; Marquez-Escalante, Jorge A; Martínez-López, Ana Luisa

2009-04-08

The laccase induced gelation of maize bran arabinoxylans at 2.5% (w/v) in the presence of insulin or beta-lactoglobulin at 0.1% (w/v) was investigated. Insulin and beta-lacto-globulin did not modify either the gel elasticity (9 Pa) or the cross-links content (0.03 and 0.015 microg di- and triferulic acids/mg arabinoxylan, respectively). The protein release capability of the gel was also investigated. The rate of protein release from gels was dependent on the protein molecular weight. The apparent diffusion coefficient was 0.99 x 10(-7) and 0.79 x 10(-7) cm(2)/s for insulin (5 kDa) and beta-lactoglobulin (18 kDa), respectively. The results suggest that maize bran arabinoxylan gels can be potential candidates for the controlled release of proteins.

Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome.

PubMed

Kattah, Michael G; Malynn, Barbara A; Ma, Averil

2017-11-10

Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1β and IL-18. Inflammasome activation is critical for the host's defense against pathogens, but dysregulation of inflammasomes may contribute to the pathogenesis of multiple diseases. Ultimately, understanding how various ubiquitin interacting proteins control inflammatory signaling cascades could provide new pathways for therapeutic intervention. Here we review specific ubiquitin-modifying enzymes and ubiquitination events that orchestrate inflammatory responses, with an emphasis on the NLRP3 inflammasome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

PubMed

Streubel, A; Siepmann, J; Bodmeier, R

2003-01-01

The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating.

PubMed

Alejo, Teresa; Andreu, Vanesa; Mendoza, Gracia; Sebastian, Victor; Arruebo, Manuel

2018-08-01

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system. Copyright © 2018 Elsevier Inc. All rights reserved.

Mesoporous silica nanoparticle-based intelligent drug delivery system for bienzyme-responsive tumour targeting and controlled release.

PubMed

Zhang, Yang; Xu, Juan

2018-01-01

This paper proposes a novel type of multifunctional envelope-type mesoporous silica nanoparticle (MSN) to achieve cancer cell targeting and drug-controlled release. In this system, MSNs were first modified by active targeting moiety hyaluronic acid (HA) for breast cancer cell targeting and hyaluronidases (Hyal)-induced intracellular drug release. Then gelatin, a proteinaceous biopolymer, was grafted onto the MSNs to form a capping layer via glutaraldehyde-mediated cross-linking. To shield against unspecific uptake of cells and prolong circulation time, the nanoparticles were further decorated with poly(ethylene glycol) polymers (PEG) to obtain MSN@HA-gelatin-PEG (MHGP). Doxorubicin (DOX), as a model drug, was loaded into PEMSN to assess the breast cancer cell targeting and drug release behaviours. In vitro study revealed that PEG chains protect the targeting ligand and shield against normal cells. After reaching the breast cancer cells, MMP-2 overpressed by cells hydrolyses gelatin layer to deshield PEG and switch on the function of HA. As a result, DOX-loaded MHGP was selectively trapped by cancer cells through HA receptor-mediated endocytosis and subsequently release DOX due to Hyal-catalysed degradation of HA. This system presents successful bienzyme-responsive targeting drug delivery in an optimal fashion and provides potential applications for targeted cancer therapy.

Modulation of electrostatic interactions to improve controlled drug delivery from nanogels.

PubMed

Mauri, Emanuele; Chincarini, Giulia M F; Rigamonti, Riccardo; Magagnin, Luca; Sacchetti, Alessandro; Rossi, Filippo

2017-03-01

The synthesis of nanogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy in controlled drug delivery. However, with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small hydrophilic molecules through polymeric network pores. For these reasons research community is pointing toward the use of click strategies to reduce release rates of the linked drugs to the polymer chains. Here we propose an alternative method that considers the electrostatic interactions between polymeric chains and drugs to tune the release kinetics from nanogel network. The main advantage of these systems lies in the fact that the carried drugs are not modified and no chemical reactions take place during their loading and release. In this work we synthesized PEG-PEI based nanogels with different protonation degrees and the release kinetics with charged and uncharged drug mimetics (sodium fluorescein, SF, and rhodamine B, RhB) were studied. Moreover, also the effect of counterion used to induce protonation was taken into account in order to build a tunable drug delivery system able to provide multiple release rates with the same device. Copyright © 2016 Elsevier B.V. All rights reserved.

Algal antifouling and fouling-release properties of metal surfaces coated with a polymer inspired by marine mussels.

PubMed

Statz, Andrea; Finlay, John; Dalsin, Jeffrey; Callow, Maureen; Callow, James A; Messersmith, Phillip B

2006-01-01

The marine antifouling and fouling-release performance of titanium surfaces coated with a bio-inspired polymer was investigated. The polymer consisted of methoxy-terminated poly(ethylene glycol) (mPEG) conjugated to the adhesive amino acid l-3,4-dihydroxyphenylalanine (DOPA) and was chosen based on its successful resistance to protein and mammalian cell fouling. Biofouling assays for the settlement and release of the diatom Navicula perminuta and settlement, growth and release of zoospores and sporelings (young plants) of the green alga Ulva linza were carried out. Results were compared to glass, a poly(dimethylsiloxane) elastomer (Silastic T2) and uncoated Ti. The mPEG-DOPA3 modified Ti surfaces exhibited a substantial decrease in attachment of both cells of N. perminuta and zoospores of U. linza as well as the highest detachment of attached cells under flow compared to control surfaces. The superior performance of this polymer over a standard silicone fouling-release coating in diatom assays and approximately equivalent performance in zoospore assays suggests that this bio-inspired polymer may be effective in marine antifouling and fouling-release applications.

Proactive interference and item similarity in working memory.

PubMed

Bunting, Michael

2006-03-01

Proactive interference (PI) may influence the predictive utility of working memory span tasks. Participants in one experiment (N=70) completed Ravens Advanced Progressive Matrices (RAPM) and multiple versions of operation span and probed recall, modified for the type of memoranda (digits or words). Changing memoranda within- or across-trials released PI, but not doing so permitted PI buildup. Scores from PI-build trials, but not PI-release trials, correlated with RAPM and accounted for as much variance in RAPM as unmodified tasks. These results are consistent with controlled attention and inhibition accounts of working memory, and they elucidate a fundamental component of working memory span tasks.

Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

PubMed

Lipin, Mikhail Y; Vigh, Jozsef

2018-05-01

Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔV m ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina. Inner and outer retinal inhibition to Mbs was blocked with bath applied picrotoxin (PTX) and NBQX, respectively. Then, control and pharmacologically modified light responses were injected into axotomized Mb terminals as command potentials to induce voltage-gated Ca 2+ influx (Q Ca ) and consequent glutamate release. Stimulus-evoked glutamate release was quantified by the increase in membrane capacitance (ΔC m ). Increasing depolarization of Mb terminals upon removal of inner and outer retinal inhibition enhanced the ΔV m /Q Ca ratio equally at a given light intensity and inhibition did not alter the overall relation between Q Ca and ΔC m . However, relative to control, light responses recorded in the presence of PTX and PTX + NBQX increased ΔC m unevenly across different stimulus intensities: at dim stimulus intensities predominantly the inner retinal GABAergic inhibition controlled release from Mbs, whereas the inner and outer retinal inhibition affected release equally in response to bright stimuli. Furthermore, our results suggest that non-linear relationship between Q Ca and glutamate release can influence the efficacy of inner and outer retinal inhibitory pathways to mediate Mb output at different light intensities. © 2018 Wiley Periodicals, Inc.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Doxycycline-encapsulated nanotube-modified dentin adhesives.

PubMed

Feitosa, S A; Palasuk, J; Kamocki, K; Geraldeli, S; Gregory, R L; Platt, J A; Windsor, L J; Bottino, M C

2014-12-01

This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives-but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels-we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via β-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations. © International & American Associations for Dental Research.

Doxycycline-Encapsulated Nanotube-Modified Dentin Adhesives

PubMed Central

Feitosa, S.A.; Palasuk, J.; Kamocki, K.; Geraldeli, S.; Gregory, R.L.; Platt, J.A.; Windsor, L.J.; Bottino, M.C.

2014-01-01

This article presents details of fabrication, biological activity (i.e., anti–matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)–encapsulated halloysite nanotube (HNT)–modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives—but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels—we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via β-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations. PMID:25201918

A novel intracellular pH-responsive formulation for FTY720 based on PEGylated graphene oxide nano-sheets.

PubMed

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim; Karamyan, Ali; Omidfar, Kobra

2018-01-01

This study was performed to investigate a novel pH-responsive nanocarrier based on modified nano graphene oxide (nGO) to promote the acid-triggered intracellular release of a poorly soluble drug, FTY720. To synthesize a drug conjugated to modified nGO, first the polyethylene glycol (PEG) was conjugated to nGO, then the produced PEG-nGO was functionalized with the anticancer drug, FTY720, through amide bonding. It was characterized by the scanning electron microscopy (SEM), the atomic force microscopy (AFM), the Fourier transform infrared (FTIR) spectroscopy and the UV-vis spectroscopy. In vitro drug release of the FTY720-conjugated PEG-nGO was evaluated at pH 7.4 and 4.6 PBS at 37 °C. Furthermore, the antineoplastic action of unloaded and drug-loaded carrier against the human breast adenocarcinoma cell line MCF7 was explored using MTT and BrdU assays. Characterization methods indicated successful drug deposition on the surface of nGO. In vitro, drug release results revealed a significantly faster release of FTY720 from PEG-nGO at acidic pH, compared with physiological pH. The proliferation assays proved that the unloaded nGO had no significant cytotoxicity against MCF7 cells, while free FTY720- and FTY720-loaded PEG-nGO had an approximately equal cytotoxic effect on the MCF7 cells. It was found that the extended release characteristic of FTY720 was well fitted to Korsmeyer-Peppas model and the release profile of FTY720 from PEG-nGO is diffusion controlled. PEGylated GO can act as a pH-responsive drug carrier to improve the efficacy of anticancer drug delivery.

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites

PubMed Central

Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Background Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. Methods With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)–DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP–DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. Results SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. Conclusion A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings. PMID:29713169

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

PubMed

Yang, Yao-Yao; Liu, Zhe-Peng; Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)-DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP-DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells.

PubMed

Cai, Li-Li; Liu, Ping; Li, Xi; Huang, Xuan; Ye, Yi-Qing; Chen, Feng-Ying; Yuan, Hong; Hu, Fu-Qiang; Du, Yong-Zhong

2011-01-01

Solid tumors need new blood vessels to feed and nourish them as well as to allow tumor cells to escape into the circulation and lodge in other organs, which is termed "angiogenesis." Some tumor cells within solid tumors can overexpress integrins α(v)β(3) and α(v)β(5), which can specifically recognize the peptide motif Arg-Gly-Asp (RGD). Thus, the targeting of RGD-modified micelles to tumor vasculature is a promising strategy for tumor-targeting treatment. RGD peptide (GSSSGRGDSPA) was coupled to poly(ethylene glycol)-modified stearic acid-grafted chitosan (PEG-CS-SA) micelles via chemical reaction in the presence of N,N'-Disuccinimidyl carbonate. The critical micelle concentration of the polymeric micelles was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The micelle size, size distribution, and zeta potential were measured by light scattering and electrophoretic mobility. Doxorubicin (DOX) was chosen as a model anticancer drug to investigate the drug entrapment efficiency, in vitro drug-release profile, and in vitro antitumor activities of drug-loaded RGD-PEG-CS-SA micelles in cells that overexpress integrins (α(ν)β(3) and α(ν)β(5)) and integrin-deficient cells. Using DOX as a model drug, the drug encapsulation efficiency could reach 90%, and the in vitro drug-release profiles suggested that the micelles could be used as a controlled-release carrier for the hydrophobic drug. Qualitative and quantitative analysis of cellular uptake indicated that RGD-modified micelles could significantly increase the DOX concentration in integrin-overexpressing human hepatocellular carcinoma cell line (BEL-7402), but not in human epithelial carcinoma cell line (Hela). The competitive cellular-uptake test showed that the cellular uptake of RGD-modified micelles in BEL-7402 cells was significantly inhibited in the presence of excess free RGD peptides. In vitro cytotoxicity tests demonstrated DOX-loaded RGD-modified micelles could specifically enhance the cytotoxicity against BEL-7402 compared with DOX-loaded PEG-CS-SA and doxorubicin hydrochlorate. This study suggests that RGD-modified PEG-CS-SA micelles are promising drug carriers for integrin-overexpressing tumor active targeting therapy.

Magnetic pH-responsive poly(methacrylic acid-co-acrylic acid)-co-polyvinylpyrrolidone magnetic nano-carrier for controlled delivery of fluvastatin.

PubMed

Amoli-Diva, Mitra; Pourghazi, Kamyar; Mashhadizadeh, Mohammad Hossein

2015-02-01

A novel pH-responsive polymer, poly(methacrylic acid-co-acrylic acid)-co-polyvinyl-pyrrolidone (polymeric nano-carrier) was synthesized and used for encapsulation of 3-aminopropyl triethoxysilane modified Fe3O4 nanoparticles to prepare a new magnetic nano-carrier. The loading and release characteristics of both polymeric and magnetic nano-carriers were investigated using fluvastatin as the model drug. The loading behavior of the carriers was studied by varying concentration of fluvastatin in aqueous medium at 25°C and their release was followed spectrophotometrically (at 304 nm) at 37°C in three different solutions (buffered at pH1.2, 5.5 and 7.2) to simulate gastric and intestine medium. The effect of different parameters on the release of fluvastatin such as the amount of methacrylic acid monomer, cross-linker amount, initiator amount, and magnetic nanoparticles content was also studied. Considering the release kinetics and mechanism of the magnetic nanocarrier besides swelling behavior study of the polymeric nano-carrier reveal Fickian pattern and diffusion controlled mechanism for delivery of fluvastatin. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation development and release studies of indomethacin suppositories.

PubMed

Sah, M L; Saini, T R

2008-01-01

Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed apparatus. When surfactant was used in low concentration then release rate was much greater, as compared to high concentration. When stability studies were performed on the prepared indomethacin suppositories it was found that suppositories made by water-soluble base had no significant changes while suppositories prepared by oil soluble bases, had some signs of instability.

Characterization of nitric oxide-releasing microparticles for the mucosal delivery.

PubMed

Yoo, Jin-Wook; Lee, Jae-Suk; Lee, Chi H

2010-03-15

For the treatment of female sexual arousal disorder (FSAD), we developed microparticles made of PLGA containing nitric oxide (NO) donor (DETA NONOate) to efficiently deliver NO to vaginal mucosa. The NO-releasing microparticles were prepared by various emulsion methods. SEM and DSC studies were performed to examine the microparticles. The release studies were conducted under various conditions to optimize the loading dose in the microparticles. NO diffusivity through vaginal epithelial cells was evaluated and pharmacological activity of NO-releasing microparticles was examined by assessment of intracellular cGMP level in vaginal cells. Through the modified double emulsion solvent evaporation method (w/o/w(a)), the acid labile DETA NONOate was stabilized during the fabrication process and homogenous morphology and high entrapment efficiency were achieved. DETA NONOate was protected under the acidic conditions of the vagina and NO was released from the microparticles in a controlled manner. A significant amount of NO produced from DETA NONOate penetrated through the vaginal epithelial cells. The intracellular cGMP level increased with the treatment of NO-releasing microparticles in vaginal cells. These findings suggest that NO-releasing microparticles could improve the vaginal blood perfusion and open up the possibilities of novel treatment of FSAD. (c) 2009 Wiley Periodicals, Inc.

Infectious diseases: Surveillance, genetic modification and simulation

USGS Publications Warehouse

Koh, H. L.; Teh, S.Y.; De Angelis, D. L.; Jiang, J.

2011-01-01

Infectious diseases such as influenza and dengue have the potential of becoming a worldwide pandemic that may exert immense pressures on existing medical infrastructures. Careful surveillance of these diseases, supported by consistent model simulations, provides a means for tracking the disease evolution. The integrated surveillance and simulation program is essential in devising effective early warning systems and in implementing efficient emergency preparedness and control measures. This paper presents a summary of simulation analysis on influenza A (H1N1) 2009 in Malaysia. This simulation analysis provides insightful lessons regarding how disease surveillance and simulation should be performed in the future. This paper briefly discusses the controversy over the experimental field release of genetically modified (GM) Aedes aegypti mosquito in Malaysia. Model simulations indicate that the proposed release of GM mosquitoes is neither a viable nor a sustainable control strategy. ?? 2011 WIT Press.

Fabrication and Modification of Nanoporous Silicon Particles

NASA Technical Reports Server (NTRS)

Ferrari, Mauro; Liu, Xuewu

2010-01-01

Silicon-based nanoporous particles as biodegradable drug carriers are advantageous in permeation, controlled release, and targeting. The use of biodegradable nanoporous silicon and silicon dioxide, with proper surface treatments, allows sustained drug release within the target site over a period of days, or even weeks, due to selective surface coating. A variety of surface treatment protocols are available for silicon-based particles to be stabilized, functionalized, or modified as required. Coated polyethylene glycol (PEG) chains showed the effective depression of both plasma protein adsorption and cell attachment to the modified surfaces, as well as the advantage of long circulating. Porous silicon particles are micromachined by lithography. Compared to the synthesis route of the nanomaterials, the advantages include: (1) the capability to make different shapes, not only spherical particles but also square, rectangular, or ellipse cross sections, etc.; (2) the capability for very precise dimension control; (3) the capacity for porosity and pore profile control; and (4) allowance of complex surface modification. The particle patterns as small as 60 nm can be fabricated using the state-of-the-art photolithography. The pores in silicon can be fabricated by exposing the silicon in an HF/ethanol solution and then subjecting the pores to an electrical current. The size and shape of the pores inside silicon can be adjusted by the doping of the silicon, electrical current application, the composition of the electrolyte solution, and etching time. The surface of the silicon particles can be modified by many means to provide targeted delivery and on-site permanence for extended release. Multiple active agents can be co-loaded into the particles. Because the surface modification of particles can be done on wafers before the mechanical release, asymmetrical surface modification is feasible. Starting from silicon wafers, a treatment, such as KOH dipping or reactive ion etching (RIE), may be applied to make the surface rough. This helps remove the nucleation layer. A protective layer is then deposited on the wafer. The protective layer, such as silicon nitride film or photoresist film, protects the wafer from electrochemical etching in an HF-based solution. A lithography technique is applied to pattern the particles onto the protective film. The undesired area of the protective film is removed, and the protective film on the back side of the wafer is also removed. Then the pattern is exposed to HF/surfactant solution, and a larger DC electrical current is applied to the wafers for a selected time. This step removes the nucleation layer. Then a DC current is applied to generate the nanopores. Next, a large electrical current is applied to generate a release layer. The particles are mechanically suspended in the solvent and collected by filtration or centrifuge.

Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate.

PubMed

Amrutkar, P P; Chaudhari, P D; Patil, S B

2012-01-01

Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes.

PubMed

Bertrand, Nicolas; Simard, Pierre; Leroux, Jean-Christophe

2017-01-01

pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles, and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of the lysosomes.Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0 to 5.5 can be easily prepared by inserting a hydrophobically modified N-isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co-MAA)) in the lipid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation and characterization of large unilamellar pH-sensitive vesicles.

pH-Switchable Interaction of a Carboxybetaine Ester-Based SAM with DNA and Gold Nanoparticles.

PubMed

Filip, Jaroslav; Popelka, Anton; Bertok, Tomas; Holazova, Alena; Osicka, Josef; Kollar, Jozef; Ilcikova, Marketa; Tkac, Jan; Kasak, Peter

2017-07-11

We describe a self-assembled monolayer (SAM) on a gold surface with a carboxybetaine ester functionality to control the interaction between DNA and gold nanoparticles via pH. The negatively charged phosphate backbone of DNA interacts with and adsorbs to the positively charged carboxybetaine esters on the SAM. DNA release can be achieved by the hydrolysis of carboxybetaine ester (CBE) to a zwitterionic carboxybetaine state. Furthermore, the adsorption of negatively charged citrate-capped gold nanoparticles to a SAM-modified plain gold surface can be controlled by the pH. The SAM based on carboxybetaine ester allows for the homogeneous adsorption of particles, whereas the SAM after hydrolysis at high pH repels AuNP adsorption. The antifouling surface properties of the surface modified with carboxybetaine were investigated with protein samples.

Geo-engineering experiments in two urban ponds to control eutrophication.

PubMed

Waajen, Guido; van Oosterhout, Frank; Douglas, Grant; Lürling, Miquel

2016-06-15

Many urban ponds experience detrimental algal blooms as the result of eutrophication. During a two year field experiment, the efficacy of five in situ treatments to mitigate eutrophication effects in urban ponds was studied. The treatments targeted the sediment phosphorus release and were intended to switch the ponds from a turbid phytoplankton-dominated state to a clear-water state with a low phytoplankton biomass. Two eutrophic urban ponds were each divided into six compartments (300-400 m(2); 210-700 m(3)). In each pond the following treatments were tested: dredging in combination with biomanipulation (involving fish biomass control and the introduction of macrophytes) with and without the addition of the flocculant polyaluminiumchloride, interception and reduction of sediment phosphorus release with lanthanum-modified bentonite (Phoslock(®)) in combination with biomanipulation with and without polyaluminiumchloride; biomanipulation alone; and a control. Trial results support the hypothesis that the combination of biomanipulation and measures targeting the sediment phosphorus release can be effective in reducing the phytoplankton biomass and establishing and maintaining a clear-water state, provided the external phosphorus loading is limited. During the experimental period dredging combined with biomanipulation showed mean chlorophyll-a concentrations of 5.3 and 6.2 μg L(-1), compared to 268.9 and 52.4 μg L(-1) in the control compartments. Lanthanum-modified bentonite can be an effective alternative to dredging and in combination with biomanipulation it showed mean chlorophyll-a concentrations of 5.9 and 7.6 μg L(-1). Biomanipulation alone did not establish a clear-water state or only during a limited period. As the two experimental sites differed in their reaction to the treatments, it is important to choose the most promising treatment depending on site specific characteristics. In recovering the water quality status of urban ponds, continuing attention is required to the concurrent reduction of external phosphorus loading and to maintaining an appropriate fish community. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electrochemically controlled drug-mimicking protein release from iron-alginate thin-films associated with an electrode.

PubMed

Jin, Zhiyuan; Güven, Güray; Bocharova, Vera; Halámek, Jan; Tokarev, Ihor; Minko, Sergiy; Melman, Artem; Mandler, Daniel; Katz, Evgeny

2012-01-01

Novel biocompatible hybrid-material composed of iron-ion-cross-linked alginate with embedded protein molecules has been designed for the signal-triggered drug release. Electrochemically controlled oxidation of Fe(2+) ions in the presence of soluble natural alginate polymer and drug-mimicking protein (bovine serum albumin, BSA) results in the formation of an alginate-based thin-film cross-linked by Fe(3+) ions at the electrode interface with the entrapped protein. The electrochemically generated composite thin-film was characterized by electrochemistry and atomic force microscopy (AFM). Preliminary experiments demonstrated that the electrochemically controlled deposition of the protein-containing thin-film can be performed at microscale using scanning electrochemical microscopy (SECM) as the deposition tool producing polymer-patterned spots potentially containing various entrapped drugs. Application of reductive potentials on the modified electrode produced Fe(2+) cations which do not keep complexation with alginate, thus resulting in the electrochemically triggered thin-film dissolution and the protein release. Different experimental parameters, such as the film-deposition time, concentrations of compounds and applied potentials, were varied in order to demonstrate that the electrodepositon and electrodissolution of the alginate composite film can be tuned to the optimum performance. A statistical modeling technique was applied to find optimal conditions for the formation of the composite thin-film for the maximal encapsulation and release of the drug-mimicking protein at the lowest possible potential. © 2011 American Chemical Society

Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PubMed

Attama, A A; Reichl, S; Müller-Goymann, C C

2009-08-01

The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.

Introducing a decomposition rate modifier in the Rothamsted Carbon Model to predict soil organic carbon stocks in saline soils.

PubMed

Setia, Raj; Smith, Pete; Marschner, Petra; Baldock, Jeff; Chittleborough, David; Smith, Jo

2011-08-01

Soil organic carbon (SOC) models such as the Rothamsted Carbon Model (RothC) have been used to estimate SOC dynamics in soils over different time scales but, until recently, their ability to accurately predict SOC stocks/carbon dioxide (CO(2)) emissions from salt-affected soils has not been assessed. Given the large extent of salt-affected soils (19% of the 20.8 billion ha of arable land on Earth), this may lead to miss-estimation of CO(2) release. Using soils from two salt-affected regions (one in Punjab, India and one in South Australia), an incubation study was carried out measuring CO(2) release over 120 days. The soils varied both in salinity (measured as electrical conductivity (EC) and calculated as osmotic potential using EC and water content) and sodicity (measured as sodium adsorption ratio, SAR). For soils from both regions, the osmotic potential had a significant positive relationship with CO(2)-C release, but no significant relationship was found between SAR and CO(2)-C release. The monthly cumulative CO(2)-C was simulated using RothC. RothC was modified to take into account reductions in plant inputs due to salinity. A subset of non-salt-affected soils was used to derive an equation for a "lab-effect" modifier to account for changes in decomposition under lab conditions and this modifier was significantly related with pH. Using a subset of salt-affected soils, a decomposition rate modifier (as a function of osmotic potential) was developed to match measured and modelled CO(2)-C release after correcting for the lab effect. Using this decomposition rate modifier, we found an agreement (R(2) = 0.92) between modelled and independently measured data for a set of soils from the incubation experiment. RothC, modified by including reduced plant inputs due to salinity and the salinity decomposition rate modifier, was used to predict SOC stocks of soils in a field in South Australia. The predictions clearly showed that SOC stocks are reduced in saline soils. Therefore both the decomposition rate modifier and plant input modifier should be taken into account when accounting for SOC turnover in saline soils. Since modeling has previously not accounted for the impact of salinity, our results suggest that previous predictions may have overestimated SOC stocks.

Antifungal nanofibers made by controlled release of sea animal derived peptide

NASA Astrophysics Data System (ADS)

Viana, Juliane F. C.; Carrijo, Jéssica; Freitas, Camila G.; Paul, Arghya; Alcaraz, Jarib; Lacorte, Cristiano C.; Migliolo, Ludovico; Andrade, César A.; Falcão, Rosana; Santos, Nuno C.; Gonçalves, Sónia; Otero-González, Anselmo J.; Khademhosseini, Ali; Dias, Simoni C.; Franco, Octávio L.

2015-03-01

Candida albicans is a common human-pathogenic fungal species with the ability to cause several diseases including surface infections. Despite the clear difficulties of Candida control, antimicrobial peptides (AMPs) have emerged as an alternative strategy for fungal control. In this report, different concentrations of antifungal Cm-p1 (Cencritchis muricatus peptide 1) were electrospun into nanofibers for drug delivery. The nanofibers were characterized by mass spectrometry confirming the presence of the peptide on the scaffold. Atomic force microscopy and scanning electronic microscopy were used to measure the diameters, showing that Cm-p1 affects fiber morphology as well as the diameter and scaffold thickness. The Cm-p1 release behavior from the nanofibers demonstrated peptide release from 30 min to three days, leading to effective yeast control in the first 24 hours. Moreover, the biocompatibility of the fibers were evaluated through a MTS assay as well as ROS production by using a HUVEC model, showing that the fibers do not affect cell viability and only nanofibers containing 10% Cm-p1-PVA improved ROS generation. In addition, the secretion of pro-inflammatory cytokines IL-6 and TNF-α by the HUVECs was also slightly modified by the 10% Cm-p1-PVA nanofibers. In conclusion, the electrospinning technique applied here allowed for the manufacture of biodegradable biomimetic nanofibrous extracellular membranes with the ability to control fungal infection.Candida albicans is a common human-pathogenic fungal species with the ability to cause several diseases including surface infections. Despite the clear difficulties of Candida control, antimicrobial peptides (AMPs) have emerged as an alternative strategy for fungal control. In this report, different concentrations of antifungal Cm-p1 (Cencritchis muricatus peptide 1) were electrospun into nanofibers for drug delivery. The nanofibers were characterized by mass spectrometry confirming the presence of the peptide on the scaffold. Atomic force microscopy and scanning electronic microscopy were used to measure the diameters, showing that Cm-p1 affects fiber morphology as well as the diameter and scaffold thickness. The Cm-p1 release behavior from the nanofibers demonstrated peptide release from 30 min to three days, leading to effective yeast control in the first 24 hours. Moreover, the biocompatibility of the fibers were evaluated through a MTS assay as well as ROS production by using a HUVEC model, showing that the fibers do not affect cell viability and only nanofibers containing 10% Cm-p1-PVA improved ROS generation. In addition, the secretion of pro-inflammatory cytokines IL-6 and TNF-α by the HUVECs was also slightly modified by the 10% Cm-p1-PVA nanofibers. In conclusion, the electrospinning technique applied here allowed for the manufacture of biodegradable biomimetic nanofibrous extracellular membranes with the ability to control fungal infection. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00767d

Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

PubMed

Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

2017-10-26

Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

Routine HIV screening in North Carolina in the era of the Affordable Care Act: update on laws, reimbursement, and tests.

PubMed

White, Becky L; Carter, Yvonne L; Records, Katherine; Martin, Ian B K

2013-11-01

Eighteen percent of the 1.2 million human immunodeficiency virus (HIV)-infected individuals in the United States are undiagnosed, with North Carolina accounting for the eighth largest number of new HIV diagnoses in 2011. In an effort to identify more HIV-infected individuals by reducing physician barriers to HIV testing, the Centers for Disease Control and Prevention have expanded their HIV screening recommendations to adolescents and adults without HIV risk factors or behaviors, eliminated federal requirements for pretest counseling, and modified the informed consent process. In 2010, the Office of National AIDS (acquired immunodeficiency syndrome) Policy released the first-ever national HIV/AIDS strategy, with the goal of reducing new infections, increasing access to care, improving HIV outcomes, and reducing HIV racial/ethnic disparities. In 2013, the US Preventive Services Task Force released A-level recommendations recommending nonrisk-based HIV screening for adults and adolescents that are consistent with the recommendations of the Centers for Disease Control and Prevention. In concert with these federal recommendations, the majority of states have modified their consent and counseling requirements. The implementation of the Patient Protection and Affordable Care Act will add requirements and incentives for federal (Medicare), state (Medicaid), and private (insurance) payers to reimburse physicians and patients for nonrisk-based HIV screening.

Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.

PubMed

Di Nardo, Anna; Holmes, Anna D; Muto, Yumiko; Huang, Eugene Y; Preston, Norman; Winkelman, Warren J; Gallo, Richard L

2016-06-01

Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear. We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea. In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients. Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group. Healthy control subjects were not studied. Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Extending the shelf life of edible flowers with controlled release of 1-methylcyclopropene and modified atmosphere packaging.

PubMed

Kou, Liping; Turner, Ellen R; Luo, Yaguang

2012-05-01

Edible flowers have great sensory appeal, but their extremely short shelf life limits their commercial usage. Postharvest 1-methylcyclopropene (1-MCP) treatment is used to counter ethylene activity and delay senescence in fresh produce; however, its potential application in edible flowers has not been tested. The objective of this study was to investigate the effect of 1-MCP treatment with modified atmosphere packaging (MAP) on the shelf life of edible flowers. Freshly harvested carnations and snapdragons were packaged in trays with or without 0.5 μL/L of 1-MCP, sealed with a gas permeable film, and stored at 5 °C. Package atmospheres, tissue electrolyte leakage, and flower quality were evaluated on days 0, 7, and 14. Treatment with 1-MCP resulted in significantly slower changes in package headspace O(2), CO(2), and C(2)H(4) partial pressures, maintained higher overall quality of both flower species and reduced electrolyte leakage and abscission in snapdragon. All samples prepared with MAP had significantly reduced dehydration and higher overall quality compared to flowers packaged commercially in plastic clamshell containers. Treatments with controlled release of 1-MCP and MAP significantly extended storage life of edible carnation and snapdragon flowers. © 2012 Institute of Food Technologists®

Effects of coating materials on nanoindentation hardness of enamel and adjacent areas.

PubMed

Alsayed, Ehab Z; Hariri, Ilnaz; Nakashima, Syozi; Shimada, Yasushi; Bakhsh, Turki A; Tagami, Junji; Sadr, Alireza

2016-06-01

Materials that can be applied as thin coatings and actively release fluoride or other bioavailable ions for reinforcing dental hard tissue deserve further investigation. In this study we assessed the potential of resin coating materials in protection of underlying and adjacent enamel against demineralization challenge using nanoindentation. Enamel was coated using Giomer (PRG Barrier Coat, PBC), resin-modified glass-ionomer (Clinpro XT Varnish, CXT), two-step self-etch adhesive (Clearfil SE Protect, SEP) or no coating (control). After 5000 thermal cycles and one-week demineralization challenge, Martens hardness of enamel beneath the coating, uncoated area and intermediate areas was measured using a Berkovich tip under 2mN load up to 200μm depth. Integrated hardness and 10-μm surface zone hardness were compared among groups. Nanoindentation and scanning electron microscopy suggested that all materials effectively prevented demineralization in coated area. Uncoated areas presented different hardness trends; PBC showed a remarkable peak at the surface zone before reaching as low as the control, while CXT showed relatively high hardness values at all depths. Ion-release from coating materials affects different layers of enamel. Coatings with fluoride-releasing glass fillers contributed to reinforcement of adjacent enamel. Surface prereacted glass filler-containing PBC superficially protected neighboring enamel against demineralization, while resin-modified glass-ionomer with calcium (CXT) improved in-depth protection. Cross-sectional hardness mapping of enamel on a wide range of locations revealed minute differences in its structure. Copyright © 2016 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Terminology challenges: defining modified release dosage forms in veterinary medicine.

PubMed

Martinez, Marilyn N; Lindquist, Danielle; Modric, Sanja

2010-08-01

Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells

PubMed Central

Zhang, Jinming; Wang, Lu; Fai Chan, Hon; Xie, Wei; Chen, Sheng; He, Chengwei; Wang, Yitao; Chen, Meiwan

2017-01-01

One of the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance the cancer cellular internalization and implement the controlled drug release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated to coload paclitaxel (PTX) and tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX was covalently conjugated to poly (D,L-lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET was physically capsulated spontaneously for the aim to suppress P-gp in advance by the earlier released TET in cancer cells. As a result, the PTX+TET/iRGD LPNs with a core-shell structure possessed high drug loading efficiency, stability and redox-sensitive drug release profiles. Owing to the enhanced cellular uptake and P-gp suppression mediated by TET, significantly more PTX accumulated in A2780/PTX cells treated with PTX+TET/iRGD LPNs than either free drugs or non-iRGD modified LPNs. As expected, PTX+TET/iRGD LPNs presented the highest cytotoxicity against A2780/PTX cells and effectively promoted ROS production, enhanced apoptosis and cell cycle arrests particularly. Taken together, the co-delivery system demonstrated great promise as potential treatment for MDR-related tumors based on the synergistic effects of P-gp inhibition, enhanced endocytosis and intracellular sequentially drug release. PMID:28470171

Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction.

PubMed

Saveliev, Anatoly; Khuzakhmetova, Venera; Samigullin, Dmitry; Skorinkin, Andrey; Kovyazina, Irina; Nikolsky, Eugeny; Bukharaeva, Ellya

2015-10-01

The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions' entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings.

Copper Metal-Organic Framework Nanoparticles Stabilized with Folic Acid Improve Wound Healing in Diabetes.

PubMed

Xiao, Jisheng; Zhu, Yunxiao; Huddleston, Samantha; Li, Peng; Xiao, Baixue; Farha, Omar K; Ameer, Guillermo A

2018-02-27

The successful treatment of chronic nonhealing wounds requires strategies that promote angiogenesis, collagen deposition, and re-epithelialization of the wound. Copper ions have been reported to stimulate angiogenesis; however, several applications of copper salts or oxides to the wound bed are required, leading to variable outcomes and raising toxicity concerns. We hypothesized that copper-based metal-organic framework nanoparticles (Cu-MOF NPs), referred to as HKUST-1, which are rapidly degraded in protein solutions, can be modified to slowly release Cu 2+ , resulting in reduced toxicity and improved wound healing rates. Folic acid was added during HKUST-1 synthesis to generate folic-acid-modified HKUST-1 (F-HKUST-1). The effect of folic acid incorporation on NP stability, size, hydrophobicity, surface area, and copper ion release profile was measured. In addition, cytotoxicity and in vitro cell migration processes due to F-HKUST-1 and HKUST-1 were evaluated. Wound closure rates were assessed using the splinted excisional dermal wound model in diabetic mice. The incorporation of folic acid into HKUST-1 enabled the slow release of copper ions, which reduced cytotoxicity and enhanced cell migration in vitro. In vivo, F-HKUST-1 induced angiogenesis, promoted collagen deposition and re-epithelialization, and increased wound closure rates. These results demonstrate that folic acid incorporation into HKUST-1 NPs is a simple, safe, and promising approach to control Cu 2+ release, thus enabling the direct application of Cu-MOF NPs to wounds.

Modified tricalcium silicate cement formulations with added zirconium oxide.

PubMed

Li, Xin; Yoshihara, Kumiko; De Munck, Jan; Cokic, Stevan; Pongprueksa, Pong; Putzeys, Eveline; Pedano, Mariano; Chen, Zhi; Van Landuyt, Kirsten; Van Meerbeek, Bart

2017-04-01

This study aims to investigate the effect of modifying tricalcium silicate (TCS) cements on three key properties by adding ZrO 2 . TCS powders were prepared by adding ZrO 2 at six different concentrations. The powders were mixed with 1 M CaCl 2 solution at a 3:1 weight ratio. Biodentine (contains 5 wt.% ZrO 2 ) served as control. To evaluate the potential effect on mechanical properties, the mini-fracture toughness (mini-FT) was measured. Regarding bioactivity, Ca release was assessed using ICP-AES. The component distribution within the cement matrix was evaluated by Feg-SEM/EPMA. Cytotoxicity was assessed using an XTT assay. Adding ZrO 2 to TCS did not alter the mini-FT (p = 0.52), which remained in range of that of Biodentine (p = 0.31). Ca release from TSC cements was slightly lower than that from Biodentine at 1 day (p > 0.05). After 1 week, Ca release from TCS 30 and TCS 50 increased to a level that was significantly higher than that from Biodentine (p < 0.05). After 1 month, Ca release all decreased (p < 0.05), yet TCS 0 and TCS 50 released comparable amounts of Ca as at 1 day (p > 0.05). EPMA revealed a more even distribution of ZrO 2 within the TCS cements. Particles with an un-reacted core were surrounded by a hydration zone. The 24-, 48-, and 72-h extracts of TCS 50 were the least cytotoxic. ZrO 2 can be added to TCS without affecting the mini-FT; Ca release was reduced initially, to reach a prolonged release thereafter; adding ZrO 2 made TCS cements more biocompatible. TCS 50 is a promising cement formulation to serve as a biocompatible hydraulic calcium silicate cement.

Functionalized Polymeric Membrane with Enhanced Mechanical and Biological Properties to Control the Degradation of Magnesium Alloy.

PubMed

Wong, Hoi Man; Zhao, Ying; Leung, Frankie K L; Xi, Tingfei; Zhang, Zhixiong; Zheng, Yufeng; Wu, Shuilin; Luk, Keith D K; Cheung, Kenneth M C; Chu, Paul K; Yeung, Kelvin W K

2017-04-01

To achieve enhanced biological response and controlled degradation of magnesium alloy, a modified biodegradable polymer coating called polycaprolactone (PCL) is fabricated by a thermal approach in which the heat treatment neither alters the chemical composition of the PCL membrane nor the rate of magnesium ion release, pH value, or weight loss, compared with the untreated sample. The changes in the crystallinity, hydrophilicity, and oxygen content of heat-treated PCL coating not only improve the mechanical adhesion strength between the coating and magnesium substrate but also enhance the biological properties. Moreover, the thermally modified sample can lead to higher spreading and elongation of osteoblasts, due to the enhanced hydrophilicity and CO to CO functional group ratio. In the analyses of microcomputed tomography from one to four weeks postoperation, the total volume of new bone formation on the heat-treated sample is 10%-35% and 70%-90% higher than that of the untreated and uncoated controls, respectively. Surprisingly, the indentation modulus of the newly formed bone adjacent to the heat-treated sample is ≈20% higher than that of both controls. These promising results reveal the clinical potential of the modified PCL coating on magnesium alloy in orthopedic applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Twenty five years follow up of MB leprosy patients retreated with a modified MDT regimen after a full course of dapsone mono-therapy.

PubMed

Jing, Zhichun; Zhang, Renbao; Zhou, Doahai; Chen, Jiakeun

2009-06-01

The relentless emergence of dapsone resistance amongst M. leprae threatened leprosy control programmes, and increased the relapse rate of patients cured with dapsone monotherapy. The study aimed to analyse the effect on the relapse rate of dapsone-cured multibacillary (MB) leprosy patients, of re-treatment, using a multidrug therapy (MDT) regimen which differed from the WHO recommended regimen. 794 MB leprosy patients who had been released from treatment after dapsone monotherapy were selected, amongst them 657 were re-treated for 1 year using the modified multidrug therapy regimen (mMDT) including rifampicin, clofazimine and dapsone, and 137 patients were observed as control cases. The regimen was well tolerated with good compliance: 620 patients completed re-treatment with mild side effects and a low incidence of leprosy reactions. There was a statistically significant difference between the relapse rates of re-treated and control groups (chi squaredf = 57.44, P < 0.001). Furthermore, the relapses in the re-treated group were significantly more likely to be later than those in the control group (t = 25.62, P < 0.001). Re-treatment with this modified regimen is acceptable and can reduce the risk of early relapse in dapsone-cured patients. The problem of persisters causing late relapse is likely to remain.

Effect of novel chitosan-fluoroaluminosilicate resin modified glass ionomer cement supplemented with translationally controlled tumor protein on pulp cells.

PubMed

Wanachottrakul, Nattaporn; Chotigeat, Wilaiwan; Kedjarune-Leggat, Ureporn

2014-04-01

Dental materials that can promote cell proliferation and function is required for regenerative pulp therapy. Resin modified glass ionomer cement (RMGIC), a broadly used liner or restorative material, can cause apoptosis to pulp cells mainly due to HEMA (2-hydroxyethyl methacrylate), the released residual monomer. Recent studies found that chitosan and albumin could promote release of protein in GIC while translationally controlled tumor protein (TCTP) has an anti-apoptotic activity against HEMA. The aim of this study was to examine the effect of chitosan and albumin modified RMGIC (Exp-RMGIC) supplemented with TCTP on pulp cell viability and mineralization. Exp-RMGIC+TCTP was composed of RMGIC powder incorporated with 15 % of chitosan, 5 % albumin and supplemented with TCTP mixed with the same liquid components of RMGIC. The effect of each specimen on pulp cells was examined using the Transwell plate. From the MTT assay, Exp-RMGIC+TCTP had the highest percentages of viable cells (P < 0.05) at both 24 and 74 h. Flow cytometry revealed that, after 24 h, Exp-RMGIC+TCTP gave the lowest percentages of apoptotic cells compared to other groups. There was no difference in alkaline phosphatase (ALP) activity among different formula of the specimens, while cells cultured in media with TCTP had higher ALP activity. Von Kossa staining revealed that RMGIC+TCTP, and Exp-RMGIC+TCTP had higher percentages of calcium deposit area compared to those without TCTP. It was concluded that Exp-RMGIC supplemented with TCTP had less cytotoxicity than RMGIC and can protect cells from apoptosis better than RMGIC supplemented with TCTP.

Impact of physicochemical properties of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond on drug loading and release behavior

NASA Astrophysics Data System (ADS)

Numpilai, Thanapha; Witoon, Thongthai; Chareonpanich, Metta; Limtrakul, Jumras

2017-02-01

The conjugation of dexamethasone (DEX) onto modified-porous silica materials via a pH-responsive hydrazone bond has been reported to be highly efficient method to specifically deliver the DEX to diseased sites. However, the influence of physicochemical properties of porous silica materials has not yet been fully understood. In this paper, the impact of pore sizes, particle sizes and silanol contents on surface functionalization, drug loading and release behavior of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond was investigated. The grafting density was found to relate to the number of silanol groups on the surface of porous silica materials. The particle size and macropores of the porous silica materials played an vital role on the drug loading and release behavior. Although the porous silica materials with larger particle sizes possessed a lower grafting density, a larger amount of drug loading could be achieved. Moreover, the porous silica materials with larger particle sizes showed a slower release rate of DEX due to a longer distance for cleaved DEX diffusion out of pores. DEX release rate exhibited pH-dependent, sustained release. At pH 4.5, the amount of DEX release within 10 days could be controlled in the range of 12.74-36.41%, depending on the host material. Meanwhile, less than 1.5% of DEX was released from each of type of the porous silica materials at pH 7.4. The results of silica dissolution suggested that the degradation of silica matrix did not significantly affect the release rate of DEX. In addition, the kinetic modeling studies revealed that the DEX releases followed Korsmeyer-Peppas model with a release exponent (n) ranged from 0.3 to 0.47, indicating a diffusion-controlled release mechanism.

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

Kicker, Dwayne Curtis; Herrick, Courtney G; Zeitler, Todd

The numerical code DRSPALL (from direct release spallings) is written to calculate the volume of Waste Isolation Pilot Plant solid waste subject to material failure and transport to the surface (i.e., spallings) as a result of a hypothetical future inadvertent drilling intrusion into the repository. An error in the implementation of the DRSPALL finite difference equations was discovered and documented in a software problem report in accordance with the quality assurance procedure for software requirements. This paper describes the corrections to DRSPALL and documents the impact of the new spallings data from the modified DRSPALL on previous performance assessment calculations.more » Updated performance assessments result in more simulations with spallings, which generally translates to an increase in spallings releases to the accessible environment. Total normalized radionuclide releases using the modified DRSPALL data were determined by forming the summation of releases across each potential release pathway, namely borehole cuttings and cavings releases, spallings releases, direct brine releases, and transport releases. Because spallings releases are not a major contributor to the total releases, the updated performance assessment calculations of overall mean complementary cumulative distribution functions for total releases are virtually unchanged. Therefore, the corrections to the spallings volume calculation did not impact Waste Isolation Pilot Plant performance assessment calculation results.« less

Cell-surface engineering by a conjugation-and-release approach based on the formation and cleavage of oxime linkages upon mild electrochemical oxidation and reduction.

PubMed

Pulsipher, Abigail; Dutta, Debjit; Luo, Wei; Yousaf, Muhammad N

2014-09-01

We report a strategy to rewire cell surfaces for the dynamic control of ligand composition on cell membranes and the modulation of cell-cell interactions to generate three-dimensional (3D) tissue structures applied to stem-cell differentiation, cell-surface tailoring, and tissue engineering. We tailored cell surfaces with bioorthogonal chemical groups on the basis of a liposome-fusion and -delivery method to create dynamic, electroactive, and switchable cell-tissue assemblies through chemistry involving chemoselective conjugation and release. Each step to modify the cell surface: activation, conjugation, release, and regeneration, can be monitored and modulated by noninvasive, label-free analytical techniques. We demonstrate the utility of this methodology by the conjugation and release of small molecules to and from cell surfaces and by the generation of 3D coculture spheroids and multilayered cell tissues that can be programmed to undergo assembly and disassembly on demand. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Water temperature effects from simulated changes to dam operations and structures in the Middle and South Santiam Rivers, Oregon

USGS Publications Warehouse

Buccola, Norman L.

2017-05-31

Green Peter and Foster Dams on the Middle and South Santiam Rivers, Oregon, have altered the annual downstream water temperature profile (cycle). Operation of the dams has resulted in cooler summer releases and warmer autumn releases relative to pre-dam conditions, and that alteration can hinder recovery of various life stages of threatened spring-run Chinook salmon (Oncorhyncus tshawytscha) and winter steelhead (O. mykiss). Lake level management and the use of multiple outlets from varying depths at the dams can enable the maintenance of a temperature regime more closely resembling that in which the fish evolved by releasing warm surface water during summer and cooler, deeper water in the autumn. At Green Peter and Foster Dams, the outlet configuration is such that temperature control is often limited by hydropower production at the dams. Previously calibrated CE-QUAL-W2 water temperature models of Green Peter and Foster Lakes were used to simulate the downstream thermal effects from hypothetical structures and modified operations at the dams. Scenarios with no minimum power production requirements allowed some releases through shallower and deeper outlets (summer and autumn) to achieve better temperature control throughout the year and less year-to-year variability in autumn release temperatures. Scenarios including a hypothetical outlet floating 1 meter below the lake surface resulted in greater ability to release warm water during summer compared to existing structures. Later in Autumn (October 15–December 31), a limited amount of temperature control was realized downstream from Foster Dam by scenarios limited to operational changes with existing structures, resulting in 15-day averages within 1.0 degree Celsius of current operations.

Studies on the mechanism of endogenous pyrogen production. II. Role of cell products in the regulation of pyrogen release from blood leukocytes.

PubMed

Bodel, P

1974-09-01

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever.

Studies on the Mechanism of Endogenous Pyrogen Production II. Role of Cell Products in the Regulation of Pyrogen Release from Blood Leukocytes

PubMed Central

Bodel, Phyllis

1974-01-01

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever. PMID:4426696

Hybrid hydrogels produced by ionizing radiation technique

NASA Astrophysics Data System (ADS)

Oliveira, M. J. A.; Amato, V. S.; Lugão, A. B.; Parra, D. F.

2012-09-01

The interest in biocompatible hydrogels with particular properties has increased considerably in recent years due to their versatile applications in biomedicine, biotechnology, pharmacy, agriculture and controlled release of drugs. The use of hydrogels matrices for particular drug-release applications has been investigated with the synthesis of modified polymeric hydrogel of PVAl and 0.5, 1.0, 1.5% nano-clay. They were processed using gamma radiation from Cobalt-60 source at 25 kGy dose. The characterization of the hydrogels was conducted and toxicity was evaluated. The dried hydrogel was analyzed for thermogravimetry analysis (TGA), infrared spectroscopy (FTIR) and swelling in solutions of different pH. The membranes have no toxicity. The nano-clay influences directly the equilibrium swelling.

Fast synthesis, formation mechanism, and control of shell thickness of CuS–polystyrene core–shell microspheres

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

Zhao, Li-min, E-mail: zhaolimin@lcu.ecu.cn; Shao, Xin; Yin, Yi-bin

2012-09-15

Graphical abstract: Core–shell structure PSt/CuS were prepared using polystyrene which were modified by 3-methacryloxypropyltrimethoxysilane as template. The coating thickness of CuS can be controlled by the amount of 3-methacryloxypropyltrimethoxysilane and the UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS. Highlights: ► Core–shell structure PSt/CuS were prepared using silanol-modified polystyrene microspheres as template. ► The coating thickness of core–shell structure PSt/CuS can be controlled by a simple method. ► The UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS. -- Abstract: The silanol-modified polystyrene microspheres were prepared through dispersion polymerization.more » Then copper sulfide particles were grown on silanol-modified polystyrene through sonochemical deposition in an aqueous bath containing copper acetate and sulfide, released through the hydrolysis of thioacetamide. The resulting particles were continuous and uniform as characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared, thermogravimetric analysis and UV–vis absorption spectroscopy were used to characterize the structure and properties of core–shell particles. The results showed the coating thickness of CuS shell can be controlled by the amount of silanol and the UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS.« less

Awareness and support of release of genetically modified "sterile" mosquitoes, Key West, Florida, USA.

PubMed

Ernst, Kacey C; Haenchen, Steven; Dickinson, Katherine; Doyle, Michael S; Walker, Kathleen; Monaghan, Andrew J; Hayden, Mary H

2015-02-01

After a dengue outbreak in Key West, Florida, during 2009-2010, authorities, considered conducting the first US release of male Aedes aegypti mosquitoes genetically modified to prevent reproduction. Despite outreach and media attention, only half of the community was aware of the proposal; half of those were supportive. Novel public health strategies require community engagement.

Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials.

PubMed

Mitra, Sumita B; Oxman, Joe D; Falsafi, Afshin; Ton, Tiffany T

2011-12-01

To compare the long-term fluoride release kinetics of a novel nano-filled two-paste resin-modified glass-ionomer (RMGI), Ketac Nano (KN) with that of two powder-liquid resin-modified glass-ionomers, Fuji II LC (FLC) and Vitremer (VT) and one conventional glass-ionomer, Fuji IX (FIX). Fluoride release was measured in vitro using ion-selective electrodes. Kinetic analysis was done using regression analysis and compared with existing models for GIs and compomers. In a separate experiment the samples of KN and two conventional glass-ionomers, FIX and Ketac Molar (KM) were subjected to a treatment with external fluoride source (Oral-B Neutra-Foam) after 3 months of fluoride release and the recharge behavior studied for an additional 7-day period. The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P < 0.05. All four materials, including KN, showed a burst of fluoride ions at shorter times (t) and an overall rate dependence on t1/2 typical for glass-ionomers. The coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.

Berry phase in controlled light propagation and storage

NASA Astrophysics Data System (ADS)

Raczyński, Andrzej; Zaremba, Jarosław; Zielińska-Raczyńska, Sylwia

2018-04-01

It is shown that during light storage in an atomic medium in the Λ configuration, with not only the amplitude of the control field but also its phase changing adiabatically, a photon gains a Berry (geometric) phase. In the case of the tripod configuration with two probe fields the Berry phase is replaced by a 2 ×2 matrix. The probe fields are shown to be superpositions of two modes, each of them being characterized not only by its own velocity but also by its own Berry phase. If after light storage photons are released backwards, the contributions of the two modes interfere and the distribution of the outgoing photons can be steered by changing the difference between the Berry phases of the modes, due to the choice of the control field at the storage and release stages. In particular, one can turn a single photon of one of the probe fields into a photon of the other field or essentially modify coherent states of the incoming pulses.

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC.

PubMed

Sankalia, Jolly M; Sankalia, Mayur G; Mashru, Rajashree C

2008-07-02

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics

NASA Astrophysics Data System (ADS)

Labay, C.; Buxadera-Palomero, J.; Avilés, M.; Canal, C.; Ginebra, M. P.

2016-08-01

Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. A significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As a main consequence of the plasma polymerisation, the release kinetics were successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 h delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.

ATP release from freshly isolated guinea-pig bladder urothelial cells: a quantification and study of the mechanisms involved.

PubMed

McLatchie, Linda M; Fry, Christopher H

2015-06-01

To quantify the amount of ATP released from freshly isolated bladder urothelial cells, study its control by intracellular and extracellular calcium and identify the pathways responsible for its release. Urothelial cells were isolated from male guinea-pig urinary bladders and stimulated to release ATP by imposition of drag forces by repeated pipetting. ATP was measured using a luciferin-luciferase assay and the effects of modifying internal and external calcium concentration and blockers of potential release pathways studied. Freshly isolated guinea-pig urothelial cells released ATP at a mean (sem) rate of 1.9 (0.1) pmoles/mm(2) cell membrane, corresponding to about 700 pmoles/g of tissue, and about half [49 (6)%, n = 9) of the available cell ATP. This release was reduced to a mean (sem) of 0.46 (0.08) pmoles/mm(2) (160 pmoles/g) with 1.8 mm external calcium, and was increased about two-fold by increasing intracellular calcium. The release from umbrella cells was not significantly different from a mixed intermediate and basal cell population, suggesting that all three groups of cells release a similar amount of ATP per unit area. ATP release was reduced by ≈ 50% by agents that block pannexin and connexin hemichannels. It is suggested that the remainder may involve vesicular release. A significant fraction of cellular ATP is released from isolated urothelial cells by imposing drag forces that cause minimal loss of cell viability. This release involves multiple release pathways, including hemichannels and vesicular release. © 2014 The Authors BJU International © 2014 BJU International.

Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier.

PubMed

Kulkarni, Giriraj T; Sethi, Nitin; Awasthi, Rajendra; Pawar, Vivek Kumar; Pahuja, Vineet

2016-01-01

Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

Engineering dextran-based scaffolds for drug delivery and tissue repair

PubMed Central

Sun, Guoming; Mao, Jeremy J

2015-01-01

Owing to its chemically reactive hydroxyl groups, dextran can be modified with different functional groups to form spherical, tubular and 3D network structures. The development of novel functional scaffolds for efficient controlled release and tissue regeneration has been a major research interest, and offers promising therapeutics for many diseases. Dextran-based scaffolds are naturally biodegradable and can serve as bioactive carriers for many protein biomolecules. The reconstruction of the in vitro microenvironment with proper signaling cues for large-scale tissue regenerative scaffolds has yet to be fully developed, and remains a significant challenge in regenerative medicine. This paper will describe recent advances in dextran-based polymers and scaffolds for controlled release and tissue engineering. Special attention is given to the development of dextran-based hydrogels that are precisely manipulated with desired structural properties and encapsulated with defined angiogenic growth factors for therapeutic neovascularization, as well as their potential for wound repair. PMID:23210716

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

PubMed

Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

2018-02-01

The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

Orbital Injection of the SEDSAT Satellite: Tethered Systems Dynamics and Flight Data Analysis

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico C.; Gullahorn, Gordon E.; Cosmo, Mario L.; Ruiz, Manuel; Pelaez, Jesus

1996-01-01

This report deals with the following topics which are all related to the orbital injection of the SEDSAT satellite: Dynamics and Stability of Tether Oscillations after the First Cut. The dynamics of the tether after the first cut (i.e., without the Shuttle attached to it) is investigated. The tether oscillations with the free end are analyzed in order to assess the stability of the rectilinear configuration in between the two tether cuts; analysis of Unstable Modes. The unstable modes that appear for high libration angles are further investigated in order to determine their occurrences and the possible transition from bound librations to rotations; Orbital Release Strategies for SEDSAT. A parametric analysis of the orbital decay rate of the SEDSAT satellite after the two tether cuts has been carried out as a function of the following free parameters: libration amplitude at the end of deployment, deviation angle from LV at the first cut, and orbital anomaly at the second cut. The values of these parameters that provide a minimum orbital decay rate of the satellite (after the two cuts) have been computed; and Dynamics and Control of SEDSAT. The deployment control law has been modified to cope with the new ejection velocity of the satellite from the Shuttle cargo bay. New reference profiles have been derived as well as new control parameters. Timing errors at the satellite release as a function of the variations of the initial conditions and the tension model parameters have been estimated for the modified control law.

Biocompatible, smooth, plasma-treated nickel-titanium surface--an adequate platform for cell growth.

PubMed

Chrzanowski, W; Szade, J; Hart, A D; Knowles, J C; Dalby, M J

2012-02-01

High nickel content is believed to reduce the number of biomedical applications of nickel-titanium alloy due to the reported toxicity of nickel. The reduction in nickel release and minimized exposure of the cell to nickel can optimize the biocompatibility of the alloy and increase its use in the application where its shape memory effects and pseudoelasticity are particularly useful, e.g., spinal implants. Many treatments have been tried to improve the biocompatibility of Ni-Ti, and results suggest that a native, smooth surface could provide sufficient tolerance, biologically. We hypothesized that the native surface of nickel-titanium supports cell differentiation and insures good biocompatibility. Three types of surface modifications were investigated: thermal oxidation, alkali treatment, and plasma sputtering, and compared with smooth, ground surface. Thermal oxidation caused a drop in surface nickel content, while negligible chemistry changes were observed for plasma-modified samples when compared with control ground samples. In contrast, alkali treatment caused significant increase in surface nickel concentration and accelerated nickel release. Nickel release was also accelerated in thermally oxidized samples at 600 °C, while in other samples it remained at low level. Both thermal oxidation and alkali treatment increased the roughness of the surface, but mean roughness R(a) was significantly greater for the alkali-treated ones. Ground and plasma-modified samples had 'smooth' surfaces with R(a)=4 nm. Deformability tests showed that the adhesion of the surface layers on samples oxidized at 600 °C and alkali treatment samples was not sufficient; the layer delaminated upon deformation. It was observed that the cell cytoskeletons on the samples with a high nickel content or release were less developed, suggesting some negative effects of nickel on cell growth. These effects were observed primarily during initial cell contact with the surface. The most favorable cell responses were observed for ground and plasma-sputtered surfaces. These studies indicated that smooth, plasma-modified surfaces provide sufficient properties for cells to grow. © The Author(s), 2011.

Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

PubMed Central

Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

2014-01-01

Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

Effects of polyvinylpyrrolidone both as a binder and pore-former on the release of sparingly water-soluble topiramate from ethylcellulose coated pellets.

PubMed

Yang, Meiyan; Xie, Si; Li, Qiu; Wang, Yuli; Chang, Xinyi; Shan, Li; Sun, Lei; Huang, Xiaoli; Gao, Chunsheng

2014-04-25

Delivering sparingly water-soluble drugs from ethylcellulose (EC) coated pellets with a controlled-release pattern remains challenging. In the present study, hydrophilic polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former in EC coated pellets to deliver sparingly water-soluble topiramate, and the key factors that influenced drug release were identified. When the binder PVP content in drug layers below 20% w/w was decreased, the physical state of topiramate changed from amorphous to crystalline, making much difference to drug solubility and dissolution rates while modifying the drug release profile from first-order to zero-order. In addition, without PVP in drug layering solution, drug layered particles were less sticky during layering process, thus leading to a shorter process and higher loading efficiency. Furthermore, PVP level as a pore-former in EC coating layers mainly governed drug release from the coated pellets with the sensitivity ranging from 23% to 29%. PVP leaching rate and water permeability from EC/PVP film increased with the PVP level, which was perfectly correlated with drug release rate. Additionally, drug release from this formulation was independent of pH of release media or of the paddle mixing speed, but inversely proportional to the osmolality of release media above the physiological range. Copyright © 2014. Published by Elsevier B.V.

Spray drying of silica microparticles for sustained release application with a new sol-gel precursor.

PubMed

Wang, Bifeng; Friess, Wolfgang

2017-10-30

A new precursor, tetrakis(2-methoxyethyl) orthosilicate (TMEOS) was used to fabricate microparticles for sustained release application, specifically for biopharmaceuticals, by spray drying. The advantages of TMEOS over the currently applied precursors are its water solubility and hydrolysis at moderate pH without the need of organic solvents or catalyzers. Thus a detrimental effect on biomolecular drug is avoided. By generating spray-dried silica particles encapsulating the high molecular weight model compound FITC-dextran 150 via the nano spray dryer Büchi-90, we demonstrated how formulation parameters affect and enable control of drug release properties. The implemented strategies to regulate release included incorporating different quantities of dextrans with varying molecular weight as well as adjusting the pH of the precursor solution to modify the internal microstructures. The addition of dextran significantly altered the released amount, while the release became faster with increasing dextran molecular weight. A sustained release over 35days could be achieved with addition of 60 kD dextran. The rate of FITC-Dextran 150 release from the dextran 60 containing particles decreased with higher precursor solution pH. In conclusion, the new precursor TMEOS presents a promising alternative sol-gel technology based carrier material for sustained release application of high molecular weight biopharmaceutical drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

PubMed Central

Phaechamud, T.; Choncheewa, C.

2015-01-01

The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release. PMID:25767320

PLGA/Ag nanocomposites: in vitro degradation study and silver ion release.

PubMed

Fortunati, E; Latterini, L; Rinaldi, S; Kenny, J M; Armentano, I

2011-12-01

New nanocomposite films based on a biodegradable poly (DL-Lactide-co-Glycolide) copolymer (PLGA) and different concentration of silver nanoparticles (Ag) were developed by solvent casting. In vitro degradation studies of PLGA/Ag nanocomposites were conducted under physiological conditions, over a 5 week period, and compared to the behaviour of the neat polymer. Furthermore the silver ions (Ag(+)) release upon degradation was monitored to obtain information on the properties of the nanocomposites during the incubation. The obtained results suggest that the PLGA film morphology can be modified introducing a small percentage of silver nanoparticles that do not affect the degradation mechanism of PLGA polymer in the nanocomposite. However results clearly evinced the stabilizing effect of the Ag nanoparticles in the PLGA polymer and the mineralization process induced by the combined effect of silver and nanocomposite surface topography. The Ag(+) release can be controlled by the polymer degradation processes, evidencing a prolonged antibacterial effect.

Controlled-release biodegradable nanoparticles: From preparation to vaginal applications.

PubMed

Martínez-Pérez, Beatriz; Quintanar-Guerrero, David; Tapia-Tapia, Melina; Cisneros-Tamayo, Ricardo; Zambrano-Zaragoza, María L; Alcalá-Alcalá, Sergio; Mendoza-Muñoz, Néstor; Piñón-Segundo, Elizabeth

2018-03-30

This study aimed to prepare poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with chitosan (CTS) surface modification to be used as a vaginal delivery system for antimycotic drugs. Clotrimazole was encapsulated with entrapment efficiencies of 86.1 and 68.9% into Clotrimazole-PLGA-NPs (CLT-PLGA-NPs) and PLGA-NPs with CTS-modified surface (CLT-PLGA-CTS-NPs), respectively. The later NPs exhibited a larger size and higher positive zeta potential (Z potential) in comparison to unmodified NPs. In vitro release kinetic studies indicated that Clotrimazole was released in percentages of >98% from both nanoparticulate systems after 18days. Antifungal activity and mucoadhesive properties of NPs were enhanced when CTS was added onto the surface. In summary, these results suggested that Clotrimazole loaded into PLGA-CTS-NPs has great potential for vaginal applications in treating vaginal infections generated by Candida albicans. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of native and modified banana starch nanoparticles as vehicles for curcumin.

PubMed

Acevedo-Guevara, Leonardo; Nieto-Suaza, Leonardo; Sanchez, Leidy T; Pinzon, Magda I; Villa, Cristian C

2018-05-01

In recent years, starch nanoparticles have been of great interest for drug delivery due to their relatively easy synthesis, biocompatibility, and vast amount of botanical sources. Native and acetylated starch obtained from green bananas were used for synthesis of curcumin-loaded starch nanoparticles. Mean particle size, encapsulation efficiency, and curcumin release in simulated gastric and intestinal fluids were studied. Both nanosystems showed sizes lower than 250 nm and encapsulation efficiency above 80%, with acetylated banana starch nanoparticles having the capacity to encapsulate more curcumin molecules. Both FTIR and XRD analyses showed that starch acetylation allows stronger hydrogen bond interaction between curcumin and the starch matrix, thus, higher encapsulation efficiency. Finally, curcumin release studies showed that acetylated banana starch nanoparticles allowed more controlled release, probably due to their stronger hydrogen bond interaction with curcumin. Copyright © 2018. Published by Elsevier B.V.

Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

PubMed

Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

2016-02-08

This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

Investigation on influence of Wurster coating process parameters for the development of delayed release minitablets of Naproxen.

PubMed

Shah, Neha; Mehta, Tejal; Aware, Rahul; Shetty, Vasant

2017-12-01

The present work aims at studying process parameters affecting coating of minitablets (3 mm in diameter) through Wurster coating process. Minitablets of Naproxen with high drug loading were manufactured using 3 mm multi-tip punches. The release profile of core pellets (published) and minitablets was compared with that of marketed formulation. The core formulation of minitablets was found to show similarity in dissolution profile with marketed formulation and hence was further carried forward for functional coating over it. Wurster processing was implemented to pursue functional coating over core formulation. Different process parameters were screened and control strategy was applied for factors significantly affecting the process. Modified Plackett Burman Design was applied for studying important factors. Based on the significant factors and minimum level of coating required for functionalization, optimized process was executed. Final coated batch was evaluated for coating thickness, surface morphology, and drug release study.

A detailed view of microparticle formation by in-process monitoring of the glass transition temperature.

PubMed

Vay, Kerstin; Frieß, Wolfgang; Scheler, Stefan

2012-06-01

Biodegradable poly(D,L-lactide-co-glycolide) microspheres were prepared by a well-controlled emulsion solvent extraction/evaporation process. The objective of this study was to investigate how drug release can be modified by changing the morphology of the polymer matrix. The matrix structure was controlled by the preparation temperature which was varied between 10 and 35 °C, thus changing the 4 weeks release pattern from almost linear kinetics to a sigmoidal profile with a distinct lag phase and furthermore decreasing the encapsulation efficiency. By monitoring the glass transition temperature during the extraction process, it was shown that the preparation temperature determines the particle morphology by influencing the time span in which the polymer chains were mobile and flexible during the extraction process. Further factors determining drug release were found to be the molecular weight of the polymer and the rate of solvent removal. The latter, however, has also influence on the encapsulation efficiency with slow removal causing a higher drug loss. A secondary modification of the outer particle structure could be achieved by ethanolic post-treatment of the particles, which caused an extension of the lag phase and subsequently an accelerated drug release. Copyright © 2012. Published by Elsevier B.V.

Awareness and Support of Release of Genetically Modified “Sterile” Mosquitoes, Key West, Florida, USA

PubMed Central

Haenchen, Steven; Dickinson, Katherine; Doyle, Michael S.; Walker, Kathleen; Monaghan, Andrew J.; Hayden, Mary H.

2015-01-01

After a dengue outbreak in Key West, Florida, during 2009–2010, authorities, considered conducting the first US release of male Aedes aegypti mosquitoes genetically modified to prevent reproduction. Despite outreach and media attention, only half of the community was aware of the proposal; half of those were supportive. Novel public health strategies require community engagement. PMID:25625795

Central l-proline attenuates stress-induced dopamine and serotonin metabolism in the chick forebrain.

PubMed

Hamasu, Kousuke; Shigemi, Kazutaka; Kabuki, Yusuke; Tomonaga, Shozo; Denbow, D Michael; Furuse, Mitsuhiro

2009-08-21

Using microdialysis, we investigated the effect of l-proline on monoamine release in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) of freely moving and restricted chicks. A 30 min handling-stress resulted in a significant increase in extracellular homovallinic acid (HVA), a dopamine metabolite, and 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the MNH. l-Proline, perfused through the microdialysis probe into the MNH during the stressed condition, significantly attenuated the average dialysate concentration of HVA produced by handling-stress. Handling-stress resulted in a significant increase in 5-HIAA levels in the control group, which were attenuated by profusion with l-proline. l-Proline did not significantly modify basal concentrations of HVA or 5-HIAA in the MNH during control conditions. These results show that perfusion of l-proline modified the turnover/metabolism of dopamine and serotonin in the MNH caused by handling-stress.

Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

PubMed

Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

2012-01-17

The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

One-step grafting of temperature-and pH-sensitive (N-vinylcaprolactam-co-4-vinylpyridine) onto silicone rubber for drug delivery

PubMed Central

Pino-Ramos, Victor H.; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

2017-01-01

Abstract A one-step method was implemented to graft N-vinylcaprolactam (NVCL) and 4-vinylpyridine (4VP) onto silicone rubber (SR) films using gamma radiation in order to endow the silicone surface with temperature- and pH-responsiveness, and give it the ability to host and release diclofenac in a controlled manner and thus prevent bacterial adhesion. The effects of radiation conditions (e.g., dose and monomers concentration) on the grafting percentage were evaluated, and the modified films were characterized by means of FTIR-ATR, Raman spectroscopy, calorimetry techniques (DSC and TGA) and contact angle measurements. The films responsiveness to stimuli was evaluated by recording the swelling degree of pristine and modified SR in buffer solutions (critical pH point) and as a function of changes in temperature (Upper Critical Solution Temperature, UCST). The graft copolymers of SR-g-(NVCL-co-4VP) showed good cytocompatibility against fibroblast cells for prolonged times, could host diclofenac and release it in a sustained manner for up to 24 h, and exhibited bacteriostatic activity when challenged against Escherichia coli. PMID:29491777

The Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide.

PubMed

Clemens, Kristin K; McArthur, Eric; Dixon, Stephanie N; Fleet, Jamie L; Hramiak, Irene; Garg, Amit X

2015-08-01

The risk for hypoglycemia when taking glyburide compared with modified-release gliclazide remains to be established in older adults in routine care. We investigated the risk of a hospital encounter with hypoglycemia following a new prescription for glyburide compared with modified-release gliclazide. In 2 population-based matched retrospective cohort studies in Ontario, Canada, between 2002 and 2011, we examined older adults who were newly prescribed glyburide or gliclazide as monotherapy or in the presence of metformin. Our primary outcome was a hospital encounter with hypoglycemia assessed within 90 days. The baseline characteristics between matched groups were similar. Initiating glyburide vs. gliclazide as monotherapy was associated with a higher risk for a hospital encounter with hypoglycemia (69 patients of 4374 taking glyburide [1.58%] vs. 8 patients of 4374 taking gliclazide [0.18%], absolute risk increase 1.40% [95% CI 1.01% to 1.79%], number needed to harm 71 [55 to 99], odds ratio 8.63 [95% CI 4.15 to 17.93], p<0.0001). Similar findings were noted when glyburide vs. gliclazide was initiated in the presence of metformin (110 patients of 8038 taking glyburide [1.37%] vs. 19 patients of 8038 taking gliclazide [0.24%], absolute risk increase 1.13% [95% CI 0.86% to 1.40%], number needed to harm 77 [71 to 116], odds ratio 6.06 [95% CI 3.68 to 9.97], p<0.0001). Glyburide was associated with a higher risk for hypoglycemia than modified-release gliclazide. The results of our studies may help to convince healthcare professionals who use glyburide to consider modified-release gliclazide as a safer alternative. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Impact of Corrections to the Spallings Volume Calculation on Waste Isolation Pilot Plant Performance Assessment

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

Kicker, Dwayne Curtis; Herrick, Courtney G; Zeitler, Todd

2015-11-01

The numerical code DRSPALL (from direct release spallings) is written to calculate the volume of Waste Isolation Pilot Plant solid waste subject to material failure and transport to the surface (i.e., spallings) as a result of a hypothetical future inadvertent drilling intrusion into the repository. An error in the implementation of the DRSPALL finite difference equations was discovered and documented in a software problem report in accordance with the quality assurance procedure for software requirements. This paper describes the corrections to DRSPALL and documents the impact of the new spallings data from the modified DRSPALL on previous performance assessment calculations.more » Updated performance assessments result in more simulations with spallings, which generally translates to an increase in spallings releases to the accessible environment. Total normalized radionuclide releases using the modified DRSPALL data were determined by forming the summation of releases across each potential release pathway, namely borehole cuttings and cavings releases, spallings releases, direct brine releases, and transport releases. Because spallings releases are not a major contributor to the total releases, the updated performance assessment calculations of overall mean complementary cumulative distribution functions for total releases are virtually unchanged. Therefore, the corrections to the spallings volume calculation did not impact Waste Isolation Pilot Plant performance assessment calculation results.« less

Preparation of core-shell CaCO3 capsules via Pickering emulsion templates.

PubMed

Wang, Xiaoli; Zhou, Weizheng; Cao, Jian; Liu, Weichang; Zhu, Shiping

2012-04-15

Micron size and food grade pristine CaCO(3) particles were used to stabilize an oil in water Pickering emulsion. The particles also acted as nucleation sites for the subsequent crystallization of CaCO(3) with the addition of CaCl(2) and CO(2) gas as precursors. After the controllable crystallization process, a dense CaCO(3) shell with a few microns in thickness was formed. The CaCO(3) shell was proven to be calcite without the presence of crystallization modifiers. The crystallization speed and the shell integrity were controlled by manipulating the addition of CaCl(2) amount during the different crystallization stages; therefore, the homogeneous nucleation in the bulk was almost inhibited, and the heterogeneous nucleation at the oil-water interface on pristine CaCO(3) particles was the main contribution to the growth of the shell. The encapsulated limonene flavor in CaCO(3) capsules showed a prolonged release in neutral water at 85°C, while a burst release at pH 2 water as expected. The method is a simple and scalable process for creating inorganic core-shell capsules and can be used for producing food grade capsules for controlling the flavor release or masking undesirable taste in mouth. Copyright © 2012 Elsevier Inc. All rights reserved.

Modification of beta-cell response to different postprandial blood glucose concentrations by prandial repaglinide and combined acarbose/repaglinide application.

PubMed

Rosak, C; Hofmann, U; Paulwitz, O

2004-06-01

This study was designed to compare the effects of repaglinide plus acarbose combination treatment to repaglinide alone on postprandial glucose, serum insulin, C-peptide and proinsulin concentrations. A total of 40 patients with Type 2 diabetes (T2DM) (fasting blood glucose: 120-180 mg/dl; postprandial blood glucose: 140-240 mg/dl) were included in this single-centre, controlled, randomised, single-dose, cross-over study. On two consecutive days, patients either received 2 mg repaglinide 15 min before breakfast followed by 100 mg acarbose with breakfast or repaglinide alone. Two fasting (7.30 h, 8.00 h) and five postprandial blood samples (from 8.30 h to 12.00 h) were taken for blood glucose, serum insulin, C-peptide and proinsulin determination. Repaglinide plus acarbose treatment significantly reduced the mean increase in postprandial blood glucose levels (24.2+/-18.2 mg/dl) compared to repaglinide alone (51.1+/-29.0 mg/dl; p<0.001). Serum insulin, C-peptide and proinsulin levels [mean area under the curve (AUC7.30-12.00h)] were significantly lower than those observed with repaglinide monotherapy (e.g. insulin: 1089.2+/-604.5 hr x pmol/l and 1596.8+/-1080.6 hr x pmol/l, resp., p<0.001), suggesting that acarbose modifies the rapid insulin release induced by repaglinide. Prandial treatment with a combination of acarbose and repaglinide results in an additive glucose lowering effect and modified insulin secretion compared to repaglinide alone. Postprandial hyperglycaemia is not abolished by rapid stimulation of insulin release induced by repaglinide. Additional reduction of postprandial blood glucose by acarbose modifies the stimulation of insulin release.

Dual protection of wood surface treated with melamine-modified urea-formaldehyde resin mixed with ammonium polyphosphate against both fire and decay

Treesearch

Xing-xia Ma; Grant T. Kirker; Ming-liang Jiang; Yu-zhang Wu

2016-01-01

Surface coatings of melamine-modified urea-formaldehyde resins (MUFs) containing ammonium polyphosphate (APP) have been shown to significantly improve the fire retardancy of wood by prolonging the ignition time and reducing the heat release rate, total heat released, and mass loss rate. Dual protection of wood against both decay and fire has been proposed for remedial...

In vitro and in vivo evaluation of novel NGR-modified liposomes containing brucine.

PubMed

Li, Shu; Wang, Xi-Peng

2017-01-01

In this study, a novel NGR (Asn-Gly-Arg) peptide-modified liposomal brucine was prepared by using spray-drying method. The surface morphology of the liposomes, encapsulation efficiency and particle size were investigated. The data showed that the addition of NGR did not produce any significant influence on brucine liposomes in terms of particle size or zeta potential. In addition, after 3 months of storage, no dramatic change such as visible aggregation, drug content changes or precipitation in the appearance of NGR-brucine liposomes occurred. The in vitro release results indicated that the release of brucine from NGR liposomes was similar to that of liposomes, demonstrating that the NGR modification did not affect brucine release. The in vitro drug-release kinetic model of NGR-brucine liposomes fitted well with the Weibull's equation. In vivo, NGR-brucine liposomes could significantly extend the bioavailability of brucine; however, there was no significant difference observed in the pharmacokinetic parameters between liposomes and NGR liposomes after intravenous administration. Antitumor activity results showed that NGR-modified liposomes exhibited less toxicity and much higher efficacy in HepG2-bearing mice compared with non-modified liposomes. The enhanced antitumor activity might have occurred because brucine was specifically recognized by NGR receptor on the surface of tumor cells, which enhanced the intracellular uptake of drugs.

Development of Wax-Incorporated Emulsion Gel Beads for the Encapsulation and Intragastric Floating Delivery of the Active Antioxidant from Tamarindus indica L.

PubMed

Soradech, Sitthiphong; Petchtubtim, Intira; Thongdon-A, Jeerayu; Muangman, Thanchanok

2016-03-22

In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, TSCH95 and TSCH. All extracts exhibited high potential for superoxide anion scavenging activity over the IC50 range < 5-11 µg/mL and had no toxic effects on normal cells, however, the water extract (TSCH) was the most effective due to its free radical scavenging activity and toxicity in mitochondrial membranes of cancer cells. Next a study was designed to develop a new formulation for encapsulation and intragastric floating delivery of tamarind seed extract (TSCH) using wax-incorporated emulsion gel beads, which were prepared using a modified ionotropic gelation technique. Tamarind seed extract at 1% (w/w) was used as the active ingredient in all formulations. The effect of the types and amounts of wax on the encapsulation efficiency and percentage of the active release of alginate gel beads was also investigated. The results demonstrated that the incorporation of both waxes into the gel beads had an effect on the percentage of encapsulation efficiency (%) and the percentage of the active ingredient release. Furthermore, the addition of water insoluble waxes (carnauba and bee wax) significantly retarded the release of the active ingredient. The addition of both waxes had a slight effect on drug release behavior. Nevertheless, the increase in incorporated waxes in all formulations could sustain the percentage of active ingredient release. In conclusion, wax-incorporated emulsion gel beads using a modified ionotropic gelation technique could be applied for the intragastric floating delivery and controlled release of functional food and nutraceutical products for their antioxidant and anticancer capacity.

Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin β2 on Monocytes via NADPH Oxidase.

PubMed

Li, Ru; Klockenbusch, Cordula; Lin, Liwen; Jiang, Honghui; Lin, Shujun; Kast, Juergen

2016-12-02

Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation. To gain a better understanding of the redox regulation of monocytes in atherosclerosis, we have now altered the modified biotin switch to selectively quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation. Using arsenite as reducing agent in the modified biotin switch assay, we were able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were identified. Bioinformatics analysis of the quantified sulfenic acid sites highlighted the relevant, previously missed biological process of monocyte transendothelial migration, which included integrin β 2 . Flow cytometry validated the activation of LFA-1 (α L β 2 ) and Mac-1 (α M β 2 ), two subfamilies of integrin β 2 complexes, on human primary monocytes following platelet releasate treatment. The activation of LFA-1 was mediated by ROS from NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our results proved the modified biotin switch assay to be a powerful tool with the ability to reveal new regulatory mechanisms and identify new therapeutic targets.

Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

PubMed

Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

2016-12-01

In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

Electrospun Polymer Blend Nanofibers for Tunable Drug Delivery: The Role of Transformative Phase Separation on Controlling the Release Rate.

PubMed

Tipduangta, Pratchaya; Belton, Peter; Fábián, László; Wang, Li Ying; Tang, Huiru; Eddleston, Mark; Qi, Sheng

2016-01-04

Electrospun fibrous materials have a wide range of biomedical applications, many of them involving the use of polymers as matrices for incorporation of therapeutic agents. The use of polymer blends improves the tuneability of the physicochemical and mechanical properties of the drug loaded fibers. This also benefits the development of controlled drug release formulations, for which the release rate can be modified by altering the ratio of the polymers in the blend. However, to realize these benefits, a clear understanding of the phase behavior of the processed polymer blend is essential. This study reports an in depth investigation of the impact of the electrospinning process on the phase separation of a model partially miscible polymer blend, PVP K90 and HPMCAS, in comparison to other conventional solvent evaporation based processes including film casting and spin coating. The nanoscale stretching and ultrafast solvent removal of electrospinning lead to an enhanced apparent miscibility between the polymers, with the same blends showing micronscale phase separation when processed using film casting and spin coating. Nanoscale phase separation in electrospun blend fibers was confirmed in the dry state. Rapid, layered, macroscale phase separation of the two polymers occurred during the wetting of the fibers. This led to a biphasic drug release profile from the fibers, with a burst release from PVP-rich phases and a slower, more continuous release from HPMCAS-rich phases. It was noted that the model drug, paracetamol, had more favorable partitioning into the PVP-rich phase, which is likely to be a result of greater hydrogen bonding between PVP and paracetamol. This led to higher drug contents in the PVP-rich phases than the HPMCAS-rich phases. By alternating the proportions of the PVP and HPMCAS, the drug release rate can be modulated.

Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP.

PubMed

Centeno, José M; Miranda-Gómez, Luis; López-Morales, Mikahela A; Jover-Mengual, Teresa; Burguete, María C; Marrachelli, Vannina G; Castelló-Ruiz, María; Aliena-Valero, Alicia; Alborch, Enrique; Miranda, Francisco J

2018-05-01

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A 2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A 2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of K ATP and endothelial IK Ca channels.

Screening of anionic-modified polymers in terms of stability, disintegration, and swelling behavior.

PubMed

Laffleur, Flavia; Ijaz, Muhammad; Menzel, Claudia

2017-11-01

This study aimed to screen the stability, disintegration, and swelling behavior of chemically modified anionic polymers. Investigated polymers were well-known and widely used staples of the pharmaceutical and medical field, namely, alginate (AL), carboxymethyl cellulose (CMC), polycarbophil (PC), and hyaluronic acid (HA). On the basis of amide bond formation between the carboxylic acid moieties of anionic polymers and the primary amino group of the modification ligand cysteine (CYS), the modified polymers were obtained. Unmodified polymers served as controls throughout all studies. With the Ellman's assay, modification degrees were determined of synthesized polymeric excipients. Stability assay in terms of erosion study at physiological conditions were performed. Moreover, water uptake of compressed polymeric discs were evaluated and further disintegration studies according to the USP were carried out to define the potential ranking. Results ranking figured out PCCYS > CMCCYS > HACYS > ALCYS in terms of water uptake capacity compared to respective controls. Cell viability assays on Caco-2 cell line as well as on RPMI 2650 (ATTC CCL30) proved modification not being harmful to those. Due to the results of this study, an intense screening of prominent anionic polymer derivate was performed in order to help the pharmaceutical research for the best choice of polymeric excipients for developments of controlled drug release systems.

RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.

PubMed

Chang, Minglu; Lu, Shanshan; Zhang, Fang; Zuo, Tiantian; Guan, Yuanyuan; Wei, Ting; Shao, Wei; Lin, Guimei

2015-05-01

Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions have been described as efficient systems for delivery of therapeutic molecules into tumor cells. The aim of this work was to develop a drug delivery system based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine-aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment. Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method and characterized in detail, including by particle size, polydispersity, zeta potential and drug encapsulation efficiency. In vitro studies using MCF-7, HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied through tumor section imaging of xenograft mouse models of MCF-7 24h after intravenous administration. The particle size of the non-coated or RGD modified PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher cytotoxicity and cellular uptake relative to non-coated ones. The results of the in vivo study showed that RGD-coated PLPs had higher fluorescence, which suggested a more efficient accumulation than normal PLPs in tumors. In conclusion, these results confirmed RGD-modified PLPs as a potential drug delivery system to achieve controlled release and tumor targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of dry heating and ionic gum on the physicochemical and release properties of starch from Dioscorea.

PubMed

Vashisht, Deepika; Pandey, Anima; Hermenean, Anca; Yáñez-Gascón, Maria Josefa; Pérez-Sánchez, Horacio; Kumar, K Jayaram

2017-02-01

To meet the ever increasing industrial demand for excipients with desirable properties, modified starch is regarded as an alternative to it. With this in mind, the present study focuses on the modification of starches of Dioscorea from Jharkhand (India) using dry heat treatment with and without ionic gum. Modified starches were prepared using sodium alginate (1% w/w). Native and modified starches were subjected to heat treatment at 130°C for 2h and 4h. The effect of heating and ionic gum on the properties of Dioscorea starch was investigated. The amylose content, water holding capacity, micromeritic properties, swelling power, solubility and morphology of starches were evaluated. Dry heat treatment of starches without gum showed an increment in water-holding capacity after two-hours heating, but no such increment was found after four-hours heating. Oil binding capacity of starches modified with gum varied from 62% to 78%. Strongest effect of heat treatment occurred on the morphology of starches and thereby modified starches showed distorted surface morphology. Amylose content (21.09-21.89%) found to be decreased with the addition of gum which lead to decrease in paste clarity. Starches heated with gum at high-temperature resulted in restrict swelling and slight increase in solubility. Micromeritic properties of the modified starches showed the good flow properties. Further, the modified starches were investigated for in-vitro release studies and that the thermally modified derivatives can be a good prospect in slow release formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Food emulsions as delivery systems for flavor compounds: A review.

PubMed

Mao, Like; Roos, Yrjö H; Biliaderis, Costas G; Miao, Song

2017-10-13

Food flavor is an important attribute of quality food, and it largely determines consumer food preference. Many food products exist as emulsions or experience emulsification during processing, and therefore, a good understanding of flavor release from emulsions is essential to design food with desirable flavor characteristics. Emulsions are biphasic systems, where flavor compounds are partitioning into different phases, and the releases can be modulated through different ways. Emulsion ingredients, such as oils, emulsifiers, thickening agents, can interact with flavor compounds, thus modifying the thermodynamic behavior of flavor compounds. Emulsion structures, including droplet size and size distribution, viscosity, interface thickness, etc., can influence flavor component partition and their diffusion in the emulsions, resulting in different release kinetics. When emulsions are consumed in the mouth, both emulsion ingredients and structures undergo significant changes, resulting in different flavor perception. Special design of emulsion structures in the water phase, oil phase, and interface provides emulsions with great potential as delivery systems to control flavor release in wider applications. This review provides an overview of the current understanding of flavor release from emulsions, and how emulsions can behave as delivery systems for flavor compounds to better design novel food products with enhanced sensorial and nutritional attributes.

Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

PubMed

Dube, T S; Ranpise, N S; Ranade, A N

2014-01-01

The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

Recent innovations in edible and/or biodegradable packaging materials.

PubMed

Guilbert, S; Cuq, B; Gontard, N

1997-01-01

Certain newly discovered characteristics of natural biopolymers should make them a choice material to be used for different types of wrappings and films. Edible and/or biodegradable packagings produced from agricultural origin macromolecules provide a supplementary and sometimes essential means to control physiological, microbiological, and physicochemical changes in food products. This is accomplished (i) by controlling mass transfers between food product and ambient atmosphere or between components in heterogeneous food product, and (iii) by modifying and controlling food surface conditions (pH, level of specific functional agents, slow release of flavour compounds), it should be stressed that the material characteristics (polysaccharide, protein, or lipid, plasticized or not, chemically modified or not, used alone or in combination) and the fabrication procedures (casting of a film-forming solution, thermoforming) must be adapted to each specific food product and usage condition (relative humidity, temperature). Some potential uses of these materials (e.g. wrapping of various fabricated foods; protection of fruits and vegetables by control of maturation; protection of meat and fish; control of internal moisture transfer in pizzas), which are hinged on film properties (e.g. organoleptic, mechanical, gas and solute barrier) are described with examples.

Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

PubMed

Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

2004-12-01

Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

Transgenic Mosquitoes - Fact or Fiction?

PubMed

Wilke, André B B; Beier, John C; Benelli, Giovanni

2018-06-01

Technologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modified Composite Materials Workshop

NASA Technical Reports Server (NTRS)

Dicus, D. L. (Compiler)

1978-01-01

The reduction or elimination of the hazard which results from accidental release of graphite fibers from composite materials was studied at a workshop. At the workshop, groups were organized to consider six topics: epoxy modifications, epoxy replacement, fiber modifications, fiber coatings and new fibers, hybrids, and fiber release testing. Because of the time required to develop a new material and acquire a design data base, most of the workers concluded that a modified composite material would require about four to five years of development and testing before it could be applied to aircraft structures. The hybrid working group considered that some hybrid composites which reduce the risk of accidental fiber release might be put into service over the near term. The fiber release testing working group recommended a coordinated effort to define a suitable laboratory test.

Photoresponsive Release from Azobenzene-Modified Single Cubic Crystal NaCl/Silica Particles

DOE PAGES

Jiang, Xingmao; Liu, Nanguo; Assink, Roger A.; ...

2011-01-01

Azobenzene ligands were uniformly anchored to the pore surfaces of nanoporous silica particles with single crystal NaCl using 4-(3-triethoxysilylpropylureido)azobenzene (TSUA). The functionalization delayed the release of NaCl significantly. The modified particles demonstrated a photocontrolled release by trans/cis isomerization of azobenzene moieties. The addition of amphiphilic solvents, propylene glycol (PG), propylene glycol propyl ether (PGPE), and dipropylene glycol propyl ether (DPGPE) delayed the release in water, although the wetting behavior was improved and the delay is the most for the block molecules with the longest carbon chain. The speedup by UV irradiation suggests a strong dependence of diffusion on the switchablemore » pore size. TGA, XRD, FTIR, and NMR techniques were used to characterize the structures.« less

Multifunctional silk-heparin biomaterials for vascular tissue engineering applications

PubMed Central

Seib, F. Philipp; Herklotz, Manuela; Burke, Kelly A.; Maitz, Manfred F.; Werner, Carsten; Kaplan, David L.

2013-01-01

Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications. PMID:24099708

Drug-loaded poly (ε-caprolactone)/Fe3O4 composite microspheres for magnetic resonance imaging and controlled drug delivery

NASA Astrophysics Data System (ADS)

Wang, Guangshuo; Zhao, Dexing; Li, Nannan; Wang, Xuehan; Ma, Yingying

2018-06-01

In this study, poly (ε-caprolactone) (PCL) microspheres loading magnetic Fe3O4 nanoparticles and anti-cancer drug of doxorubicin hydrochloride (DOX) were successfully prepared by a modified solvent-evaporation method. The obtained magnetic composite microspheres exhibited dual features of magnetic resonance imaging and controlled drug delivery. The morphology, structure, thermal behavior and magnetic properties of the drug-loaded magnetic microspheres were investigated in detail by SEM, XRD, DSC and SQUID. The obtained composite microspheres showed superparamagnetic behavior and T2-weighted enhancement effect. The drug loading, encapsulation efficiency, releasing behavior and in vitro cytotoxicity of the drug-loaded composite microspheres were systematically investigated. It was found that the values of drug loading and encapsulation efficiency were 36.7% and 25.8%, respectively. The composite microspheres were sensitive to pH and released in a sustained way, and both the release curves under various pH conditions (4.0 and 7.4) were well satisfied with the biphase kinetics function. In addition, the magnetic response of the drug-loaded microspheres was studied and the results showed that the composite microspheres had a good magnetic stability and strong targeting ability.

Nanocomposite thin films for triggerable drug delivery.

PubMed

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Nano-engineered titanium for enhanced bone therapy

NASA Astrophysics Data System (ADS)

Gulati, Karan; Atkins, Gerald J.; Findlay, David M.; Losic, Dusan

2013-09-01

Current treatment of a number of orthopaedic conditions, for example fractures, bone infection, joint replacement and bone cancers, could be improved if mechanical support could be combined with drug delivery. A very challenging example is that of infection following joint replacement, which is very difficult to treat, can require multiple surgeries and compromises both the implant and the patient's wellbeing. An implant capable of providing appropriate biomechanics and releasing drugs/proteins locally might ensure improved healing of the traumatized bone. We propose fabrication of nanoengineered titanium bone implants using bioinert titanium wires in order to achieve this goal. Titanium in the form of flat foils and wires were modified by fabrication of titania nanotubes (TNTs), which are hollow self-ordered cylindrical tubes capable of accommodating substantial drug amounts and releasing them locally. To further control the release of drug to over a period of months, a thin layer of biodegradable polymer PLGA poly(lactic-coglycolic acid) was coated onto the drug loaded TNTs. This delayed release of drug and additionally the polymer enhanced bone cell adhesion and proliferation.

Labile conjugation of a hydrophilic drug to PLA oligomers to modify a drug delivery system: cephradin in a PLAGA matrix.

PubMed

Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramené, B

2000-01-01

The physical entrapment of a hydrophilic drug within degradable microspheres is generally difficult because of poor entrapment yield and/or fast release, depending on the microsphere fabrication method. In order to counter the effects of drug hydrophilicity, it is proposed to covalently attach the drug to lactic acid oligomers, with the aim of achieving temporary hydrophobization and slower release controlled by the separation of the drug from the degradable link within the polymer matrix. This strategy was tested on microspheres of the antibiotic cephradin. As the prodrug form, the entrapment of the drug was almost quantitative. The prodrug did degrade in an aqueous medium, modelling body fluids, but cleavage did not occur at the drug-oligomer junction and drug molecules bearing two lactyl residual units were released. When the prodrug is entrapped within a PLAGA matrix, no release was observed within the experimental time period. However, data suggest that conjugation via a bond more sensitive to hydrolysis than the main chain PLA ester bonds should make the system work as desired.

Catalytic Micromotors Moving Near Polyelectrolyte-Modified Substrates: The Roles of Surface Charges, Morphology, and Released Ions.

PubMed

Wei, Mengshi; Zhou, Chao; Tang, Jinyao; Wang, Wei

2018-01-24

Synthetic microswimmers, or micromotors, are finding potential uses in a wide range of applications, most of which involve boundaries. However, subtle yet important effects beyond physical confinement on the motor dynamics remain less understood. In this letter, glass substrates were functionalized with positively and negatively charged polyelectrolytes, and the dynamics of micromotors moving close to the modified surfaces was examined. Using acoustic levitation and numerical simulation, we reveal how the speed of a chemically propelled micromotor slows down significantly near a polyelectrolyte-modified surface by the combined effects of surface charges, surface morphology, and ions released from the films.

Overview of the current status of genetically modified plants in Europe as compared to the USA.

PubMed

Brandt, Peter

2003-07-01

Genetically modified crops have been tested in 1,726 experimental releases in the EU member states and in 7,815 experimental releases in the USA. The global commercial cultivation area of genetically modified crops is likely to reach 50 million hectares in 2001, however, the commercial production of genetically modified crops in the EU amounts to only a few thousand hectares and accounts for only some 0.03% of the world production. A significant gap exists between the more than fifty genetically modified crop species already permitted to be cultivated and to be placed on the market in the USA, Canada and other countries and the five genetically modified crop species permitted for the same use in the EU member states, which are still pending inclusion in the Common Catalogue of agricultural plant species. The further development of the "green gene technology" in the EU will be a matter of public acceptance and administrative legislation.

Chitinosans as tableting excipients for modified release delivery systems.

PubMed

Rege, P R; Shukla, D J; Block, L H

1999-04-20

The term 'chitinosans' embraces the spectrum of acetylated poly(N-glucosamines) ranging from chitin to chitosan. Chitinosans (I), at acidic pH, have protonated amines which can interact with oppositely charged drug ions and, thereby, modify drug release from drug delivery systems. Tablets were compressed from a physical mixture containing salicylic acid (II) as the model drug, I, and magnesium stearate. Five commercial I compounds, varying in degree of deacetylation and molecular weight, were selected. Tablets were compressed at 5000, 10 000, and 15 000 psig using a Carver and a single punch tablet press. The differential scanning calorimetry thermograms provided evidence of I-II interaction in the powder blend. Analysis of variance (ANOVA) indicated that the compression pressure did not significantly affect the crushing strength (CS) or the release profile of II from the I-matrix tablets (P?0.05). Furthermore, the ANOVA also indicated that the tablet press used during manufacture did not affect the above properties (P?0.05); however, the chitinosans significantly affected the CS as well as the release profile of II from I-matrix tablets (P<0.05). This study provides further evidence for the use of commercial I compounds as excipients for use in modified release drug delivery systems. Copyright.

Inorganic/Organic Hybrid Silica Nanoparticles as a Nitric Oxide Delivery Scaffold.

PubMed

Shin, Jae Ho; Schoenfisch, Mark H

2008-01-01

The preparation and characterization of nitric oxide (NO)-releasing silica particles formed following the synthesis of N -diazeniumdiolate-modified aminoalkoxysilanes are reported. Briefly, an aminoalkoxysilane solution was prepared by dissolving an appropriate amount of aminoalkoxysilane in a mixture of ethanol, methanol, and sodium methoxide (NaOMe) base. The silane solution was reacted with NO (5 atm) to form N -diazeniumdiolate NO donor moieties on the amino-alkoxysilanes. Tetraethoxy- or tetramethoxysilane (TEOS or TMOS) was then mixed with different ratios of N -diazeniumdiolate-modified aminoalkoxysilane (10 - 75 mol%, balance TEOS or TMOS). Finally, the silane mixture was added into ethanol in the presence of an ammonia catalyst to form NO donor silica nanoparticles via a sol-gel process. This synthetic approach allows for the preparation of NO delivery silica scaffolds with remarkably improved NO storage and release properties, surpassing all macromolecular NO donor systems reported to date with respect to NO payload (11.26μmol·mg -1 ), maximum NO release amount (357000 ppb·mg -1 ), NO release half-life (253 min), and NO release duration (101 h). The N -diazeniumdiolate-modified silane monomers and the resulting silica nanoparticles were characterized by 29 Si nuclear magnetic resonance (NMR) spectroscopy, UV-visible spectroscopy, chemiluminescence, atomic force microscopy (AFM), gas adsorption-desorption isotherms, and elemental analysis.

Optimal glucocorticoid therapy.

PubMed

Debono, Miguel; Ross, Richard J

2011-01-01

The rhythmic regulation of human physiology and behaviour is controlled by a central endogenous clock located in the suprachiasmatic nucleus. Most tissues have peripheral clocks that oscillate in time with this central clock. How the central time keeper controls peripheral clocks is not established, however there is evidence to suggest that the cortisol rhythm is one important secondary messenger. Loss of the endogenous cortisol rhythm is associated with sleep disturbance, depression, and metabolic abnormalities. In adrenal insufficiency, current glucocorticoid replacement regimens cannot replace the normal circadian rhythm of cortisol, and patients have an increased mortality and impaired quality of life. We propose that reproducing circadian cortisol levels may improve quality of life in patients with adrenal insufficiency and we have been investigating the impact of circadian hydrocortisone replacement. Using Chronocort, a modified release preparation of hydrocortisone, we have demonstrated that it is possible to simulate the overnight rise in cortisol release and, in preliminary studies in patients with congenital adrenal hyperplasia, control morning androgen levels. Future studies are now required to determine whether Chronocort can improve quality of life in patients with adrenal insufficiency. Copyright © 2011 S. Karger AG, Basel.

Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

PubMed

Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

2016-02-29

Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens.

PubMed

Oleinick, Arthur

2014-02-01

OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens. JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992-2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case-control study of EPA's Toxic Release Inventory 1988-2009 data compared carcinogen and non-carcinogens' releases. The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569-459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non-carcinogens. The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. © 2013 Wiley Periodicals, Inc.

The behaviour and recovery of juvenile lemon sharks Negaprion brevirostris in response to external accelerometer tag attachment.

PubMed

Bullock, R W; Guttridge, T L; Cowx, I G; Elliott, M; Gruber, S H

2015-12-01

Behavioural responses of lemon sharks Negaprion brevirostris to a fin-mounted tag package (CEFAS G6A tri-axial accelerometer with epoxied Sonotronics PT4 acoustic transmitter) were measured in a controlled captive environment (n = 10, total length, LT range 80-140 cm) and in free-ranging sharks upon release (n = 7, LT range 100-160 cm). No changes were detected in behaviour (i.e. swimming speed, tailbeat frequency, time spent resting and frequency of chafing) between control and tagged captive shark trials, suggesting that the tag package itself does not alter behaviour. In the free-ranging trials, an initial period of elevated swimming activity was found in all individuals (represented by overall dynamic body acceleration). Negaprion brevirostris, however, appeared to recover quickly, returning to a steady swimming state between 2 and 35 min after release. Post-release tracking found that all sharks swim immediately for the shoreline and remain within 100 m of shore for prolonged periods. Hence, although N. brevirostris are capable of quick adaptation to stressors and demonstrate rapid recovery in terms of activity, tracking data suggest that they may modify their spatial use patterns post release. This research is important in separating deviation in behaviour due to environmental stressors from artefacts caused by experimental techniques. © 2015 The Fisheries Society of the British Isles.

Development and agronomical validation of new fertilizer compositions of high bioavailability and reduced potential nutrient losses.

PubMed

Erro, Javier; Urrutia, Oscar; San Francisco, Sara; Garcia-Mina, Jose M

2007-09-19

To optimize the economical cost of each unit of fertilizer applied and to reduce the environmental contamination caused by nutrient losses, the development of highly efficient granulated fertilizers is of great importance. This study proposes a strategy that consists of developing specific fertilizers having nutrient release patterns that are dependent on plant activity in the rhizosphere. This type of fertilizer is named "rhizosphere-controlled fertilizer" (RCF fertilizer). This fertilizer is based on the introduction of an organomineral matrix composed of metal [Mg (Ca is also possible), Zn (Fe and other metals are also possible)]-humic phosphates. The presence of this matrix modifies the nutrient release pattern of the fertilizer. In this way there are two main nutrient fractions: (i) a water-soluble fraction or "starter" fraction and (ii) a "rhizosphere-controlled" fraction insoluble in water but soluble by the action of the rhizospheric acids released by plants and microorganisms. This study shows the chemical and structural characterization of the organomineral matrix, as well as its efficiency in slowing the nutrient release rate of the RCF fertilizer, principally with respect to P and N. It is demonstrated how these properties of the matrix were also reflected in the significant reduction in both ammonia volatilization and N leaching in a pot system consisting of wheat plants cultivated in a calcareous soil and fertilized with a RCF fertilizer.

Effect of alpha-adrenoceptor antagonists (phentolamine, nicergoline and prazosin) on reperfusion arrhythmias and noradrenaline release in perfused rat heart.

PubMed Central

Bralet, J.; Didier, J.; Moreau, D.; Opie, L. H.; Rochette, L.

1985-01-01

Rat isolated hearts were perfused through the left atrium with a modified Krebs-Henseleit solution or mounted on a Langendorff perfusion system. The hearts were prelabelled with [3H]-noradrenaline [( 3H]-NA) and the left main coronary artery was ligated for 10 min after which reperfusion followed. The liberation of [3H]-NA and the development of ventricular tachycardia and fibrillation were monitored throughout. During the occlusion period, ventricular arrhythmias did not occur and heart rate was not significantly altered in the control series. In contrast, reperfusion was followed by ventricular fibrillation and ventricular tachycardia in all the hearts in the control series (Langendorff or 'working' models). The alpha-adrenoceptor antagonists phentolamine (7.1 X 10(-6) M and 7.1 X 10(-5) M) and nicergoline (3.1 X 10(-6) M) diminished or prevented reperfusion arrhythmias. However, prazosin (5.2 X 10(-6) M) was not effective. The lower concentration of phentolamine did not alter the pattern of [3H]-NA release, whereas, high doses of phentolamine and nicergoline increased the release of [3H]-NA. Prazosin (5.2 X 10(-6) M) caused a very marked increase in release of [3H]-NA but was not antiarrhythmic. A 'membrane-stabilizing' effect seems the most appropriate explanation for these antiarrhythmic effects of alpha-antagonist agents. PMID:2858234

Fail-Safe Pressure Plug

NASA Technical Reports Server (NTRS)

Svejkovsky, Paul A.

1993-01-01

Protective plug resists slowly built-up pressure or automatically releases itself if pressure rises suddenly. Seals out moisture at pressures ranging from 50 micrometers of mercury to 200 pounds per square inch. Designed to seal throat of 38 Reaction Control Thrusters on Space Shuttle protecting internal components from corrosion. Plug conforms to contour of nozzle throat, where O-ring forms pressure seal. After plug inserted, cover attached by use of cover-fitting assembly. Modified versions useful in protecting engines, pumps, reaction vessels, and other industrial equipment during shipment and maintenance.

Prefrontal cortex, caloric restriction and stress during aging: studies on dopamine and acetylcholine release, BDNF and working memory.

PubMed

Del Arco, Alberto; Segovia, Gregorio; de Blas, Marta; Garrido, Pedro; Acuña-Castroviejo, Dario; Pamplona, Reinald; Mora, Francisco

2011-01-01

This study was designed to investigate whether long-term caloric restriction during the life span of the rat changes the effects of an acute mild stress on the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and on working memory performance. Spontaneous motor activity was also monitored and levels of BDNF measured in the prefrontal cortex, amygdala and hippocampus. Male Wistar rats (3 months of age) were housed during 3, 12, 21 and 27 months (6, 15, 24 and 30 months of age at the end of housing) in caloric restriction (CR; 40% food intake restriction) or control conditions. After behavioural testing, animals were further subdivided into two other groups. In one of the groups BDNF protein levels were determined. In the other group rats were implanted with guide cannulas into the PFC to perform microdialysis experiments. In CR rats the release of dopamine produced by handling stress did not differ from the response found in control rats of 6, 15 and 24 months of age. The release of acetylcholine was not changed at the ages of 6 and 15 months but reduced at the age of 24 months. Stress did not change dopamine or acetylcholine release in CR and control rats of 30 months of age. BDNF levels were increased in the hippocampus and amygdala, but not in the PFC, of 6 and 15 months CR rats. Spontaneous motor activity was increased in all groups of CR rats. Age, however, decreased motor activity in CR and control rats. Both experimental groups showed similar working memory performance in a delayed alternation task in basal conditions and after a situation of acute stress. These results suggest that CR does not modify the function of the PFC in response to an acute stress nor the changes found as a result of the normal process of aging. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

PubMed

Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

2002-01-01

Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with ADHD.

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

PubMed

Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

2002-01-01

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

Modeling of Fission Gas Release in UO2

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

MH Krohn

2006-01-23

A two-stage gas release model was examined to determine if it could provide a physically realistic and accurate model for fission gas release under Prometheus conditions. The single-stage Booth model [1], which is often used to calculate fission gas release, is considered to be oversimplified and not representative of the mechanisms that occur during fission gas release. Two-stage gas release models require saturation at the grain boundaries before gas is release, leading to a time delay in release of gases generated in the fuel. Two versions of a two-stage model developed by Forsberg and Massih [2] were implemented using Mathcadmore » [3]. The original Forsbers and Massih model [2] and a modified version of the Forsberg and Massih model that is used in a commercially available fuel performance code (FRAPCON-3) [4] were examined. After an examination of these models, it is apparent that without further development and validation neither of these models should be used to calculate fission gas release under Prometheus-type conditions. There is too much uncertainty in the input parameters used in the models. In addition. the data used to tune the modified Forsberg and Massih model (FRAPCON-3) was collected under commercial reactor conditions, which will have higher fission rates relative to Prometheus conditions [4].« less

Production of oleanolic acid glycosides by hairy root established cultures of Calendula officinalis L.

PubMed

Długosz, Marek; Wiktorowska, Ewa; Wiśniewska, Anita; Pączkowski, Cezary

2013-01-01

In order to initiate hairy root culture initiation cotyledons and hypocotyls of Calendula officinalis L. were infected with Agrobacterium rhizogenes strain ATCC 15834 or the same strain containing pCAMBIA 1381Z vector with β-glucuronidase reporter gene under control of promoter of NIK (Nematode Induced Kinase) gene. The efficiency of induction of hairy roots reached 33.8% for cotyledons and 66.6% for hypocotyls together for both transformation experiments. Finally, eight control and nine modified lines were established as a long-term culture. The hairy root cultures showed the ability to synthesize oleanolic acid mainly (97%) as glycosides; control lines contained it at the average 8.42 mg · g(-1) dry weight in tissue and 0.23 mg · dm(-3) in medium; modified lines: 4.59 mg · g(-1) for the tissue, and 0.48 mg · dm(-3) for the medium. Additionally lines showed high positive correlation between dry/fresh weight and oleanolic acid concentration in tissue. Using the Killiani mixture in acidic hydrolysis of oleanolic acid glycosides released free aglycones that were partially acetylated in such conditions.

The fabrication of well-interconnected polycaprolactone/hydroxyapatite composite scaffolds, enhancing the exposure of hydroxyapatite using the wire-network molding technique.

PubMed

Cho, Yong Sang; Hong, Myoung Wha; Jeong, Hoon-Jin; Lee, Seung-Jae; Kim, Young Yul; Cho, Young-Sam

2017-11-01

In this study, the fabrication method was proposed for the well-interconnected polycaprolactone/hydroxyapatite composite scaffold with exposed hydroxyapatite using modified WNM technique. To characterize well-interconnected scaffolds in terms of hydroxyapatite exposure, several assessments were performed as follows: morphology, mechanical property, wettability, calcium ion release, and cell response assessments. The results of these assessments were compared with those of control scaffolds which were fabricated by precision extruding deposition (PED) apparatus. The control PED scaffolds have interconnected pores with nonexposed hydroxyapatite. Consequently, cell attachment of proposed WNM scaffold was improved by increased hydrophilicity and surface roughness of scaffold surface resulting from the exposure of hydroxyapatite particles and fabrication process using powders. Moreover, cell proliferation and differentiation of WNM scaffold were increased, because the exposure of hydroxyapatite particles may enhance cell adhesion and calcium ion release. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2315-2325, 2017. © 2016 Wiley Periodicals, Inc.

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs.

PubMed

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P C; Cai, Yu

2017-05-27

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid-polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core-shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs', PNPs', and PLNs' structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system.

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs

PubMed Central

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P. C.; Cai, Yu

2017-01-01

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid–polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core–shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs’, PNPs’, and PLNs’ structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system. PMID:28554993

[Adsorption of aflatoxin on montmorillonite modified by low-molecular-weight humic acids].

PubMed

Yao, Jia-Jia; Kang, Fu-Xing; Gao, Yan-Zheng

2012-03-01

The adsorption of a typical biogenic toxin aflatoxin B1 on montmorillonite modified by low-molecular-weight humic acids (M(r) < 3 500) was investigated. The montmorillonite rapidly adsorbed the aflatoxin B1 until amounting to the maximal capacity, and then the adsorbed aflatoxin B1 slowly released into solution and reached the sorption equilibrium state after 12 h. The sorption isotherm of aflatoxin B1 by montmorillonite could be well described by Langmiur model, while the sorption isotherm by humic acid-modified montmorillonite was well fitted by using the Freundlich model. The modification of the montmorillonite with humic acids obviously enhanced its adsorption capacity for aflatoxin B1, and the amounts of aflatoxin adsorbed by modified montmorillonite were obviously higher than those by montmorillonite. The sorption enhancement by humic acid modification was attributed to (1) the enlarged adsorption sites which owed to the surface collapse of crystal layers induced by organic acids, and (2) the binding of aflatoxin with the humic acid sorbed on mineral surface. In addition, the adsorption amounts of aflatoxin by montmorillonite and modified montmorillonite increased with the increase of pH values in solution, and more significant enhancement was observed for the latter than the former, which attributed to the release of humic acids from the modified montmorillonite with the high pH values in solution. This indicates that increasing the pH values resulted in the enhanced hydrophilic property and the release of the organic acids presented in modified montmorillonite, and more sorption sites were available for aflatoxin on the modified montmorillonite. Results of this work would strengthen our understanding of the behavior and fate of biological contaminants in the environment.

Controlled, sustained release of proteins via an injectable, mineral-coated microsphere delivery vehicle

NASA Astrophysics Data System (ADS)

Franklin-Ford, Travelle

Hydroxyapatite interfaces have demonstrated strong protein binding and protein selection from a passing solution and can serve as a biocompatible carrier for controlled protein delivery. Hydroxyapatite is a major component of long bones and tooth enamel and is the most stable of all calcium phosphate isoforms in aqueous solutions at physiologic pH, providing a sensitive chromatographic mechanism for separating proteins. Here we describe an approach to create a synthetic hydroxyapatite coating through a biomimetic, heterogeneous nucleation from a modified simulated body fluid--supersaturated with calcium and phosphate ions on the surface of injectable polymer microspheres. We are able to bind and release bioactive growth factors into a variety of in vitro and in vivo conditions, demonstrating the functionality and advantage of the biomaterial. Creating a hydroxyapatite layer on the Poly(D,L-lactide-co-glycolide) (PLG) microsphere surface, avails the microsphere interior for another application that will not compete with protein binding and release. Encapsulating an imaging agent within the aqueous phase of the emulsion provides a visual reference for the injectable therapy upon microsphere fabrication. Another advantage of this system is that the mineral coating and subsequent protein binding is not compromised by the encapsulated imaging agent. This dual function delivery vehicle is not only advantageous for spatial tracking therapeutic applications, but also determining the longevity of the delivery vehicle once injected. In the broader sense, providing a mechanism to image and track our temporally controlled, sustained delivery system gives more evidence to support the effects of released protein on in vivo responses (bioactivity) and locate microspheres within different biological systems.

77 FR 7172 - Sequoyah National Wildlife Refuge, Sequoyah, Muskogee, and Haskell Counties, OK; Comprehensive...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

.... Scoping for the environmental assessment (EA) on use of specified genetically modified crops in... of genetically modified crops in association with the cooperative farming program was released on... assessment of using specified genetically modified crops into the CCP and determined that an environmental...

The effect of prime emulsion components as a function of equilibrium headspace concentration of soursop flavor compounds

PubMed Central

2014-01-01

Background Perceptions of food products start when flavor compounds are released from foods, transported and appropriate senses in the oral and nose are triggered. However, the long-term stability of flavor compounds in food product has been a major concern in the food industry due to the complex interactions between key food ingredients (e.g., polysaccharides and proteins). Hence, this study was conducted to formulate emulsion-based beverage using natural food emulsifiers and to understand the interactions between emulsion compositions and flavor compounds. Results The influences of modified starch (x 1 ), whey protein isolate (x 2 ), soursop flavor oil (x 3 ) and deionized water (x 4 ) on the equilibrium headspace concentration of soursop volatile flavor compounds were evaluated using a four-component with constrained extreme vertices mixture design. The results indicated that the equilibrium headspace concentration of soursop flavor compounds were significantly (p < 0.05) influenced by the matrix and structural compositions of the beverage emulsions. Interface formed using modified starch and whey protein isolate (WPI) proved to be capable of inhibiting the release of volatile flavor compounds from the oil to the aqueous phase. Modified starch could retard the overall flavor release through its hydrophobic interactions with volatile flavor compounds and viscosity enhancement effect. Excessive amount of modified starch was also shown to be detrimental to the stability of emulsion system. However, both modified starch and WPI showed to be a much more effective barrier in inhibiting the flavor release of flavor compounds when used as individual emulsifier than as a mixture. Conclusions Overall, the mixture design can be practical in elucidating the complex interactions between key food components and volatile flavor compounds in an emulsion system. These studies will be useful for the manufacturers for the formulation of an optimum beverage emulsion with desirable emulsion properties and desirable flavor release profile. PMID:24708894

A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and in vitro/vivo evaluation

PubMed Central

Chen, Jingde; Jiang, Hong; Wu, Yin; Li, Yandong; Gao, Yong

2015-01-01

In this study, oxaliplatin (OX) liposomes surface-modified with glycyrrhetinic acid (GA) were developed by the film-dispersion method. Their morphology, physical and chemical properties, and in vitro release performance were investigated. The transmission electron microscope (TEM) image showed that most liposomes were spherical particles with similar size and uniform dispersion. Both OX-liposomes and GA-OX-liposomes had an average size of 90 nm. They were negatively charged, with zeta potentials of −20.6 and −21.3 mV, respectively, and the entrapment efficiency values of both were higher than 94%. In vitro data showed that the application of liposomes could prolong the OX release. The relatively high correlation coefficient values obtained from analyzing the amount of drug released versus the square root of time depicted that release followed the Weibull model. No significant changes were observed after the addition of GA to the liposomes. In vivo, the relatively long time to reach the maximum plasma concentration of OX-liposomes suggested a sustained-release profile of liposomes, which was consistent with the results of the in vitro release study. The increased area under the curve and maximum plasma concentration of OX-liposomes and GA-OX-liposomes demonstrated an increased absorption. The drug concentration in tissues indicated that the GA-modified liposomes delivered OX mainly to liver after intravenous administration. In addition, no severe signs, such as appearance of epithelial necrosis or sloughing of epithelial cells, were detected in histology studies. PMID:25945038

Modification of Silicone Elastomer Surfaces with Zwitterionic Polymers: Short-Term Fouling Resistance and Triggered Biofouling Release.

PubMed

Shivapooja, Phanindhar; Yu, Qian; Orihuela, Beatriz; Mays, Robin; Rittschof, Daniel; Genzer, Jan; López, Gabriel P

2015-11-25

We present a method for dual-mode-management of biofouling by modifying surface of silicone elastomers with zwitterionic polymeric grafts. Poly(sulfobetaine methacrylate) was grafted from poly(vinylmethylsiloxane) elastomer substrates using thiol-ene click chemistry and surface-initiated, controlled radical polymerization. These surfaces exhibited both fouling resistance and triggered fouling-release functionality. The zwitterionic polymers exhibited fouling resistance over short-term (∼hours) exposure to bacteria and barnacle cyprids. The biofilms that eventually accumulated over prolonged-exposure (∼days) were easily detached by applying mechanical strain to the elastomer substrate. Such dual-functional surfaces may be useful in developing environmentally and biologically friendly coatings for biofouling management on marine, industrial, and biomedical equipment because they can obviate the use of toxic compounds.

PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.

PubMed

Chan, Juliana M; Zhang, Liangfang; Yuet, Kai P; Liao, Grace; Rhee, June-Wha; Langer, Robert; Farokhzad, Omid C

2009-03-01

Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.

Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.

PubMed

Marrachelli, Vannina G; Miranda, Francisco J; Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Jover-Mengual, Teresa; Pérez, Antonio M; Salom, Juan B; Torregrosa, Germán; Alborch, Enrique

2010-02-01

Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modify relaxations to testosterone neither in control nor in diabetic rabbits. In endothelium-denuded arteries indomethacin enhanced the relaxant action of testosterone, both in control and diabetic rabbits. In arteries from diabetic rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of thromboxane A(2) and prostacyclin were not significantly different from those observed in control rabbits. However, COX-2 expression was significantly lower in diabetic rabbits that in control rabbits. In nominally Ca(2+)-free medium, cumulative addition of CaCl2 (10(-5) to 3x10(-2)M) contracted previously depolarized arteries. Testosterone (10(-4)M) inhibited CaCl2 contractions of the renal artery both in control and diabetic rabbits. These results show that testosterone relaxes the renal artery both in control and diabetic rabbits. This relaxation is modulated by muscular thromboxane A(2), it is partially mediated by endothelial prostacyclin, and it involves the blocking of extracellular Ca2+ entry. Diabetes does not modify the mechanisms involved in the relaxant action of testosterone in the rabbit renal artery. Copyright 2009 Elsevier Ltd. All rights reserved.

A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery.

PubMed

Yehia, Soad A; Elshafeey, Ahmed H; Elsayed, Ibrahim

2012-06-01

One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1-24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.

Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.

PubMed

Sehgal, Rekha R; Roohani-Esfahani, S I; Zreiqat, Hala; Banerjee, Rinti

2017-04-01

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca 3 ZrSi 2 O 9 ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A bionanohybrid ZnAl-NADS ecological pesticide as a treatment for soft rot disease in potato (Solanum tuberosum L.).

PubMed

Morales-Irigoyen, Erika Elizabeth; de Las Mercedes Gómez-Y-Gómez, Yolanda; Flores-Moreno, Jorge Luis; Franco-Hernández, Marina Olivia

2017-09-18

Pectobacterium carotovorum (Pc) is a phytopathogenic strain that causes soft rot disease in potato (Solanum tuberosum L.), resulting in postharvest losses. Chemical control is effective for managing this disease, but overdoses cause adverse effects. Because farmers insist on using chemical agents for crop protection, it is necessary to develop more effective pesticides in which the active compound released can be regulated. In this context, we proposed the synthesis of ZnAl-NADS, in which nalidixic acid sodium salt (NADS) is linked to a ZnAl-NO 3 layered double hydroxide (LDH) host as a nanocarrier. XRD, FT-IR, and SEM analyses confirmed the successful intercalation of NADS into the interplanar LDH space. The drug release profile indicated that the maximum release was completed in 70 or 170 min for free NADS (alone) or for NADS released from ZnAl-NADS, respectively. This slow release was attributed to strong electrostatic interactions between the drug and the anion exchanger. A modulated release is preferable to the action of the bulk NADS, showing increased effectiveness and minimizing the amount of the chemical available to pollute the soil and the water. The fitting data from modified Freundlich and parabolic diffusion models explain the release behavior of the NADS, suggesting that the drug released from ZnAl-NADS bionanohybrid was carried out from the interlamellar sites, according to the ion exchange diffusion process also involving intraparticle diffusion (coeffect). ZnAl-NADS was tested in vitro against Escherichia coli (Ec) and Pc and exhibited bacteriostatic and biocidal effects at 0.025 and 0.075 mg mL -1 , respectively. ZnAl-NADS was also tested in vivo as an ecological pesticide for combating potato soft rot and was found to delay typical disease symptoms. In conclusion, ZnAl-NADS can potentially be used to control pests, infestation, and plant disease.

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Size-controlled fabrication of zein nano/microparticles by modified anti-solvent precipitation with/without sodium caseinate

PubMed Central

Li, Feng; Chen, Yan; Liu, Shubo; Qi, Jian; Wang, Weiying; Wang, Chenhua; Zhong, Ruiyue; Chen, Zhijun; Li, Xiaoming; Guan, Yuanzhou; Kong, Wei; Zhang, Yong

2017-01-01

Zein-based nano/microparticles have been demonstrated to be promising carrier systems for both the food industry and biomedical applications. However, the fabrication of size-controlled zein particles has been a challenging issue. In this study, a modified anti-solvent precipitation method was developed, and the effects of various factors, such as mixing method, solvent/anti-solvent ratio, temperature, zein concentrations and the presence of sodium caseinate (SC) on properties of zein particles were investigated. Evidence is presented that, among the previously mentioned factors, the mixing method, especially mixing rate, could be used as an effective parameter to control the size of zein particles without changing other parameters. Moreover, through fine-tuning the mixing rate together with zein concentration, particles with sizes ranging from nanometers to micrometers and low polydispersity index values could be easily obtained. Based on the size-controlled fabrication method, SC-coated zein nanoparticles could also be obtained in a size-controlled manner by incubation of the coating material with the already-formed zein particles. The resultant nanoparticles showed better performance in both drug loading and controlled release, compared with zein/SC hybrid nanoparticles fabricated by adding aqueous ethanol solution to SC solution. The possible mechanisms of the nanoprecipitation process and self-assembly formation of these nanoparticles are discussed. PMID:29184408

Size-controlled fabrication of zein nano/microparticles by modified anti-solvent precipitation with/without sodium caseinate.

PubMed

Li, Feng; Chen, Yan; Liu, Shubo; Qi, Jian; Wang, Weiying; Wang, Chenhua; Zhong, Ruiyue; Chen, Zhijun; Li, Xiaoming; Guan, Yuanzhou; Kong, Wei; Zhang, Yong

2017-01-01

Zein-based nano/microparticles have been demonstrated to be promising carrier systems for both the food industry and biomedical applications. However, the fabrication of size-controlled zein particles has been a challenging issue. In this study, a modified anti-solvent precipitation method was developed, and the effects of various factors, such as mixing method, solvent/anti-solvent ratio, temperature, zein concentrations and the presence of sodium caseinate (SC) on properties of zein particles were investigated. Evidence is presented that, among the previously mentioned factors, the mixing method, especially mixing rate, could be used as an effective parameter to control the size of zein particles without changing other parameters. Moreover, through fine-tuning the mixing rate together with zein concentration, particles with sizes ranging from nanometers to micrometers and low polydispersity index values could be easily obtained. Based on the size-controlled fabrication method, SC-coated zein nanoparticles could also be obtained in a size-controlled manner by incubation of the coating material with the already-formed zein particles. The resultant nanoparticles showed better performance in both drug loading and controlled release, compared with zein/SC hybrid nanoparticles fabricated by adding aqueous ethanol solution to SC solution. The possible mechanisms of the nanoprecipitation process and self-assembly formation of these nanoparticles are discussed.

Mussel-Inspired Protein Nanoparticles Containing Iron(III)-DOPA Complexes for pH-Responsive Drug Delivery.

PubMed

Kim, Bum Jin; Cheong, Hogyun; Hwang, Byeong Hee; Cha, Hyung Joon

2015-06-15

A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH-responsive drug release exploits the pH-dependent changes in the coordination stoichiometry of iron(III)-3,4-dihydroxyphenylalanine (DOPA) complexes, which play a major cross-linking role in mussel byssal threads. Doxorubicin-loaded polymeric NPs that are based on Fe(III)-DOPA complexation were thus synthesized with a DOPA-modified recombinant mussel adhesive protein through a co-electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the Fe(III)-DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that Fe(III)-DOPA complexation can be successfully utilized as a new design principle for pH-responsive NPs for diverse controlled drug-delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced synaptic transmission at the squid giant synapse by artificial seawater based on physically modified saline

PubMed Central

Choi, Soonwook; Yu, Eunah; Rabello, Guilherme; Merlo, Suelen; Zemmar, Ajmal; Walton, Kerry D.; Moreno, Herman; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

2014-01-01

Superfusion of the squid giant synapse with artificial seawater (ASW) based on isotonic saline containing oxygen nanobubbles (RNS60 ASW) generates an enhancement of synaptic transmission. This was determined by examining the postsynaptic response to single and repetitive presynaptic spike activation, spontaneous transmitter release, and presynaptic voltage clamp studies. In the presence of RNS60 ASW single presynaptic stimulation elicited larger postsynaptic potentials (PSP) and more robust recovery from high frequency stimulation than in control ASW. Analysis of postsynaptic noise revealed an increase in spontaneous transmitter release with modified noise kinetics in RNS60 ASW. Presynaptic voltage clamp demonstrated an increased EPSP, without an increase in presynaptic ICa++ amplitude during RNS60 ASW superfusion. Synaptic release enhancement reached stable maxima within 5–10 min of RNS60 ASW superfusion and was maintained for the entire recording time, up to 1 h. Electronmicroscopic morphometry indicated a decrease in synaptic vesicle density and the number at active zones with an increase in the number of clathrin-coated vesicles (CCV) and large endosome-like vesicles near junctional sites. Block of mitochondrial ATP synthesis by presynaptic injection of oligomycin reduced spontaneous release and prevented the synaptic noise increase seen in RNS60 ASW. After ATP block the number of vesicles at the active zone and CCV was reduced, with an increase in large vesicles. The possibility that RNS60 ASW acts by increasing mitochondrial ATP synthesis was tested by direct determination of ATP levels in both presynaptic and postsynaptic structures. This was implemented using luciferin/luciferase photon emission, which demonstrated a marked increase in ATP synthesis following RNS60 administration. It is concluded that RNS60 positively modulates synaptic transmission by up-regulating ATP synthesis, thus leading to synaptic transmission enhancement. PMID:24575037

Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: a possible mechanism of toxicity.

PubMed

Kay, H H; Grindle, K M; Magness, R R

2000-03-01

We undertook this investigation to explore the effects of ethanol exposure on nitric oxide synthase levels and nitric oxide release. Our hypothesis was that ethanol exposure modifies nitric oxide activity within the placenta as a result of oxidative stress. Four 10-g samples of term normal human placental villous tissue were perifused with nonrecirculating Dulbecco's modified Eagle's medium and 25-mmol/L N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] with 0-, 50-, 100-, or 200-mmol/L ethanol. After 2 hours of exposure, tissue was removed, fixed, and frozen for analysis. Immunohistochemical analysis was performed for subtype I or neuronal nitric oxide synthase (nNOS), subtype II or inducible nitric oxide synthase (iNOS), and subtype III or endothelial nitric oxide synthase (eNOS) localization. Western blot analysis was performed for eNOS quantitation. Cyclic guanosine monophosphate and copper-zinc superoxide dismutase levels were measured by electroimmunoassay and kinetic assay, respectively. Nitric oxide release was analyzed by a Sievers nitric oxide analyzer. Immunohistochemical examination confirmed that only eNOS was localized to the syncytiotrophoblasts. After ethanol exposure, eNOS protein expression increased 2.5- to 3.0-fold over that of the control. Tissue cyclic guanosine monophosphate content and nitric oxide release into the effluent were decreased, whereas superoxide dismutase levels were increased at higher ethanol levels (P <.05). Ethanol exposure appears to induce oxidative stress, which may account for the decreased nitric oxide release, because nitric oxide may be shunted toward scavenging free radicals. Increased eNOS protein expression may be a response to the increased demand for nitric oxide. Decreased nitric oxide availability could adversely affect placental blood flow regulation, which could, in turn, account for the growth restriction seen in ethanol-exposed fetuses.

Fast and slow active control of combustion instabilities in liquid-fueled combustors

NASA Astrophysics Data System (ADS)

Lee, Jae-Yeon

This thesis describes an experimental investigation of two different novel active control approaches that are employed to suppress combustion instabilities in liquid-fueled combustors. A "fast" active controller requires continuous modulation of the fuel injection rate at the frequency of the instability with proper phase and gain. Use of developed optical tools reveals that the "fast" active control system suppresses the instability by changing the nearly flat distribution of the phase between pressure and heat release oscillations to a gradually varying phase distribution, thus dividing the combustion zone into regions that alternately damp and drive combustor oscillations. The effects of these driving/damping regions tend to counter one another, which result in significant damping of the unstable oscillations. In contrast, a "slow" active controller operates at a rate commensurate with that at which operating conditions change during combustor operation. Consequently, "slow" controllers need infrequent activation in response to changes in engine operating conditions to assure stable operation at all times. Using two types of fuel injectors that can produce large controllable variation of fuel spray properties, it is shown that by changing the spray characteristics it is possible to significantly damp combustion instabilities. Similar to the aforementioned result of the "fast" active control study, "slow" change of the fuel spray properties also modifies the nearly flat phase distribution during unstable operation to a gradually varying phase distribution, resulting in combustor "stabilization". Furthermore, deconvolutions of CH*-chemiluminescence images reveal the presence of vortex-flame interaction during unstable operation. Strong driving of instabilities occurs where the mean axial velocity of the flow is approximately zero, a short distance downstream of the flame holder where a significant fraction of the fuel burns in phase with the pressure oscillations. It is shown that the "fast" and "slow" active control approaches suppress combustion instabilities in a different manner. Nevertheless, the both control approaches successfully suppress combustion instabilities by modifying the temporal and spatial behavior of the combustion process heat release that is responsible for driving the instability.

The effect of cyclodextrin on both the agglomeration and the in vitro characteristics of drug loaded and targeted silica nanoparticles

NASA Astrophysics Data System (ADS)

Khattabi, Areen M.; Alqdeimat, Diala A.

2018-02-01

One of the problems in the use of nanoparticles (NPs) as carriers in drug delivery systems is their agglomeration which mainly appears due to their high surface energy. This results in formation of NPs with different sizes leading to differences in their distribution and bioavailability. The surface coating of NPs with certain compounds can be used to prevent or minimize this problem. In this study, the effect of cyclodextrin (CD) on the agglomeration state and hence on the in vitro characteristics of drug loaded and targeted silica NPs was investigated. A sample of NPs was loaded with anticancer agents, then modified with a long polymer, carboxymethyl-β-cyclodextrin (CM-β-CD) and folic acid (FA), respectively. Another sample was modified similarly but without CD. The surface modification was characterized using fourier transform infrared spectroscopy (FT-IR). The polydispersity (PD) was measured using dynamic light scattering (DLS) and was found to be smaller for CD modified NPs. The results of the in vitro drug release showed that the release rate from both samples exhibited similar pattern for the first 5 hours, however the rate was faster from CD modified NPs after 24 hours. The in vitro cell viability assay confirmed that CD modified NPs were about 30% more toxic to HeLa cells. These findings suggest that CD has a clear effect in minimizing the agglomeration of such modified silica NPs, accelerating their drug release rate and enhancing their targeting effect.

Effects of Behavior-Contingent and Fixed-Time Release Contingencies on Frequency and Duration of Therapeutic Restraint

ERIC Educational Resources Information Center

Luiselli, James K.; Pace, Gary M.; Dunn, Erin K.

2006-01-01

Reducing therapeutic restraint is a desirable outcome for programs that serve individuals who exhibit challenging behaviors. This study investigated the effects of modifying the criterion for release from therapeutic restraint on frequency and duration. Release from restraint was changed from a behavior-contingent criterion (restraint terminated…

Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate).

PubMed

Zhang, F; McGinity, J W

2000-09-01

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70 degrees C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.

Multi-component hybrid hydrogels – understanding the extent of orthogonal assembly and its impact on controlled release† †Electronic supplementary information (ESI) available: Full experimental methods and further data from assays. See DOI: 10.1039/c7sc03301j Click here for additional data file.

PubMed Central

Vieira, Vânia M. P.; Hay, Laura L.

2017-01-01

This paper reports self-assembled multi-component hybrid hydrogels including a range of nanoscale systems and characterizes the extent to which each component maintains its own unique functionality, demonstrating that multi-functionality can be achieved by simply mixing carefully-chosen constituents. Specifically, the individual components are: (i) pH-activated low-molecular-weight gelator (LMWG) 1,3;2,4-dibenzylidenesorbitol-4′,4′′-dicarboxylic acid (DBS–COOH), (ii) thermally-activated polymer gelator (PG) agarose, (iii) anionic biopolymer heparin, and (iv) cationic self-assembled multivalent (SAMul) micelles capable of binding heparin. The LMWG still self-assembles in the presence of PG agarose, is slightly modified on the nanoscale by heparin, but is totally disrupted by the micelles. However, if the SAMul micelles are bound to heparin, DBS–COOH self-assembly is largely unaffected. The LMWG endows hybrid materials with pH-responsive behavior, while the PG provides mechanical robustness. The rate of heparin release can be controlled through network density and composition, with the LMWG and PG behaving differently in this regard, while the presence of the heparin binder completely inhibits heparin release through complexation. This study demonstrates that a multi-component approach can yield exquisite control over self-assembled materials. We reason that controlling orthogonality in such systems will underpin further development of controlled release systems with biomedical applications. PMID:29147525

Effective Anti-miRNA Oligonucleotides Show High Releasing Rate of MicroRNA from RNA-Induced Silencing Complex.

PubMed

Ariyoshi, Jumpei; Matsuyama, Yohei; Kobori, Akio; Murakami, Akira; Sugiyama, Hiroshi; Yamayoshi, Asako

2017-10-01

MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets. MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of miRNA from RISC is considered as an effective method for the inhibition of miRNA functions. In our previous study, we reported that anti-miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe) RNA, could induce the release of miRNA from RISC. However, the mechanisms underlying the miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-cancer drugs, are still unclear. In this study, we investigated the relationship between the miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC 50 ) using conventional chemically modified AMOs. We demonstrated that the miRNA-releasing effects of AMOs are directly proportional to the IC 50 values, and AMOs, which have an ability to promote the release of miRNA from RISC, can effectively inhibit RISC activity in living cells.

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.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.

PubMed

Zapata-Martín Del Campo, Carlos Manuel; Martínez-Rosas, Martín; Guarner-Lans, Verónica

2018-04-18

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease

PubMed Central

Zapata-Martín del Campo, Carlos Manuel; Martínez-Rosas, Martín

2018-01-01

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual. PMID:29670001

Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.

PubMed

Yamagata, Y; Iga, K; Ogawa, Y

2000-02-03

In order to develop a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs), we studied a model system using interferon-alpha (IFN-alpha) as the test protein. A cylindrical matrix was prepared by a heat extrusion technique using a lyophilized powder of the protein and 11 different types of synthetic PGEFs, which varied in degree of glycerol polymerization (di- and tetra-), chain length of fatty acids (myristate, palmitate and stearate) and degree of fatty acid esterification (mono-, di- and tri-). In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In contrast, the matrices prepared from tetraglycerol esters showed a steady rate of release without a large initial burst. In an in vivo release study, initial bursts of IFN-alpha release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-alpha was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-alpha release. Since the release rates from the matrices prepared from the tetraglycerol esters of palmitate and stearate were governed by Jander's equation modified for a cylindrical matrix, the release from those matrices was concluded to be a diffusion-controlled process. The bioavailability of IFN-alpha after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-alpha solution; consequently, IFN-alpha in these matrices appears to remain stable during the release period.

Effects of absorption enhancers in chloroquine suppository formulations: I. In vitro release characteristics.

PubMed

Onyeji, C O; Adebayo, A S; Babalola, C P

1999-12-01

The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates the effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositories. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. Results showed that the extent of drug release from suppositories containing any of three surfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release was obtained with control formulation (without enhancer) (P<0.05). However, Tween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in the rate of drug release from the suppositories. Sodium salicylate at a concentration of 25% (w/w) also significantly enhanced the drug release rate, but a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium salicylate did not significantly modify (P0.05) the rate of drug release when compared to the effect of the more effective single agent. Due to their effects in improving the drug release profiles coupled with their intrinsic absorption-promoting properties, it is suggested that incorporation of 4% (w/w) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an in vivo validation.

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE PAGES

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan; ...

2017-03-03

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

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

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia.

PubMed

Fitzgerald, Julie C; Weiss, Scott L; Maude, Shannon L; Barrett, David M; Lacey, Simon F; Melenhorst, J Joseph; Shaw, Pamela; Berg, Robert A; June, Carl H; Porter, David L; Frey, Noelle V; Grupp, Stephan A; Teachey, David T

2017-02-01

Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy. Retrospective cohort study. Academic children's hospital. Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor-modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495). All subjects received chimeric antigen receptor-modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab. Eighteen subjects (46%) developed grade 3-4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met criteria for acute respiratory distress syndrome. Encephalopathy, hepatic, and renal dysfunction manifested later than cardiovascular and respiratory dysfunction. Subjects had a median of 15 organ dysfunction days (interquartile range, 8-20). Treatment with tocilizumab in 13 subjects resulted in rapid defervescence (median, 4 hr) and clinical improvement. Grade 3-4 cytokine release syndrome occurred in 46% of patients following T cell therapy for relapsed/refractory acute lymphoblastic leukemia. Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers.

A Novel Approach for Dry Powder Coating of Pellets with Ethylcellulose. Part II: Evaluation of Caffeine Release.

PubMed

Albertini, Beatrice; Melegari, Cecilia; Bertoni, Serena; Dolci, Luisa Stella; Passerini, Nadia

2018-04-01

The objective of this study was to assess the efficacy and the capability of a novel ethylcellulose-based dry-coating system to obtain prolonged and stable release profiles of caffeine-loaded pellets. Lauric and oleic acids at a suitable proportion were used to plasticize ethylcellulose. The effect of coating level, percentage of drug loading, inert core particle size, and composition of the coating formulation including the anti-sticking agent on the drug release profile were fully investigated. A coating level of 15% w/w was the maximum layered amount which could modify the drug release. The best controlled drug release was obtained by atomizing talc (2.5% w/w) together with the solid plasticizer during the dry powder-coating process. SEM pictures revealed a substantial drug re-crystallization on the pellet surface, and the release studies evidenced that caffeine diffused through the plasticized polymer acting as pore former. Therefore, the phenomenon of caffeine migration across the coating layer had a strong influence on the permeability of the coating membrane. Comparing dry powder-coated pellets to aqueous film-coated ones, drug migration happened during storage, though more sustained release profiles were obtained. The developed dry powder-coating process enabled the production of stable caffeine sustained release pellets. Surprisingly, the release properties of the dry-coated pellets were mainly influenced by the way of addition of talc into the dry powder-coating blend and by the drug nature and affinity to the coating components. It would be interesting to study the efficacy of novel coating system using a different API.

Anti-biofilm action of nitric oxide-releasing alkyl-modified poly(amidoamine) dendrimers against Streptococcus mutans.

PubMed

Backlund, Christopher J; Worley, Brittany V; Schoenfisch, Mark H

2016-01-01

The effect of nitric oxide (NO)-releasing dendrimer hydrophobicity on Streptococcus mutans killing and biofilm disruption was examined at pH 7.4 and 6.4, the latter relevant to dental caries. Generation 1 (G1) poly(amidoamine) (PAMAM) dendrimers were modified with alkyl epoxides to generate propyl-, butyl-, hexyl-, octyl-, and dodecyl-functionalized dendrimers. The resulting secondary amines were reacted with NO to form N-diazeniumdiolate NO donor-modified dendrimer scaffolds (total NO ∼1μmol/mg). The bactericidal action of the NO-releasing dendrimers against both planktonic and biofilm-based S. mutans proved greatest with increasing alkyl chain length and at lower pH. Improved bactericidal efficacy at pH 6.4 was attributed to increased scaffold surface charge that enhanced dendrimer-bacteria association and ensuing membrane damage. For shorter alkyl chain (i.e., propyl and butyl) dendrimer modifications, increased antibacterial action at pH 6.4 was due to faster NO-release kinetics from proton-labile N-diazeniumdiolate NO donors. Octyl- and dodecyl-modified PAMAM dendrimers proved most effective for eradicating S. mutans biofilms with NO release mitigating dendrimer scaffold cytotoxicity. We report the antibacterial and anti-biofilm efficacy of dual-action nitric oxide (NO)-releasing dendrimers against S. mutans, an etiological agent in dental caries. This work was undertaken to enhance the anti-biofilm action of these scaffolds by employing various alkyl chain modifications. Furthermore, we evaluated the ability of NO to eradicate cariogenic biofilms. We found that at the lower pH associated with dental caries (pH ∼6.4), NO has a more pronounced antibacterial effect for alkyl modifications less capable of biofilm penetration and membrane disruption. Of greatest significance, we introduce dendrimers as a new macromolecular antibacterial agent against the cariogenic bacteria S. mutans. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Deaths, injuries, and evacuations from acute hazardous materials releases.

PubMed Central

Binder, S

1989-01-01

We examined reports from three surveillance systems of 587 acute releases of hazardous materials in 1986. These releases resulted in at least 115 deaths, 2,254 injuries, and 111 evacuations. Only eight (1 percent) of the 587 events were common to all three systems. Estimates of the public health consequences of hazardous materials releases could be improved by enforcing existing laws, modifying report forms, and validating collected information. PMID:2751024

The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development.

PubMed

Chung, Wilson C J; Linscott, Megan L; Rodriguez, Karla M; Stewart, Courtney E

2016-01-01

Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus-pituitary-gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success.

Evaluation of an injectable polymeric delivery system for controlled and localized release of biological factors to promote therapeutic angiogenesis

NASA Astrophysics Data System (ADS)

Rocker, Adam John

Cardiovascular disease remains as the leading cause of death worldwide and is frequently associated with partial or full occlusion of coronary arteries. Currently, angioplasty and bypass surgery are the standard approaches for treating patients with these ischemic heart conditions. However, a large number of patients cannot undergo these procedures. Therapeutic angiogenesis provides a minimally invasive tool for treating cardiovascular diseases by inducing new blood vessel growth from the existing vasculature. Angiogenic growth factors can be delivered locally through gene, cell, and protein therapy. Natural and synthetic polymer growth factor delivery systems are under extensive investigation due their widespread applications and promising therapeutic potential. Although biocompatible, natural polymers often suffer from batch-to-batch variability which can cause unpredictable growth factor release rates. Synthetic polymers offer advantages for growth factor delivery as they can be easily modified to control release kinetics. During the angiogenesis process, vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation while platelet-derived growth factor (PDGF) is needed later to help stabilize and mature new vessels. In the setting of myocardial infarction, additional anti-inflammatory cytokines like IL-10 are needed to help optimize cardiac repair and limit the damaging effects of inflammation following infarction. To meet these angiogenic and anti-inflammatory needs, an injectable polymer delivery system created from a sulfonated reverse thermal gel encapsulating micelle nanoparticles was designed and evaluated. The sulfonate groups on the thermal gel electrostatically bind to VEGF which controls its release rate, while the micelles are loaded with PDGF and are slowly released as the gel degrades. IL-10 was loaded into the system as well and diffused from the gel over time. An in vitro release study was performed which demonstrated the sequential release capabilities of the polymer system. The ability of the polymer system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response which showed that the polymer delivery system demonstrated a significant increase in functional and mature vessel formation while significantly reducing inflammation.

Time-dependent Mechanisms in Beta-cell Glucose Sensing

PubMed Central

Vagn Korsgaard, Thomas

2006-01-01

The relation between plasma glucose and insulin release from pancreatic beta-cells is not stationary in the sense that a given glucose concentration leads to a specific rate of insulin secretion. A number of time-dependent mechanisms appear to exist that modify insulin release both on a short and a longer time scale. Typically, two phases are described. The first phase, lasting up to 10 min, is a pulse of insulin release in response to fast changes in glucose concentration. The second phase is a more steady increase of insulin release over minutes to hours, if the elevated glucose concentration is sustained. The paper describes the glucose sensing mechanism via the complex dynamics of the key enzyme glucokinase, which controls the first step in glucose metabolism: phosphorylation of glucose to glucose-6-phosphate. Three time-dependent phenomena (mechanisms) are described. The fastest, corresponding to the first phase, is a delayed negative feedback regulating the glucokinase activity. Due to the delay, a rapid glucose increase will cause a burst of activity in the glucose sensing system, before the glucokinase is down-regulated. The second mechanism corresponds to the translocation of glucokinase from an inactive to an active form. As the translocation is controlled by the product(s) of the glucokinase reaction rather than by the substrate glucose, this mechanism gives a positive, but saturable, feedback. Finally, the release of the insulin granules is assumed to be enhanced by previous glucose exposure, giving a so-called glucose memory to the beta-cells. The effect depends on the insulin release of the cells, and this mechanism constitutes a second positive, saturable feedback system. Taken together, the three phenomena describe most of the glucose sensing behaviour of the beta-cells. The results indicate that the insulin release is not a precise function of the plasma glucose concentration. It rather looks as if the beta-cells just increase the insulin production, until the plasma glucose has returned to normal. This type of integral control has the advantage that the precise glucose sensitivity of the beta-cells is not important for normal glucose homeostasis. PMID:19669468

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan.

PubMed

El Maghraby, Gamal M; Elzayat, Ehab M; Alanazi, Fars K

2012-08-01

Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping. Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine. Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release. Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product. Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.

Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

NASA Astrophysics Data System (ADS)

Nguyen, Thao M.

Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes, while the control showed no visible drugs at the same depth. Most importantly, it was determined that the delivery of drugs into the blood stream was stable within 20 minutes. The functionalization of CP was also studied in order to enhance the properties and drug loading capabilities of the polymers. The co-polymerization of poly(3,4-(2-methylene)propylenedioxythiophene) (PMProDot) with polystyrene (PS) and polyvinylcarbazole (PVK) through the highly reactive methylene group was achieved. The modified PMProDot nanotubes demonstrated response times that were two times faster than without modification. The modification of PEDOT nanotubes with polydopamine, a biocompatible polymer, was also investigated and achieved. In depth characterization of functionalized CP demonstrate the ability to fine tune the properties of the polymer in order to achieve the required therapeutic drug release profile.

Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

PubMed

Leach, Jennie B; Schmidt, Christine E

2005-01-01

The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

Influence of lactose addition to gentamicin-loaded acrylic bone cement on the kinetics of release of the antibiotic and the cement properties.

PubMed

Frutos, Gloria; Pastor, José Ygnacio; Martínez, Noelia; Virto, María Rosa; Torrado, Susana

2010-03-01

The purpose of this study was to characterize a poly(methyl methacrylate) bone cement that was loaded with the antibiotic gentamicin sulphate (GS) and lactose, which served to modulate the release of GS from cement specimens. The release of GS when the cement specimens were immersed in phosphate-buffered saline at 37 degrees Celsius was determined spectrophotometrically. The microstructure, porosity, density, tensile properties and flexural properties of the cements were determined before and after release of GS. A kinetics model of the release of GS from the cement that involved a coupled mechanism based on dissolution/diffusion processes and an initial burst effect was proposed. Dissolution assay results showed that drug elution was controlled by a diffusion mechanism which can be modulated by lactose addition. Density values and mechanical properties (tensile strength, flexural strength, elastic modulus and fracture toughness) were reduced by the increased porosity resulting from lactose addition, but maintained acceptable values for the structural functions of bone cement. The present results suggest that lactose-modified, gentamicin-loaded acrylic bone cements are potential candidates for use in various orthopaedic and dental applications. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Controllable mineral coatings on PCL scaffolds as carriers for growth factor release

PubMed Central

Suárez-González, Darilis; Barnhart, Kara; Migneco, Francesco; Flanagan, Colleen; Hollister, Scott J.; Murphy, William L.

2011-01-01

In this study, we have developed mineral coatings on polycaprolactone scaffolds to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue in coatings formed in all HCO3 concentrations. Mineral coatings with increased HCO3 substitution showed more rapid dissolution kinetics in an environment deficient in calcium and phosphate but showed re-precipitation in an environment with the aforementioned ions. The mineral coating provided an effective mechanism for growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral mineral-coated PCL scaffolds. We also demonstrated sustained release of all growth factors with release kinetics that were strongly dependent in the solubility of the mineral coating. PMID:22014948

PEG-poly(amino acid) block copolymer micelles for tunable drug release.

PubMed

Ponta, Andrei; Bae, Younsoo

2010-11-01

To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

The use of sequential mark-release-recapture experiments to estimate population size, survival and dispersal of male mosquitoes of the  Anopheles gambiae complex in Bana, a west African humid savannah village.

PubMed

Epopa, Patric Stephane; Millogo, Abdoul Azize; Collins, Catherine Matilda; North, Ace; Tripet, Frederic; Benedict, Mark Quentin; Diabate, Abdoulaye

2017-08-07

Vector control is a major component of the malaria control strategy. The increasing spread of insecticide resistance has encouraged the development of new tools such as genetic control which use releases of modified male mosquitoes. The use of male mosquitoes as part of a control strategy requires an improved understanding of male mosquito biology, including the factors influencing their survival and dispersal, as well as the ability to accurately estimate the size of a target mosquito population. This study was designed to determine the seasonal variation in population size via repeated mark-release-recapture experiments and to estimate the survival and dispersal of male mosquitoes of the Anopheles gambiae complex in a small west African village. Mark-release-recapture experiments were carried out in Bana Village over two consecutive years, during the wet and the dry seasons. For each experiment, around 5000 (3407-5273) adult male Anopheles coluzzii mosquitoes were marked using three different colour dye powders (red, blue and green) and released in three different locations in the village (centre, edge and outside). Mosquitoes were recaptured at sites spread over the village for seven consecutive days following the releases. Three different capture methods were used: clay pots, pyrethroid spray catches and swarm sampling. Swarm sampling was the most productive method for recapturing male mosquitoes in the field. Population size and survival were estimated by Bayesian analyses of the Fisher-Ford model, revealing an about 10-fold increase in population size estimates between the end of dry season (10,000-50,000) to the wet season (100,000-500,000). There were no detectable seasonal effects on mosquito survival, suggesting that factors other than weather may play an important role. Mosquito dispersal ranged from 40 to 549 m over the seven days of each study and was not influenced by the season, but mainly by the release location, which explained more than 44% of the variance in net dispersal distance. This study clearly shows that male-based MRR experiments can be used to estimate some parameters of wild male populations such as population size, survival, and dispersal and to estimate the spatial patterns of movement in a given locality.

A long term study of fluoride release from metal-containing conventional and resin-modified glass-ionomer cements.

PubMed

Williams, J A; Billington, R W; Pearson, G J

2001-01-01

The objective of this study was to determine long term release of fluoride from a resin-modified glass-ionomer cement (RMGIC) (Fuji II LC (FLC)) compared with that from two conventional acid-base setting cements (HiDense (HD) and KetacSilver (KS)) marketed for similar restorative purposes. Fluoride release from discs of cement immersed in water or artificial saliva was measured for 2.7 years using an ion selective electrode technique. The RMGIC was affected by water if immersed immediately after setting. This is similar to conventional acid-base cements and the experimental method was designed to allow for this. Over the 2.7-year period, the RMGIC and HD released similar amounts of fluoride into both water and artificial saliva. In water, the RMGIC released the most fluoride, while in artificial saliva the highest release was from HD. KS released the least amount of fluoride in both immersing liquids. In artificial saliva, release was reduced to 17-25% of that found in water, with the RMGIC showing the greatest reduction. Both acid-base cured cements showed changes in colour over the 2.7-year span, while the colour of the RMGIC was stable. It was concluded that the RMGIC released equivalent or greater amounts of fluoride than the two acid-base cure glass-ionomers over a period of 2.7 years.

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.

Dual inhibitory action of enadoline (CI977) on release of amino acids in the rat hippocampus.

PubMed

Millan, M H; Chapman, A G; Meldrum, B S

1995-06-06

The effect of the kappa-opioid receptor agonist enadoline (CI977, (5R)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrilidinyl)-1-oxaspiro [4,5]dec-8-yl-4-benzofuranacetamide monohydrochloride), on the release of amino acids was studied in the hippocampus of freely moving rats. K+, 100 mM, or veratrine, 100 microM, were applied for 10 min via the dialysis probe, either alone (control groups) or together with CI977 (after a 10 min pretreatment with CI977 in the perfusion medium). To test the specificity of the response to CI977, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was delivered together with CI977 in two groups of animals. To test the effect of systemic injection, CI977 was given subcutaneously 30 min prior to either stimulus. K(+)-induced release of glutamate and aspartate was significantly reduced by CI977, 2.5 mM; release of gamma-aminobutyric acid (GABA) was reduced by 250 microM CI977 in the probe. The effect of CI977 on release of glutamate and aspartate, but not of GABA, was reversed by nor-binaltorphimine (45 microM). Systemic treatment with CI977, 1 or 10 mg/kg, did not reduce K(+)-induced release of glutamate. Veratrine-induced release of aspartate and glutamate was significantly inhibited by 25 microM and release of GABA by 250 microM CI977 in the probe, and this effect was not modified by nor-binaltorphimine (58 microM). Systemic injection of CI977 1 mg/kg significantly reduced veratrine-induced release of glutamate. These results indicate that CI977 regulates release of amino acids by two independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents

PubMed Central

Lu, Yuan; Slomberg, Danielle L.; Schoenfisch, Mark H.

2014-01-01

Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ~2500, 5000, 10000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro. PMID:24268196

Controlled release of an extract of Calendula officinalis flowers from a system based on the incorporation of gelatin-collagen microparticles into collagen I scaffolds: design and in vitro performance.

PubMed

Jiménez, Ronald A; Millán, Diana; Suesca, Edward; Sosnik, Alejandro; Fontanilla, Marta R

2015-06-01

Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries.

Vasopressin synthesis by the magnocellular neurons is different in the supraoptic nucleus and in the paraventricular nucleus in human and experimental septic shock.

PubMed

Sonneville, Romain; Guidoux, Céline; Barrett, Lucinda; Viltart, Odile; Mattot, Virginie; Polito, Andrea; Siami, Shidasp; de la Grandmaison, Geoffroy Lorin; Blanchard, Anne; Singer, Mervyn; Annane, Djillali; Gray, Françoise; Brouland, Jean-Philippe; Sharshar, Tarek

2010-05-01

Impaired arginine vasopressin (AVP) synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnocellular neurons of the paraventricular and supraoptic nuclei, have been postulated in septic shock, but changes in this system have never been assessed in human septic shock, and only partially experimentally. We investigated AVP synthesis and release by the neurohypophyseal system in 9 patients who died from septic shock and 10 controls, and in 20 rats with fecal peritonitis-induced sepsis and 8 sham-operation controls. Ten rats died spontaneously from septic shock, and the others were sacrificed. In patients with septic shock, as in rats that died spontaneously following sepsis induction, AVP immunohistochemical expression was decreased in the neurohypophysis and supraoptic magnocellular neurons, whereas it was increased in the paraventricular magnocellular neurons. No significant change was observed in AVP messenger RiboNucleic Acid (mRNA) expression assessed by in situ hybridization in either paraventricular or supraoptic magnocellular cells. This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei.

Vesicular Egress of Non-Enveloped Lytic Parvoviruses Depends on Gelsolin Functioning

PubMed Central

Bär, Séverine; Daeffler, Laurent; Rommelaere, Jean; Nüesch, Jürg P. F.

2008-01-01

The autonomous parvovirus Minute Virus of Mice (MVM) induces specific changes in the cytoskeleton filaments of infected permissive cells, causing in particular the degradation of actin fibers and the generation of “actin patches.” This is attributed to a virus-induced imbalance between the polymerization factor N-WASP (Wiscott-Aldrich syndrome protein) and gelsolin, a multifunctional protein cleaving actin filaments. Here, the focus is on the involvement of gelsolin in parvovirus propagation and virus-induced actin processing. Gelsolin activity was knocked-down, and consequences thereof were determined for virus replication and egress and for actin network integrity. Though not required for virus replication or progeny particle assembly, gelsolin was found to control MVM (and related H1-PV) transport from the nucleus to the cell periphery and release into the culture medium. Gelsolin-dependent actin degradation and progeny virus release were both controlled by (NS1)/CKIIα, a recently identified complex between a cellular protein kinase and a MVM non-structural protein. Furthermore, the export of newly synthesized virions through the cytoplasm appeared to be mediated by (virus-modified) lysomal/late endosomal vesicles. By showing that MVM release, like entry, is guided by the cytoskeleton and mediated by vesicles, these results challenge the current view that egress of non-enveloped lytic viruses is a passive process. PMID:18704167

The Time Required for Dormancy Release in Arabidopsis Is Determined by DELAY OF GERMINATION1 Protein Levels in Freshly Harvested Seeds[OA

PubMed Central

Nakabayashi, Kazumi; Bartsch, Melanie; Xiang, Yong; Miatton, Emma; Pellengahr, Silke; Yano, Ryoichi; Seo, Mitsunori; Soppe, Wim J.J.

2012-01-01

Seed dormancy controls the start of a plant’s life cycle by preventing germination of a viable seed in an unfavorable season. Freshly harvested seeds usually show a high level of dormancy, which is gradually released during dry storage (after-ripening). Abscisic acid (ABA) has been identified as an essential factor for the induction of dormancy, whereas gibberellins (GAs) are required for germination. The molecular mechanisms controlling seed dormancy are not well understood. DELAY OF GERMINATION1 (DOG1) was recently identified as a major regulator of dormancy in Arabidopsis thaliana. Here, we show that the DOG1 protein accumulates during seed maturation and remains stable throughout seed storage and imbibition. The levels of DOG1 protein in freshly harvested seeds highly correlate with dormancy. The DOG1 protein becomes modified during after-ripening, and its levels in stored seeds do not correlate with germination potential. Although ABA levels in dog1 mutants are reduced and GA levels enhanced, we show that DOG1 does not regulate dormancy primarily via changes in hormone levels. We propose that DOG1 protein abundance in freshly harvested seeds acts as a timer for seed dormancy release, which functions largely independent from ABA. PMID:22829147

Controlled extended octenidine release from a bacterial nanocellulose/Poloxamer hybrid system.

PubMed

Alkhatib, Y; Dewaldt, M; Moritz, S; Nitzsche, R; Kralisch, D; Fischer, D

2017-03-01

Although bacterial nanocellulose (BNC) has been widely investigated in the last 10years as drug delivery system, up to now no long-term controlled release of drugs could be realized. Therefore, the aim of the present work was the development of a BNC-based drug delivery system that provides prolonged retention time for the antiseptic octenidine up to one week with improved mechanical and antimicrobial properties as well as a high biocompatibility. BNC was modified by incorporation of differently concentrated Poloxamers 338 and 407 as micelles and gels that were extensively investigated regarding size, surface charge, and dynamic viscosity. Depending on type and concentration of the Poloxamer, a retarded octenidine release up to one week could be accomplished. Additionally, superior material properties such as high compression stability and water binding could be achieved. The antimicrobial activity of octenidine against Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of Poloxamers. Excellent biocompatibility of the Poloxamer loaded BNC could be demonstrated after local administration in a shell-less hen's egg model. In conclusion, a long-term delivery system consisting of BNC and Poloxamer could be developed for octenidine as a ready-to-use system e.g. for long-term dermal wound treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct and indirect effects of invasive plants on soil chemistry and ecosystem function.

PubMed

Weidenhamer, Jeffrey D; Callaway, Ragan M

2010-01-01

Invasive plants have a multitude of impacts on plant communities through their direct and indirect effects on soil chemistry and ecosystem function. For example, plants modify the soil environment through root exudates that affect soil structure, and mobilize and/or chelate nutrients. The long-term impact of litter and root exudates can modify soil nutrient pools, and there is evidence that invasive plant species may alter nutrient cycles differently from native species. The effects of plants on ecosystem biogeochemistry may be caused by differences in leaf tissue nutrient stoichiometry or secondary metabolites, although evidence for the importance of allelochemicals in driving these processes is lacking. Some invasive species may gain a competitive advantage through the release of compounds or combinations of compounds that are unique to the invaded community—the “novel weapons hypothesis.” Invasive plants also can exert profound impact on plant communities indirectly through the herbicides used to control them. Glyphosate, the most widely used herbicide in the world, often is used to help control invasive weeds, and generally is considered to have minimal environmental impacts. Most studies show little to no effect of glyphosate and other herbicides on soil microbial communities. However, herbicide applications can reduce or promote rhizobium nodulation and mycorrhiza formation. Herbicide drift can affect the growth of non-target plants, and glyphosate and other herbicides can impact significantly the secondary chemistry of plants at sublethal doses. In summary, the literature indicates that invasive species can alter the biogeochemistry of ecosystems, that secondary metabolites released by invasive species may play important roles in soil chemistry as well as plant-plant and plant-microbe interactions, and that the herbicides used to control invasive species can impact plant chemistry and ecosystems in ways that have yet to be fully explored.

A Phase 2 Study of Chronocort, a Modified-Release Formulation of Hydrocortisone, in the Treatment of Adults With Classic Congenital Adrenal Hyperplasia

PubMed Central

Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J.; Daley, Lori-Ann; Digweed, Dena; Eckland, David J. A.; Van Ryzin, Carol; Nieman, Lynnette K.; Arlt, Wiebke; Merke, Deborah P.

2015-01-01

Context: Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. Objectives: The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Design, Setting, and Patients: Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. Main Outcome Measures: The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). Results: In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700–1500 h; P = .002), and afternoon (1500–2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700–1500 h; P = .02) 17-OHP AUC. Conclusions: Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH. PMID:25494662

A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia.

PubMed

Mallappa, Ashwini; Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J; Daley, Lori-Ann; Digweed, Dena; Eckland, David J A; Van Ryzin, Carol; Nieman, Lynnette K; Arlt, Wiebke; Ross, Richard J; Merke, Deborah P

2015-03-01

Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700-1500 h; P = .002), and afternoon (1500-2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700-1500 h; P = .02) 17-OHP AUC. Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.

Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model

PubMed Central

Moser, Sydney; Lim, Jongbin; Chegeni, Mohammad; Wightman, JoLynne D.; Hamaker, Bruce R.; Ferruzzi, Mario G.

2016-01-01

While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%–11.5% inhibition; p < 0.05). Separately, all GJ extracts (10–100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%–38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%–15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%–38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID:27399765

The use of a combination of different MR methods to study swelling of hydrophilic xanthan matrix tablets at different pHs.

PubMed

Mikac, U; Sepe, A; Kristl, J; Baumgartner, I

2012-01-01

Modified-release matrix tablets have been extensively used by the pharmaceutical industry as one of the most successful oral drug-delivery systems. The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. Magnetic resonance imaging (MRI) is a powerful, non-invasive technique that can help improve our understanding of the gel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on the drug release. The aim was to investigate the effects of pH and ionic strength on swelling and to study the influence of structural changes in xanthan gel on drug release. For this purpose a combination of different MRI methods for accurate determination of penetration, swelling and erosion fronts was used. The position of the penetration and swelling fronts were the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers.

Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

NASA Astrophysics Data System (ADS)

Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

2015-09-01

Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

Characterization of drug release from liposomal formulations in ocular fluid.

PubMed

Jafari, M R; Jones, A B; Hikal, A H; Williamson, J S; Wyandt, C M

1998-01-01

The successful application of liposomes in topical ophthalmic drug delivery requires knowledge of vesicle stabilization in the presence of tear fluid. The release of procaine hydrochloride (PCH) from large unilamellar liposomes in the presence of simulated tear fluid was studied in vitro as a function of bilayer lipid content and tear protein composition. Reverse-phase evaporation vesicles were prepared from egg phosphatidylcholine, stearylamine or dicetyl phosphate, and cholesterol. The relationship between lipid composition and encapsulation efficiency, vesicle size, drug leakage upon storage at 4 degrees C, and the release of PCH-loaded liposomes was studied. The encapsulation efficiency was found to be dependent upon the lipid composition used in the liposome preparation. In particular, phosphatidylcholine vesicles containing cholesterol and/or charged lipids had a lower entrapment efficiency than liposomes prepared with phosphatidylcholine alone. However, the drug release rate was reduced significantly by inclusion of cholesterol and/or charged lipids in the liposomes. The release kinetics of the entrapped agent seemed to be a biphasic process and the drug-release in both simulated tear fluid (STF) and pH 7.4 phosphate buffered saline (PBS) solutions followed pseudo first-order kinetics in the early stage of the release profile. The drug-release appeared to be diffusion and/or partition controlled. Drug release from liposomes into STF, pH 7.4 PBS, and five different modified tear formulations was also evaluated. While serum-induced leakage is attributed to high-density lipoprotein-mediated destabilization, it was determined that lactoferrin might be the protein component in tear fluid that has the primary influence on the liposome-entrapped drug release rate. Five local anesthetics, benoxinate, proparacaine, procaine, tetracaine, and benzocaine were entrapped in liposomal vesicles by a reverse-phase evaporation (REV) technique. The release of these structurally similar topical anesthetics entrapped in positively charged liposomes (egg phosphatidylcholine, stearylamine, and cholesterol in a 7:2:1 molar ratio) was evaluated in a simulated tear fluid and pH 7.4 phosphate buffered saline solution. The liposomes appeared to be useful carriers for these drugs to retard their in vitro release in tear fluid and perhaps sustain or control their release in the eye for better therapeutic efficacy. An analysis of the release data demonstrated that for this series of drugs, drug partition coefficient has the largest effect on release rate, with molecular weight exhibiting a smaller effect. Release rate was found to decrease with increased lipophilicity or increased molecular weight.

Biological Control Strategies for Mosquito Vectors of Arboviruses.

PubMed

Huang, Yan-Jang S; Higgs, Stephen; Vanlandingham, Dana L

2017-02-10

Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses.

Sterile-Insect Methods for Control of Mosquito-Borne Diseases: An Analysis

PubMed Central

Benedict, Mark; Bellini, Romeo; Clark, Gary G.; Dame, David A.; Service, Mike W.; Dobson, Stephen L.

2010-01-01

Abstract Effective vector control, and more specifically mosquito control, is a complex and difficult problem, as illustrated by the continuing prevalence (and spread) of mosquito-transmitted diseases. The sterile insect technique and similar methods control certain agricultural insect pest populations in a species-specific, environmentally sound, and effective manner; there is increased interest in applying this approach to vector control. Such an approach, like all others in use and development, is not a one-size-fits-all solution, and will be more appropriate in some situations than others. In addition, the proposed release of pest insects, and more so genetically modified pest insects, is bound to raise questions in the general public and the scientific community as to such a method's efficacy, safety, and sustainability. This article attempts to address these concerns and indicate where sterile-insect methods are likely to be useful for vector control. PMID:19725763

Biological Control Strategies for Mosquito Vectors of Arboviruses

PubMed Central

Huang, Yan-Jang S.; Higgs, Stephen; Vanlandingham, Dana L.

2017-01-01

Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses. PMID:28208639

Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil.

PubMed

Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir

2017-09-01

In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1 H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Building an Efficient Model for Afterburn Energy Release

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

Alves, S; Kuhl, A; Najjar, F

2012-02-03

Many explosives will release additional energy after detonation as the detonation products mix with the ambient environment. This additional energy release, referred to as afterburn, is due to combustion of undetonated fuel with ambient oxygen. While the detonation energy release occurs on a time scale of microseconds, the afterburn energy release occurs on a time scale of milliseconds with a potentially varying energy release rate depending upon the local temperature and pressure. This afterburn energy release is not accounted for in typical equations of state, such as the Jones-Wilkins-Lee (JWL) model, used for modeling the detonation of explosives. Here wemore » construct a straightforward and efficient approach, based on experiments and theory, to account for this additional energy release in a way that is tractable for large finite element fluid-structure problems. Barometric calorimeter experiments have been executed in both nitrogen and air environments to investigate the characteristics of afterburn for C-4 and other materials. These tests, which provide pressure time histories, along with theoretical and analytical solutions provide an engineering basis for modeling afterburn with numerical hydrocodes. It is toward this end that we have constructed a modified JWL equation of state to account for afterburn effects on the response of structures to blast. The modified equation of state includes a two phase afterburn energy release to represent variations in the energy release rate and an afterburn energy cutoff to account for partial reaction of the undetonated fuel.« less

Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics.

PubMed

Schulze, Jennifer; Kaiser, Odett; Paasche, Gerrit; Lamm, Hans; Pich, Andreas; Hoffmann, Andrea; Lenarz, Thomas; Warnecke, Athanasia

2017-01-01

Hyperbaric oxygen therapy (HBOT) is a noninvasive widely applied treatment that increases the oxygen pressure in tissues. In cochlear implant (CI) research, intracochlear application of neurotrophic factors (NTFs) is able to improve survival of spiral ganglion neurons (SGN) after deafness. Cell-based delivery of NTFs such as brain-derived neurotrophic factor (BDNF) may be realized by cell-coating of the surface of the CI electrode. Human mesenchymal stem cells (MSC) secrete a variety of different neurotrophic factors and may be used for the development of a biohybrid electrode in order to release endogenously-derived neuroprotective factors for the protection of residual SGN and for a guided outgrowth of dendrites in the direction of the CI electrode. HBOT could be used to influence cell behaviour after transplantation to the inner ear. The aim of this study was to investigate the effect of HBOT on the proliferation, BDNF-release and secretion of neuroprotective factors. Thus, model cells (an immortalized fibroblast cell line (NIH3T3)-native and genetically modified) and MSCs were repeatedly (3 x - 10 x) exposed to 100% oxygen at different pressures. The effects of HBO on cell proliferation were investigated in relation to normoxic and normobaric conditions (NOR). Moreover, the neuroprotective and neuroregenerative effects of HBO-treated cells were analysed by cultivation of SGN in conditioned medium. Both, the genetically modified NIH3T3/BDNF and native NIH3T3 fibroblasts, showed a highly significant increased proliferation after five days of HBOT in comparison to normoxic controls. By contrast, the number of MSCs was decreased in MSCs treated with 2.0 bar of HBO. Treating SGN cultures with supernatants of fibroblasts and MSCs significantly increased the survival rate of SGN. HBO treatment did not influence (increase / reduce) this effect. Secretome analysis showed that HBO treatment altered the protein expression pattern in MSCs.

Design, characterization and in vitro evaluation of a novel thiolated polymer: preactivated carboxymethyl cellulose.

PubMed

Laffleur, Flavia; Bacher, Lukas; Netsomboon, Kesinee

2016-01-01

To design a novel preactived carboxymethyl cellulose derivative. First, carboxymethyl cellulose (CMC) was chemically modified by amide bond formation between primary amino group of cysteine (CYS) and carboxylic moiety of CMC mediated by carbodiimide. Second, obtained CMCCYS was preactivated with 2,2'-dithiodinicotinic acid. Designed CMC-S-S-MNA was characterized by FT-IR. Furthermore, cytotoxicity was conducted on Caco-2 cell line. Swelling behavior, erosion and release of novel CMC-S-S-MNA were performed compared with thiolated and unmodified cellulose, respectively. CMC-S-S-MNA showed no harmful effect on cells. CMC-S-S-MNA exhibited 2.13-fold higher stability in comparison to unmodified cellulose. Furthermore, preactivated carboxymethyl cellulose-cysteine revealed 1.9-fold controlled released compared with respective unmodified carboxymethyl cellulose. Novel preactivated carboxymethyl cellulose represents a versatile excipient for drug delivery.

PTX-loaded three-layer PLGA/CS/ALG nanoparticle based on layer-by-layer method for cancer therapy.

PubMed

Wang, Fang; Yuan, Jian; Zhang, Qian; Yang, Siqian; Jiang, Shaohua; Huang, Chaobo

2018-05-17

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are an ideal paclitaxel (PTX)-carrying system due to its biocompatibility and biodegradability. But it possessed disadvantage of drug burst release. In this research, a layer-by-layer deposition of chitosan (CS) and sodium alginate (ALG) was applied to modify the PLGA nanoparticles. The surface charges and morphology of the PLGA, PLGA/CS and PLGA/CS/ALG particles was measured by capillary electrophoresis and SEM and TEM, respectively. The drug encapsulation and loading efficiency were confirmed by ultraviolet spectrophotometer. The nanoparticles were stable and exhibited controlled drug release performance, with good cytotoxicity to human lung carcinoma cells (HepG 2). Cumulatively, our research suggests that this kind of three-layer nanoparticle with LbL-coated shield has great properties to act as a novel drug-loaded system.

Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

PubMed

Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

2015-08-12

A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100.

PubMed

El Maghraby, Gamal Mohamed; Elzayat, Ehab Mostafa; Alanazi, Fars Kaed

2014-03-01

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.

TSCA Environmental Release Application (TERA) for Modified Pseudomonas Fluorescens

EPA Pesticide Factsheets

TERA submitted by Micro Systems Technologies, LLC and given the tracking designations of R-02-0001. The microorganism has been genetically modified to contain a bioluminescent gene that is activated upon metabolism of naphthalene and/or methyl salicylate.

Restoring Natural Streamflow Variability by Modifying Multi-purpose Reservoir Operation

NASA Astrophysics Data System (ADS)

Shiau, J.

2010-12-01

Multi-purpose reservoirs typically provide benefits of water supply, hydroelectric power, and flood mitigation. Hydroelectric power generations generally do not consume water. However, temporal distribution of downstream flows is highly changed due to hydro-peaking effects. Associated with offstream diversion of water supplies for municipal, industrial, and agricultural requirements, natural streamflow characteristics of magnitude, duration, frequency, timing, and rate of change is significantly altered by multi-purpose reservoir operation. Natural flow regime has long been recognized a master factor for ecosystem health and biodiversity. Restoration of altered flow regime caused by multi-purpose reservoir operation is the main objective of this study. This study presents an optimization framework that modifying reservoir operation to seeking balance between human and environmental needs. The methodology presented in this study is applied to the Feitsui Reservoir, located in northern Taiwan, with main purpose of providing stable water-supply and auxiliary purpose of electricity generation and flood-peak attenuation. Reservoir releases are dominated by two decision variables, i.e., duration of water releases for each day and percentage of daily required releases within the duration. The current releasing policy of the Feitsui Reservoir releases water for water-supply and hydropower purposes during 8:00 am to 16:00 pm each day and no environmental flows releases. Although greater power generation is obtained by 100% releases distributed within 8-hour period, severe temporal alteration of streamflow is observed downstream of the reservoir. Modifying reservoir operation by relaxing these two variables and reserve certain ratio of streamflow as environmental flow to maintain downstream natural variability. The optimal reservoir releasing policy is searched by the multi-criterion decision making technique for considering reservoir performance in terms of shortage ratio and power generation and downstream hydrologic alterations in terms of ecological relevant indicators. The results show that the proposed methodology can mitigate hydro-peaking effects on natural variability, while maintains efficient reservoir operation.

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

PubMed

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

ANOPP programmer's reference manual for the executive System. [aircraft noise prediction program

NASA Technical Reports Server (NTRS)

Gillian, R. E.; Brown, C. G.; Bartlett, R. W.; Baucom, P. H.

1977-01-01

Documentation for the Aircraft Noise Prediction Program as of release level 01/00/00 is presented in a manual designed for programmers having a need for understanding the internal design and logical concepts of the executive system software. Emphasis is placed on providing sufficient information to modify the system for enhancements or error correction. The ANOPP executive system includes software related to operating system interface, executive control, and data base management for the Aircraft Noise Prediction Program. It is written in Fortran IV for use on CDC Cyber series of computers.

TSCA Environmental Release Application (TERA) for Modified Escherichia coli

EPA Pesticide Factsheets

TERA submitted by University of North Carolina and given tracking designation of R-01-0001. The microorganism will be introduced into potential sources of fecal contamination to determine if the bacteria can be detected downstream from the release points.

Efficient Self-Assembly of mPEG End-Capped Porous Silica as a Redox-Sensitive Nanocarrier for Controlled Doxorubicin Delivery.

PubMed

Nguyen, Anh Khoa; Nguyen, Thi Hiep; Bao, Bui Quoc; Bach, Long Giang; Nguyen, Dai Hai

2018-01-01

Porous nanosilica (PNS) has been regarded as a promising candidate for controlled delivery of anticancer drugs. Unmodified PNS-based nanocarriers, however, showed a burst release of encapsulated drugs, which may limit their clinical uses. In this report, PNS was surface conjugated with adamantylamine (ADA) via disulfide bridges (-SS-), PNS-SS-ADA, which was further modified with cyclodextrin-poly(ethylene glycol) methyl ether conjugate (CD-mPEG) to form a core@shell structure PNS-SS-ADA@CD-mPEG for redox triggered delivery of doxorubicin (DOX), DOX/PNS-SS-ADA@CD-mPEG. The prepared PNS-SS-ADA@CD-mPEG nanoparticles were spherical in shape with an average diameter of 55.5 ± 3.05 nm, a little larger than their parentally PNS nanocarriers, at 49.6 ± 2.56 nm. In addition, these nanoparticles possessed high drug loading capacity, at 79.2 ± 3.2%, for controlled release. The release of DOX from DOX/PNS-SS-ADA@CD-mPEG nanoparticles was controlled and prolonged up to 120 h in PBS medium (pH 7.4), compared to less than 40 h under reducing condition of 5 mM DTT. Notably, the PNS-SS-ADA@CD-mPEG was a biocompatible nanocarrier, and the toxicity of DOX was dramatically reduced after loading drugs into the porous core. This redox-sensitive PNS-SS-ADA@CD-mPEG nanoparticle could be considered a potential candidate with high drug loading capacity and a lower risk of systemic toxicity.

Impacts of select organic ligands on the colloidal stability, dissolution dynamics, and toxicity of silver nanoparticles.

PubMed

Pokhrel, Lok R; Dubey, Brajesh; Scheuerman, Phillip R

2013-11-19

Key understanding of potential transformations that may occur on silver nanoparticle (AgNP) surface upon interaction with naturally ubiquitous organic ligands (e.g., -SH (thoil), humic acid, or -COO (carboxylate)) is limited. Herein we investigated how dissolved organic carbon (DOC), -SH (in cysteine, a well-known Ag(+) chelating agent), and -COO (in trolox, a well-known antioxidant) could alter the colloidal stability, dissolution rate, and toxicity of citrate-functionalized AgNPs (citrate-AgNPs) against a keystone crustacean Daphnia magna. Cysteine, DOC, or trolox amendment of citrate-AgNPs differentially modified particle size, surface properties (charge, plasmonic spectra), and ion release dynamics, thereby attenuating (with cysteine or trolox) or promoting (with DOC) AgNP toxicity. Except with DOC amendment, the combined toxicity of AgNPs and released Ag under cysteine or trolox amendment was lower than of AgNO3 alone. The results of this study show that citrate-AgNP toxicity can be associated with oxidative stress, ion release, and the organism biology. Our evidence suggests that specific organic ligands available in the receiving waters can differentially surface modify AgNPs and alter their environmental persistence (changing dissolution dynamics) and subsequently the toxicity; hence, we caveat to generalize that surface modified nanoparticles upon environmental release may not be toxic to receptor organisms.

Meletin sustained-release gliadin nanoparticles prepared via solvent surface modification on blending electrospraying

NASA Astrophysics Data System (ADS)

Yang, Yao-Yao; Zhang, Man; Liu, Zhe-Peng; Wang, Ke; Yu, Deng-Guang

2018-03-01

Almost all electrospraying processes are carried out under an air-solution interface, thereby overlooking the potential influence of an additional solvent surface modification between air and the working solution. A pure solvent was explored to temporarily and dynamically surround the solutions utilized for blending electrospraying, which contained a guest drug meletin and a protein drug carrier gliadin. The new modified processes created protein-based medicated nanoparticles (P2) with higher quality than their counterparts (P1) from blending processes, as demonstrated by the SEM and TEM images. Although the particles from the two processes were similar (nanocomposites), and the particles P1 were larger than P2, the later provided a better meletin sustained-release profile than the former. This finding was verified by the smaller initial burst release, longer sustained-release time period, and shorter late leveling-off stage. These unanticipated results were attributed to the rounder surface, the more uniform size distribution, and the smaller total surface area of particles P2 than P1. The microformation mechanism of the modified coaxial process was suggested. The protocols reported here paved a new way for the development of new kinds of functional nanoparticles by modifying the interfaces of working fluids during electrospraying.

Octacosanol educes physico-chemical attributes, release and bioavailability as modified nanocrystals.

PubMed

Sen Gupta, Surashree; Ghosh, Mahua

2017-10-01

Octacosanol is a lesser known nutraceutical with the potential for treatment of several inflammatory diseases, high cholesterol, Parkinson's symptoms and tumour growth along with the capacity to improve athletic performance. But its lipophilicity and large structure inhibits extended solubility in water resulting in poor absorption and a low bioavailability. In the present work, sodium salt of octacosyl sulfate was synthesized. It displayed improved water solubility. Its nanocrystals, synthesized by means of nanoprecipitation technique, enhanced diffusion velocity, antioxidant capacity, shelf-life, penetrability and bioavailability. Particle size of the nanocrystals ranged between 197 and 220nm. Both modified octacosanol and its nanocrystals displayed maximum lipid peroxidation activities at a concentration 1000ppm, but nanocrystals demonstrated higher prevention. From freeze-thaw cycles it was evident that normal octacosanol crystals were far more prone to temperature variations than the nanocrystals. A pronounced increase in release/diffusion rate and bioavailability was observed for the nanocrystals of the modified octacosanol. In vitro release kinetics, bioavailability and bioequivalence were studied. Relative bioavailability for gastric passage and pancreatic passage of nanocrystals was 2.58 times and 1.81 times that of normal crystals respectively. Furthermore the nanocrystals displayed a superior in vitro release rate, while following a non-Fickian mode. Copyright © 2017 Elsevier B.V. All rights reserved.

Response to luteinizing releasing hormone, thyrotrophic releasing hormone, and human chorionic gonadotropin administration in healthy men at different risks for prostatic cancer and in prostatic cancer patients.

PubMed

Hill, P; Wynder, E L; Garbaczewski, L; Garnes, H; Walker, A R

1982-05-01

A comparative study of the pituitary and testicular response to luteinizing releasing hormone (LHRH), thyrotrophic releasing hormone (TRH), and human chorionic gonadotrophin (HCG) administration was carried out in (a) low-risk young South African black men and high-risk North American black men for prostatic cancer and (b) healthy elderly South African men and South African black men with prostatic cancer. A comparable HCG response occurred in young South African and North American black men, while a greater release of prolactin, but a lesser release of luteinizing hormone in response to LHRH:TRH occurred in South African black men. The response to HCG was comparable in elderly and young South African black men, although the prolactin release in response to TRH was greater in elderly men. A more prolonged release of luteinizing hormone was evident in men with prostatic cancer. Higher estradiol and estrone but lower androstenedione levels occurred in men with prostatic cancer. Data suggest that, in the elderly South African black men with prostatic cancer, estrogen metabolism is modified and that either the estrogen level or the higher estrogen:androgen levels modify the pituitary response to LHRH:TRH. A Western diet enhanced the changes in hormone profiles evident in black South African men with prostatic cancer.

Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

PubMed

Qiu, Yihong; Li, Xia; Duan, John Z

2014-02-01

The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Investigation on extracellular polymeric substances, sludge flocs morphology, bound water release and dewatering performance of sewage sludge under pretreatment with modified phosphogypsum.

PubMed

Dai, Quxiu; Ma, Liping; Ren, Nanqi; Ning, Ping; Guo, Zhiying; Xie, Longgui; Gao, Haijun

2018-06-06

Modified phosphogypsum (MPG) was developed to improve dewaterability of sewage sludge, and dewatering performance, properties of treated sludge, composition and morphology distribution of EPS, dynamic analysis and multiple regression model on bound water release were investigated. The results showed that addition of MPG caused extracellular polymeric substances (EPS) disintegration through charge neutralization. Destruction of EPS promoted the formation of larger sludge flocs and the release of bound water into supernatant. Simultaneously, content of organics with molecular weight between 1000 and 7000 Da in soluble EPS (SB-EPS) increased with increasing of EPS dissolved into the liquid phase. Besides, about 8.8 kg•kg -1 DS of bound water was released after pretreatment with 40%DS MPG dosage. Additionally, a multiple linear regression model for bound water release was established, showing that lower loosely bond EPS (LB-EPS) content and specific resistance of filtration (SRF) may improve dehydration performance, and larger sludge flocs may be beneficial for sludge dewatering. Copyright © 2018 Elsevier Ltd. All rights reserved.

European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

PubMed

Ekman, Bertil; Fitts, David; Marelli, Claudio; Murray, Robert D; Quinkler, Marcus; Zelissen, Pierre M J

2014-05-09

Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK and Sweden, with recruitment soon to be initiated in the Netherlands. EU-AIR will provide a unique opportunity not only to collect long-term safety data on a modified-release preparation of glucocorticoid but also to evaluate baseline data on conventional glucocorticoid replacement. Such data should help to improve the treatment of AI.

Immobilization of sericin molecules via amorphous carbon plasma modified-polystyrene dish for serum-free culture

NASA Astrophysics Data System (ADS)

Tunma, Somruthai; Song, Doo-Hoon; Kim, Si-Eun; Kim, Kyoung-Nam; Han, Jeon-Geon; Boonyawan, Dheerawan

2013-10-01

In this study, we focused on sericin hydrolysates, originating from silkworm used in serum-free human bone marrow-derived mesenchymal stem cells (hBM-MSCs) culture. We reported the effect of a covalent linkage between a bioactive protein molecule and polystyrene dish surface via a carbon intermediate layer which can slow down the release rate of protein compounds into the phosphate buffer saline (PBS) solution. Films of amorphous carbon (a-C) and functionalized-carbon were deposited on PS culture dish surfaces by using a DC magnetron sputtering system and RF PECVD system. We found that a-C based-films can increase the hydrophilicity and biocompatibility of polystyrene (PS) dishes, especially a-C films and a-C:N2 films showed good attachment of hBM-MSCs at 24 h. However, in the case of silica surface (a-C:SiOx films), the cells showed a ragged and unattached boundary resulting from the presence of surface silanol groups. For the UV-vis absorbance, all carbon modified-PS dishes showed a lower release rate of sericin molecules into PBS solution than PS control. This revealed that the functionalized carbon could be enhanced by specific binding properties with given molecules. The carbon-coated PS dishes grafting with sericin protein were used in a serum-free condition. We also found that hBM-MSCs have higher percentage of proliferated cells at day 7 for the modified dishes with carbon films and coated with sericin than the PS control coated with sericin. The physical film properties were measured by atomic force microscopy (AFM), scanning electron microscope (SEM) and contact angle measurement. The presence of sbnd NH2 groups of sericin compounds on the PS dish was revealed by Fourier transform infrared spectroscopy (FTIR). The stability of covalent bonds of sericin molecules after washing out ungrafted sericin was confirmed by X-ray photoelectron spectroscopy (XPS).

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.

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

Surface modified and medicated polyurethane materials capable of controlling microorganisms causing foot skin infection in athletes.

PubMed

Gnanasundaram, Saraswathy; Ranganathan, Mohan; Das, Bhabendra Nath; Mandal, Asit Baran

2013-02-01

Foot odor and foot infection are major problems of athletes and persons with hyperhidrosis. Many shoes especially sports shoes have removable cushion insoles/foot beds for foot comfort. Polyurethane (PU) foam and elastomer have been used as cushion insole in shoes. In the present work, new insole materials based on porous viscoelastic PU sheets having hydrophilic property and antimicrobial drug coating to control foot infection and odor were developed. Bacteria and fungus that are causing infection and bad odor of the foot of athletes were isolated by microbial cell culturing of foot sweat. The surface of porous viscoelastic PU sheets was modified using hydrophilic polymers and coated with antimicrobial agent, silver sulfadiazine (SS). The surface modified PU sheets were characterized using ATR-FTIR, TGA, DSC, SEM, contact angle measurement and water absorption study. Results had shown that modified PU sheets have hydrophilicity greater than that of original PU sheet. FTIR spectra and SEM pictures confirmed modification of PU surface with hydrophilic polymers and coating with SS. Minimum inhibitory concentration studies indicated that SS has activity on all isolated bacteria of athletic foot sweat. The maximum inhibition was found for Pseudomonas (20mm) followed by Micrococci (17 mm), Diphtheroids (16 mm) and Staphylococci (12 mm). During perspiration of foot the hydrophilic polymers on PU surface will swell and release SS. Future work will confirm the application of these materials as inserts in athletic shoes. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetically modified organisms: an analysis of the regulatory framework currently employed within the European Union.

PubMed

Gent, R N

1999-09-01

Genetic engineering technology is starting to bring many commercial products to the market. These genetically modified organisms (GMOs) and their derived products are subject to topical debate as to their benefits and risks. The strengths and weaknesses of the regulatory framework that controls their development and application is central to the question of whether this technology poses significant risk to the public health during this critical phase of its evolution. A critical review was carried out of the legal framework regulating the contained use, deliberate release and some aspects of consumer protection relevant to the control of GMOs in Europe and the United Kingdom. The current legal framework is failing to provide a speed of adaptation commensurate with the development of the science of genetic engineering; failing to properly respond to democratic control; failing to resolve significant conflict between the protection of free markets and protection of public health and the environment; and failing to implement obligations on biodiversity. The present legal framework must be replaced. Current European Union proposals for new standards of regulation are welcome, but provide only for further incremental change, and do not address some significant fundamental flaws in our current laws.

Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability.

PubMed

Tao, Sarah L; Desai, Tejal A

2005-12-05

Advances in microelectomechanical systems (MEMS) have allowed the microfabrication of polymeric substrates and the development of a novel class of controlled delivery devices. These vehicles have specifically tailored three-dimensional physical and chemical features which, together, provide the capacity to target cells, promote unidirectional controlled release, and enhance permeation across the intestinal epithelial barrier. Examining the biological response at the microdevice biointerface may provide insight into the benefits of customized surface chemistry and structure in terms of complex drug delivery vehicle design. Therefore, the aim of this work was to determine the interfacial effects of selective surface chemistry and architecture of tomato lectin (TL)-modified poly(methyl methacrylate) (PMMA) drug delivery microdevices on the Caco-2 cell line, a model of the gastrointestinal tract.

Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries

DTIC Science & Technology

2010-07-01

TITLE: Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries PRINCIPAL INVESTIGATOR: David H. Sachs, M.D...4. TITLE AND SUBTITLE Genetically Modified Porcine Skin Grafts for Treatment of 5a. CONTRACT NUMBER Severe Burn Injuries 5b. GRANT NUMBER...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES Burns, skin grafts , genetic

Analytical Method Development and Validation for the Quantification of Acetone and Isopropyl Alcohol in the Tartaric Acid Base Pellets of Dipyridamole Modified Release Capsules by Using Headspace Gas Chromatographic Technique

PubMed Central

2018-01-01

A simple, sensitive, accurate, robust headspace gas chromatographic method was developed for the quantitative determination of acetone and isopropyl alcohol in tartaric acid-based pellets of dipyridamole modified release capsules. The residual solvents acetone and isopropyl alcohol were used in the manufacturing process of the tartaric acid-based pellets of dipyridamole modified release capsules by considering the solubility of the dipyridamole and excipients in the different manufacturing stages. The method was developed and optimized by using fused silica DB-624 (30 m × 0.32 mm × 1.8 µm) column with the flame ionization detector. The method validation was carried out with regard to the guidelines for validation of analytical procedures Q2 demanded by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). All the validation characteristics were meeting the acceptance criteria. Hence, the developed and validated method can be applied for the intended routine analysis. PMID:29686931

Analytical Method Development and Validation for the Quantification of Acetone and Isopropyl Alcohol in the Tartaric Acid Base Pellets of Dipyridamole Modified Release Capsules by Using Headspace Gas Chromatographic Technique.

PubMed

Valavala, Sriram; Seelam, Nareshvarma; Tondepu, Subbaiah; Jagarlapudi, V Shanmukha Kumar; Sundarmurthy, Vivekanandan

2018-01-01

A simple, sensitive, accurate, robust headspace gas chromatographic method was developed for the quantitative determination of acetone and isopropyl alcohol in tartaric acid-based pellets of dipyridamole modified release capsules. The residual solvents acetone and isopropyl alcohol were used in the manufacturing process of the tartaric acid-based pellets of dipyridamole modified release capsules by considering the solubility of the dipyridamole and excipients in the different manufacturing stages. The method was developed and optimized by using fused silica DB-624 (30 m × 0.32 mm × 1.8  µ m) column with the flame ionization detector. The method validation was carried out with regard to the guidelines for validation of analytical procedures Q2 demanded by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). All the validation characteristics were meeting the acceptance criteria. Hence, the developed and validated method can be applied for the intended routine analysis.

Effects of vasoactive intestinal polypeptide on antigen-induced bronchoconstriction and thromboxane release in guinea-pig lung.

PubMed Central

Ciabattoni, G.; Montuschi, P.; Currò, D.; Togna, G.; Preziosi, P.

1993-01-01

1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose-dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/- 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8495242

Plants may alter competition by modifying nutrient bioavailability in rhizosphere: a modeling approach.

PubMed

Raynaud, Xavier; Jaillard, Benoît; Leadley, Paul W

2008-01-01

Plants modify nutrient availability by releasing chemicals in the rhizosphere. This change in availability induced by roots (bioavailability) is known to improve nutrient uptake by individual plants releasing such compounds. Can this bioavailability alter plant competition for nutrients and under what conditions? To address these questions, we have developed a model of nutrient competition between plant species based on mechanistic descriptions of nutrient diffusion, plant exudation, and plant uptake. The model was parameterized using data of the effects of root citrate exudation on phosphorus availability. We performed a sensitivity analysis for key parameters to test the generality of these effects. Our simulations suggest the following. (1) Nutrient uptake depends on the number of roots when nutrients and exudates diffuse little, because individual roots are nearly independent in terms of nutrient supply. In this case, bioavailability profits only species with exudates. (2) Competition for nutrients depends on the spatial arrangement of roots when nutrients diffuse little but exudates diffuse widely. (3) Competition for nutrients depends on the nutrient uptake capacity of roots when nutrients and exudates diffuse widely. In this case, bioavailability profits all species. Mechanisms controlling competition for bioavailable nutrients appear to be diverse and strongly depend on soil, nutrient, and plant properties.

Application of magnesium modified corn biochar for phosphorus removal and recovery from swine wastewater.

PubMed

Fang, Ci; Zhang, Tao; Li, Ping; Jiang, Rong-feng; Wang, Ying-cai

2014-09-05

The recycling of lost phosphorus (P) is important in sustainable development. In line with this objective, biochar adsorption is a promising method of P recovery. Therefore, our study investigates the efficiency and selectivity of magnesium modified corn biochar (Mg/biochar) in relation to P adsorption. It also examines the available P derived from postsorption Mg/biochar. Mg/biochar is rich in magnesium nanoparticles and organic functional groups, and it can adsorb 90% of the equilibrium amount of P within 30 min. The Mg/biochar P adsorption process is mainly controlled by chemical action. The maximum P adsorption amount of Mg/biochar is 239 mg/g. The Langmuir-Freundlich model fits the P adsorption isotherm best. Thermodynamics calculation shows ∆H > 0, ∆G < 0, ∆S > 0, and it demonstrates the P adsorption process is an endothermic, spontaneous, and increasingly disordered. The optimal pH is 9. The amounts of P adsorbed by Mg/B300, Mg/B450, and Mg/B600 from swine wastewater are lower than that adsorbed from synthetic P wastewater by 6.6%, 4.8%, and 4.2%, respectively. Mg/biochar is more resistant to pH and to the influence of coexisting ions than biochar. Finally, postsorption Mg/biochar can release P persistently. The P release equilibrium concentrations are ordered as follows: Mg/B600 > Mg/B450 > Mg/B300. The postsorption Mg/B300, Mg/B450, and Mg/B600 can release 3.3%, 3.9%, and 4.4% of the total adsorbed P, respectively, per interval time.

Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ß production.

PubMed

Bordji, Karim; Becerril-Ortega, Javier; Nicole, Olivier; Buisson, Alain

2010-11-24

Calcium is a key mediator controlling essential neuronal functions depending on electrical activity. Altered neuronal calcium homeostasis affects metabolism of amyloid precursor protein (APP), leading to increased production of β-amyloid (Aβ), and contributing to the initiation of Alzheimer's disease (AD). A linkage between excessive glutamate receptor activation and neuronal Aβ release was established, and recent reports suggest that synaptic and extrasynaptic NMDA receptor (NMDAR) activation may have distinct consequences in plasticity, gene regulation, and neuronal death. Here, we report for the first time that prolonged activation of extrasynaptic NMDAR, but not synaptic NMDAR, dramatically increased the neuronal production of Aβ. This effect was preceded by a shift from APP695 to Kunitz protease inhibitory domain (KPI) containing APPs (KPI-APPs), isoforms exhibiting an important amyloidogenic potential. Conversely, after synaptic NMDAR activation, we failed to detect any KPI-APP expression and neuronal Aβ production was not modified. Calcium imaging data showed that intracellular calcium concentration after extrasynaptic NMDAR stimulation was lower than after synaptic activation. This suggests distinct signaling pathways for each pool of receptors. We found that modification of neuronal APP expression pattern triggered by extrasynaptic NMDAR activation was regulated at an alternative splicing level involving calcium-/calmodulin-dependent protein kinase IV, but overall APP expression remained identical. Finally, memantine dose-dependently inhibited extrasynaptic NMDAR-induced KPI-APPs expression as well as neuronal Aβ release. Altogether, these data suggest that a chronic activation of extrasynaptic NMDAR promotes amyloidogenic KPI-APP expression leading to neuronal Aβ release, representing a causal risk factor for developing AD.

Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan.

PubMed

Biswas, Nikhil

2017-03-01

The aim was to improve the oral bioavailability and antihypertensive activity of poorly soluble drug valsartan (VAL) by modifying the design and delivery of mesoporous silica nanoparticles (MSNs). The synthesized MSNs were functionalized with aminopropyl groups (AP-MSN) through postsynthesis and coated with pH sensitive polymer Eudragit L100-55 (AP-MSN-L100-55) for pH dependant sustain release of anionic VAL. MSNs were characterized by Brauner-Emmett-Teller (BET) surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope (FESEM), Powder X-Ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC). Functionalized MSNs showed highest entrapment efficiency (59.77%) due to strong ionic interaction with VAL. In vitro dissolution of M-MSN [MSN-VAL and AP-MSN-VAL-L100-55 mixed equally] at physiological conditions demonstrated immediate release (MSN-VAL fraction) followed by sustained release (AP-MSN-VAL-L100-55 fraction) of 96% VAL in 960min. The dramatic improvement in dissolution was attributed to the amorphization of crystalline VAL by MSNs as evidenced by DSC and PXRD studies. No noticeable cytotoxicity was observed for MSN, AP-MSN and AP-MSN-L100-55 in MTT assay. Pharmacokinetic study of M-MSN confirmed 1.82 fold increases in bioavailability compared to commercial Diovan tablet in fasted male rabbits. Blood pressure monitoring in rats showed that the morning dosing of Diovan tablet efficiently controlled BP for just over 360min whereas the effect of M-MSN lasted for >840min. Copyright © 2016 Elsevier B.V. All rights reserved.

Modification of the surfaces of medical devices to prevent microbial adhesion and biofilm formation.

PubMed

Desrousseaux, C; Sautou, V; Descamps, S; Traoré, O

2013-10-01

The development of devices with surfaces that have an effect against microbial adhesion or viability is a promising approach to the prevention of device-related infections. To review the strategies used to design devices with surfaces able to limit microbial adhesion and/or growth. A PubMed search of the published literature. One strategy is to design medical devices with a biocidal agent. Biocides can be incorporated into the materials or coated or covalently bonded, resulting either in release of the biocide or in contact killing without release of the biocide. The use of biocides in medical devices is debated because of the risk of bacterial resistance and potential toxicity. Another strategy is to modify the chemical or physical surface properties of the materials to prevent microbial adhesion, a complex phenomenon that also depends directly on microbial biological structure and the environment. Anti-adhesive chemical surface modifications mostly target the hydrophobicity features of the materials. Topographical modifications are focused on roughness and nanostructures, whose size and spatial organization are controlled. The most effective physical parameters to reduce bacterial adhesion remain to be determined and could depend on shape and other bacterial characteristics. A prevention strategy based on reducing microbial attachment rather than on releasing a biocide is promising. Evidence of the clinical efficacy of these surface-modified devices is lacking. Additional studies are needed to determine which physical features have the greatest potential for reducing adhesion and to assess the usefulness of antimicrobial coatings other than antibiotics. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Doxycycline-containing glass ionomer cement for arresting residual caries: an in vitro study and a pilot trial.

PubMed

Castilho, Aline Rogéria Freire de; Duque, Cristiane; Kreling, Paula Fernanda; Pereira, Jesse Augusto; Paula, Andreia Bolzan de; Sinhoreti, Mario Alexandre Coelho; Puppin-Rontani, Regina Maria

2018-01-01

In a previous study, we demonstrated that the incorporation of doxycycline hyclate (DOX) into resin-modified glass ionomer cement (RMGIC) inhibited important cariogenic microorganisms, without modifying its biological and mechanical characteristics. In this study, we keep focused on the effect of that experimental material as a potential therapy for arresting residual caries by analyzing other in vitro properties and conducting a pilot clinical trial assessing the in vivo effect of DOX-containing RMGIC on residual mutans streptococci after partial carious removal in primary molars. Specimens of the groups RMGIC (control); RMGIC + 1.5% DOX; RMGIC + 3% DOX; and RMGIC + 4.5% DOX were made to evaluate the effect of DOX incorporation on surface microhardness and fluoride release of RMGIC and against biofilm of Streptococcus mutans. Clinical intervention consisted of partial caries removal comparing RMGIC and RMGIC + 4.5% DOX as lining materials. After 3 months, clinical and microbiologic evaluations were performed. Data were submitted to ANOVA/Tukey or Wilcoxon/Mann-Whitney set as α=0.05. Fluoride release and surface microhardness was not influenced by the incorporation of DOX (p>0.05). There was a significant reduction of S. mutans biofilm over the material surface with the increase of DOX concentration. After clinical trial, the remaining dentin was hard and dry. Additionally, mutans streptococci were completely eliminated after 3 months of treatment with RMGIC + 4.5% DOX. The incorporation of DOX provided better antibiofilm effect, without jeopardizing fluoride release and surface microhardness of RMGIC. This combination also improved the in vivo shortterm microbiological effect of RMGIC after partial caries removal.

Application of Magnesium Modified Corn Biochar for Phosphorus Removal and Recovery from Swine Wastewater

PubMed Central

Fang, Ci; Zhang, Tao; Li, Ping; Jiang, Rong-feng; Wang, Ying-cai

2014-01-01

The recycling of lost phosphorus (P) is important in sustainable development. In line with this objective, biochar adsorption is a promising method of P recovery. Therefore, our study investigates the efficiency and selectivity of magnesium modified corn biochar (Mg/biochar) in relation to P adsorption. It also examines the available P derived from postsorption Mg/biochar. Mg/biochar is rich in magnesium nanoparticles and organic functional groups, and it can adsorb 90% of the equilibrium amount of P within 30 min. The Mg/biochar P adsorption process is mainly controlled by chemical action. The maximum P adsorption amount of Mg/biochar is 239 mg/g. The Langmuir-Freundlich model fits the P adsorption isotherm best. Thermodynamics calculation shows ∆H > 0, ∆G < 0, ∆S > 0, and it demonstrates the P adsorption process is an endothermic, spontaneous, and increasingly disordered. The optimal pH is 9. The amounts of P adsorbed by Mg/B300, Mg/B450, and Mg/B600 from swine wastewater are lower than that adsorbed from synthetic P wastewater by 6.6%, 4.8%, and 4.2%, respectively. Mg/biochar is more resistant to pH and to the influence of coexisting ions than biochar. Finally, postsorption Mg/biochar can release P persistently. The P release equilibrium concentrations are ordered as follows: Mg/B600 > Mg/B450 > Mg/B300. The postsorption Mg/B300, Mg/B450, and Mg/B600 can release 3.3%, 3.9%, and 4.4% of the total adsorbed P, respectively, per interval time. PMID:25198685

Instructions to "push as hard as you can" improve average chest compression depth in dispatcher-assisted cardiopulmonary resuscitation.

PubMed

Mirza, Muzna; Brown, Todd B; Saini, Devashish; Pepper, Tracy L; Nandigam, Hari Krishna; Kaza, Niroop; Cofield, Stacey S

2008-10-01

Cardiopulmonary resuscitation (CPR) with adequate chest compression depth appears to improve first shock success in cardiac arrest. We evaluate the effect of simplification of chest compression instructions on compression depth in dispatcher-assisted CPR protocol. Data from two randomized, double-blinded, controlled trials with identical methodology were combined to obtain 332 records for this analysis. Subjects were randomized to either modified Medical Priority Dispatch System (MPDS) v11.2 protocol or a new simplified protocol. The main difference between the protocols was the instruction to "push as hard as you can" in the simplified protocol, compared to "push down firmly 2in. (5cm)" in MPDS. Data were recorded via a Laerdal ResusciAnne SkillReporter manikin. Primary outcome measures included: chest compression depth, proportion of compressions without error, with adequate depth and with total release. Instructions to "push as hard as you can", compared to "push down firmly 2in. (5cm)", resulted in improved chest compression depth (36.4 mm vs. 29.7 mm, p<0.0001), and improved median proportion of chest compressions done to the correct depth (32% vs. <1%, p<0.0001). No significant difference in median proportion of compressions with total release (100% for both) and average compression rate (99.7 min(-1) vs. 97.5 min(-1), p<0.56) was found. Modifying dispatcher-assisted CPR instructions by changing "push down firmly 2in. (5cm)" to "push as hard as you can" achieved improvement in chest compression depth at no cost to total release or average chest compression rate.

Gelatin modified lipid nanoparticles for anti- viral drug delivery.

PubMed

K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

2017-10-01

The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Layered Metal Nanoparticle Structures on Electrodes for Sensing, Switchable Controlled Uptake/Release, and Photo-electrochemical Applications.

PubMed

Tel-Vered, Ran; Kahn, Jason S; Willner, Itamar

2016-01-06

Layered metal nanoparticle (NP) assemblies provide highly porous and conductive composites of unique electrical and optical (plasmonic) properties. Two methods to construct layered metal NP matrices are described, and these include the layer-by-layer deposition of NPs, or the electropolymerization of monolayer-functionalized NPs, specifically thioaniline-modified metal NPs. The layered NP composites are used as sensing matrices through the use of electrochemistry or surface plasmon resonance (SPR) as transduction signals. The crosslinking of the metal NP composites with molecular receptors, or the imprinting of molecular recognition sites into the electropolymerized NP matrices lead to selective and chiroselective sensing interfaces. Furthermore, the electrosynthesis of redox-active, imprinted, bis-aniline bridged Au NP composites yields electrochemically triggered "sponges" for the switchable uptake and release of electron-acceptor substrates, and results in conductive surfaces of electrochemically controlled wettability. Also, photosensitizer-relay-crosslinked Au NP composites, or electrochemically polymerized layered semiconductor quantum dot/metal NP matrices on electrodes, are demonstrated as functional nanostructures for photoelectrochemical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of complex internal structures on rheology of multiple emulsions particles in 2D from a boundary integral method.

PubMed

Wang, Jingtao; Liu, Jinxia; Han, Junjie; Guan, Jing

2013-02-08

A boundary integral method is developed to investigate the effects of inner droplets and asymmetry of internal structures on rheology of two-dimensional multiple emulsion particles with arbitrary numbers of layers and droplets within each layer. Under a modest extensional flow, the number increment of layers and inner droplets, and the collision among inner droplets subject the particle to stronger shears. In addition, the coalescence or release of inner droplets changes the internal structure of the multiple emulsion particles. Since the rheology of such particles is sensitive to internal structures and their change, modeling them as the core-shell particles to obtain the viscosity equation of a single particle should be modified by introducing the time-dependable volume fraction Φ(t) of the core instead of the fixed Φ. An asymmetric internal structure induces an oriented contact and merging of the outer and inner interface. The start time of the interface merging is controlled by adjusting the viscosity ratio and enhancing the asymmetry, which is promising in the controlled release of inner droplets through hydrodynamics for targeted drug delivery.

Control of heat transfer in continuous-feeding Czochralski-silicon crystal growth with a water-cooled jacket

NASA Astrophysics Data System (ADS)

Zhao, Wenhan; Liu, Lijun

2017-01-01

The continuous-feeding Czochralski method is an effective method to reduce the cost of single crystal silicon. By promoting the crystal growth rate, the cost can be reduced further. However, more latent heat will be released at the melt-crystal interface under a high crystal growth rate. In this study, a water-cooled jacket was applied to enhance the heat transfer at the melt-crystal interface. Quasi-steady-state numerical calculation was employed to investigate the impact of the water-cooled jacket on the heat transfer at the melt-crystal interface. Latent heat released during the crystal growth process at the melt-crystal interface and absorbed during feedstock melting at the feeding zone was modeled in the simulations. The results show that, by using the water-cooled jacket, heat transfer in the growing crystal is enhanced significantly. Melt-crystal interface deflection and thermal stress increase simultaneously due to the increase of radial temperature at the melt-crystal interface. With a modified heat shield design, heat transfer at the melt-crystal interface is well controlled. The crystal growth rate can be increased by 20%.

Controlled release of modified insulin glargine from novel biodegradable injectable gels.

PubMed

Anand, Om; Almoazen, Hassan; Mehrotra, Nitin; Johnson, James; Shukla, Atul

2012-03-01

The objective of this study was to investigate the duration of biological effects of modified insulin glargine released from a novel biodegradable injectable gel in type II diabetic Zucker diabetic fatty (ZDF) rats. Modified insulin glargine was purified from the marketed formulation by process of dialysis followed by freeze-drying, and the purity was confirmed by the single peak, corresponding to insulin glargine in the HPLC chromatogram. To determine and to compare the biological activity of purified insulin glargine with marketed formulation, it was suspended in isotonic saline solutions and administered subcutaneously to ZDF rats at a dose of 10 IU/kg of insulin and the blood glucose levels were measured. The blood glucose levels of ZDF rats after a subcutaneous injection of a suspension of purified insulin glargine decreased below 200 mg/dL within 2 h and remained at this level up to 6 h, then steadily raised above 400 mg/dL in 12 h. Insulin glargine particles were loaded into a novel biodegradable injectable gel formulation prepared from a blend of polylactic-co-glycolic acid (PLGA) and biocompatible plasticizers. Approximately 0.1 mL of insulin glargine-loaded gel prepared with PLGA was administered subcutaneously to the ZDF rats, and blood glucose levels were measured. The PLGA gel formulations prepared with insulin glargine particles had duration of action of 10 days following a single subcutaneous injection. The addition of zinc sulfate to the formulations prepared with purified insulin glargine particles further slowed down the drop in blood glucose concentrations.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation.

PubMed

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-02-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40-60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs-Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

[Leptin: aspects on energetic balance, physical exercise and athletic amenorhea].

PubMed

Ribeiro, Sandra Maria Lima; dos Santos, Zirlene Adriana; da Silva, Renata Juliana; Louzada, Eliana; Donato, José; Tirapegui, Julio

2007-02-01

The aim of this manuscript was to review the knowledge about leptin, detailing its relationship with energetic intake and physical activity. Leptin is an adipocyte hormone, recognized mainly for its putative role in control of energy expenditure, food intake, body weight and reproductive function. Leptin has still important peripheral actions, including its role on the ovarian tissue. The intracellular signaling mechanisms are recognized in hypothalamus, but in peripheral tissue are not fully understood. The exercise, when practiced by women, if not appropriately planned according to food intake, can modify the leptin release. When energy imbalances induced by exercise and/or deficient food ingestion occurs, low leptin levels are observed, leading to a reduction in GnRH (gonadotropin-release hormone), in LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in pituitary, and consequently a minor release of ovarian estrogens. This process is named hypothalamic amenorrhea, and has repercussions in the woman's health. In this perspective, it is important to emphasize the need to evaluate the energy expenditure from exercise and to formulate adequate alimentary plans to these individuals.

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

PubMed

Zhang, Yuanyuan; Ang, Chung Yen; Li, Menghuan; Tan, Si Yu; Qu, Qiuyu; Luo, Zhong; Zhao, Yanli

2015-08-19

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation

PubMed Central

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-01-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40–60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs–Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL. PMID:18197871

A novel bio electro active alginate-aniline tetramer/ agarose scaffold for tissue engineering: synthesis, characterization, drug release and cell culture study.

PubMed

Atoufi, Zhale; Zarrintaj, Payam; Motlagh, Ghodratollah Hashemi; Amiri, Anahita; Bagher, Zohreh; Kamrava, Seyed Kamran

2017-10-01

In this study, synthesis of a novel biocompatible stimuli-responsive conducting hydrogel based on agarose/alginate-aniline tetramer with the capability of a tailored electrically controlled drug-release for neuroregeneration is investigated. First, aniline tetramer is synthesized and grafted onto sodium alginate. Then, this material is added to agarose as an electrical conductivity modifier to obtain Agarose/alginate-aniline tetramer hydrogel. The synthesized materials are characterized by H NMR and FTIR. The hydrogels are prepared with varying content of aniline tetramer and their swelling-deswelling and shape memory behavior is evaluated. The electroactivity and ionic conductivity of hydrogels against temperature is measured. The sample with 10% aniline tetramer (AT10) reveals the highest ionic conductivity. In MTT and SEM assays, AT10 shows the best cell viability and cell proliferation due to its highest ionic conductivity highlighting the fact that electrical stimuli cell signaling. Hydrogels also represent great potentials for passive and electro-stimulated dexamethasone release. These results demonstrate that the newly developed conducting hydrogels are promising materials for neuroregenerative medicine.

Design and characterisation of a polyethylene oxide matrix with the potential use as a teat insert for prevention/treatment of bovine mastitis.

PubMed

Bhattarai, Sushila; Alany, Raid G; Bunt, Craig R; Abdelkader, Hamdy; Rathbone, Michael J

2015-01-01

This manuscript reports (for the first time) on antibiotic-free polymeric inserts for the prevention and/or treatment of bovine mastitis. Polyethylene oxide (PEO)-based inserts were prepared using different concentrations of various hydrophilic polymers and water-soluble and water-insoluble drug-release-modifying excipients. A simple and scalable melt-extrusion method was employed to prepare the inserts. The prepared inserts were characterised for their dimension, rheological and mechanical properties. The in vitro release of a model bacteriostatic drug (salicylic acid) from the prepared inserts was studied to demonstrate the effectiveness and reproducibility of the melt-extrusion manufacturing method. Further, the in vitro stability of the inserts was evaluated using gel permeation chromatography (GPC) to monitor any change in molecular weight under real-time and accelerated storage conditions. The investigated inserts were stable at accelerated storage conditions over a period of 6 months. PEO inserts have the potential to serve a dual purpose, act as a physical barrier against pathogens invading the teat canal of cows and possibly control the release of a drug.

Killing bacteria within biofilms by sustained release of tetracycline from triple-layered electrospun micro/nanofibre matrices of polycaprolactone and poly(ethylene-co-vinyl acetate).

PubMed

Alhusein, Nour; De Bank, Paul A; Blagbrough, Ian S; Bolhuis, Albert

2013-12-01

We report the controlled release of the antibiotic tetracycline (tet) HCl from a triple-layered electrospun matrix consisting of a central layer of poly(ethylene-co-vinyl acetate (PEVA) sandwiched between outer layers of poly-ε-caprolactone (PCL). These micro/nanofibre layers with tet successfully encapsulated (essentially quantitatively at 3 and 5 % w/w) in each layer, efficiently inhibited the growth of a panel of bacteria, including clinical isolates, as shown by a modified Kirby-Bauer disc assay. Furthermore, they demonstrated high biological activity in increasingly complex models of biofilm formation (models that are moving closer to the situation in a wound) by stopping biofilm formation, by killing preformed biofilms and killing mature, dense biofilm colonies of Staphylococcus aureus MRSA252. Tet is clinically useful with potential applications in wound healing and especially in complicated skin and skin-structure infections; electrospinning provides good encapsulation efficiency of tet within PCL/PEVA/PCL polymers in micro/nanofibre layers which display sustained antibiotic release in formulations that are anti-biofilm.

Characteristics of platelet gels combined with silk

PubMed Central

Pallotta, Isabella; Kluge, Jonathan A.; Moreau, Jodie; Calabrese, Rossella

2014-01-01

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact. PMID:24480538

Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

PubMed

Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

2014-08-01

Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

Temperature Jump Pyrolysis Studies of RP 2 Fuel

DTIC Science & Technology

2017-01-09

Release; Distribution Unlimited. The U.S. Government is joint author of the work and has the right to use, modify , reproduce, release, perform...Mixture RP-2 is a real fuel consisting of hundreds of different compounds; comprised primarily of kerosene There is little sulfur containing

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design.

PubMed

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X(1)), surfactant (X(2)), and drug/lipid ratio (X(3)) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was -8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas-Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.

Hydrophobin-nanofibrillated cellulose stabilized emulsions for encapsulation and release of BCS class II drugs.

PubMed

Paukkonen, Heli; Ukkonen, Anni; Szilvay, Geza; Yliperttula, Marjo; Laaksonen, Timo

2017-03-30

The purpose of this study was to construct biopolymer-based oil-in-water emulsion formulations for encapsulation and release of poorly water soluble model compounds naproxen and ibuprofen. Class II hydrophobin protein HFBII from Trichoderma reesei was used as a surfactant to stabilize the oil/water interfaces of the emulsion droplets in the continuous aqueous phase. Nanofibrillated cellulose (NFC) was used as a viscosity modifier to further stabilize the emulsions and encapsulate protein coated oil droplets in NFC fiber network. The potential of both native and oxidized NFC were studied for this purpose. Various emulsion formulations were prepared and the abilities of different formulations to control the drug release rate of naproxen and ibuprofen, used as model compounds, were evaluated. The optimal formulation for sustained drug release consisted of 0.01% of drug, 0.1% HFBII, 0.15% oxidized NFC, 10% soybean oil and 90% water phase. By comparison, the use of native NFC in combination with HFBII resulted in an immediate drug release for both of the compounds. The results indicate that these NFC originated biopolymers are suitable for pharmaceutical emulsion formulations. The native and oxidized NFC grades can be used as emulsion stabilizers in sustained and immediate drug release applications. Furthermore, stabilization of the emulsions was achieved with low concentrations of both HFBII and NFC, which may be an advantage when compared to surfactant concentrations of conventional excipients traditionally used in pharmaceutical emulsion formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles.

PubMed

Thauvin, Cédric; Schwarz, Bettina; Delie, Florence; Allémann, Eric

2017-11-15

Advantages associated with the use of polylactic acid (PLA) nano- or microparticles as drug delivery systems have been widely proven in the field of pharmaceutical sciences. These biodegradable and biocompatible carriers have demonstrated different loading and release properties depending on interactions with the cargo, preparation methods, particles size or molecular weight of PLA. In this study, we sought to show the possibility of influencing these properties by modifying the structure of the constituting polymer. Seven non-functionalized or functionalized PLA polymers were specifically designed and synthesized by microwave-assisted ring-opening polymerization of d,l-lactide. They presented short hydrophobic and/or hydrophilic groups thanks to the use of C20 aliphatic chain, mPEG1000, sorbitan esters (Spans ® ) or polysorbates (Tweens ® ), their PEGylated analogues, as initiators. Then, seven types of drug-loaded nanoparticles (NP) were prepared from these polymers and compared in terms of physico-chemical characteristics, drug loading and release profiles. Although the loading properties were not improved with any of the functionalized PLA NP, different release profiles were observed in an aqueous medium at 37 °C and over a period of five days. The presence of PEG moieties in the core of PLA-polysorbates NP induced a faster release while the addition of a single aliphatic chain induced a slower release due to better interactions with the active molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

PubMed Central

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X1), surfactant (X2), and drug/lipid ratio (X3) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was −8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release. PMID:21556343

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

PubMed

Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

2017-12-01

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes.

PubMed

Vianna, Andre Gustavo Daher; Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Faria-Neto, Jose Rocha

2018-05-01

This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks. In total, 42 patients (age: 61.9 ± 5.9 years, baseline glycated hemoglobin (HbA1c): 7.3 ± 0.56) were selected and 37 completed the 24-week protocol. Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference between the groups did not reach statistical significance. Vildagliptin also significantly decreased the standard deviation of the mean glucose (SD) and the mean of the daily differences (MODD) (p = 0.007 and 0.030). Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM after 24 weeks of treatment. Further studies are required to attest differences between vildagliptin and gliclazide MR regarding glycemic variability. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of the suitability of GOCE-based geoid models for the unification of the North American vertical datums

NASA Astrophysics Data System (ADS)

Amjadiparvar, Babak; Sideris, Michael

2015-04-01

Precise gravimetric geoid heights are required when the unification of vertical datums is performed using the Geodetic Boundary Value Problem (GBVP) approach. Five generations of Global Geopotential Models (GGMs) derived from Gravity field and steady-state Ocean Circulation Explorer (GOCE) observations have been computed and released so far (available via IAG's International Centre for Global Earth Models, ICGEM, http://icgem.gfz-potsdam.de/ICGEM/). The performance of many of these models with respect to geoid determination has been studied in order to select the best performing model to be used in height datum unification in North America. More specifically, Release-3, 4 and 5 of the GOCE-based global geopotential models have been evaluated using GNSS-levelling data as independent control values. Comparisons against EGM2008 show that each successive release improves upon the previous one, with Release-5 models showing an improvement over EGM2008 in Canada and CONUS between spherical harmonic degrees 100 and 210. In Alaska and Mexico, a considerable improvement over EGM2008 was brought by the Release-5 models when used up to spherical harmonic degrees of 250 and 280, respectively. The positive impact of the Release-5 models was also felt when a gravimetric geoid was computed using the GOCE-based GGMs together with gravity and topography data in Canada. This geoid model, with appropriately modified Stokes kernel between spherical harmonic degrees 190 and 260, performed better than the official Canadian gravimetric geoid model CGG2013, thus illustrating the advantages of using the latest release GOCE-based models for vertical datum unification in North America.

[Controlled release of prednisolone from suppository prepared using powder of pulverized tablet].

PubMed

Tatsumi, Akitoshi; Oda, Shoko; Nakamoto, Tomoko; Muraoka, Reiko; Takahashi, Yoshiko; Tanaka, Kuniyoshi; Shikata, Toshiyuki; Tatsumi, Sumiyo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hamaguchi, Tsuneo; Kadobayashi, Muneo

2008-04-01

Prednisolone suppositories have been used successfully for the treatment of ulcerative colitis in hospital settings. However, the raw material of prednisolone suppository, JP prednisolone powder (JP Powder), was recently removed from the market. Therefore we studied the effects of raw material and suppository base on the release of prednisolone suppository for the purpose of designing a new suppository with similar effects to those of suppository prepared using JP powder (old suppository). New suppositories consisting of the powder of pulverized tablet as raw material and Witepsol H-15 and Witepsol E-75 as suppository base were prepared according to the fusion method. Suppository release test was performed by reciprocating dialysis tube method with tapping (RDT method) and dialysis tubing method (DT method). Both RDT method and DT method were performed using a suppository dissolution apparatus (modified JP disintegration apparatus) and a JP15 paddle apparatus, respectively. The test fluid was 50 mM phosphate buffer solution (pH 7.4) maintained at 37+/-0.5 degrees C. The results of release test by RDT method were similar to those of DT method. Release rate of prednisolone from the new suppository was much faster than that of old suppository. The addition of Witepsol E-75 to new suppository base markedly delayed the release of prednisolone from the new suppository. Release rate of prednisolone from the new suppository, consisting of pulverized tablet and Witepsol H-15 and Witepsol E-75 (76:24), corresponded well with that of the old suppository. It was suggested that this suppository could be used as incoming preparation of suppository prepared using JP powder.

Hollow microspheres based on - Folic acid modified - Hydroxypropyl Cellulose and synthetic multi-responsive bio-copolymer for targeted cancer therapy: controlled release of daunorubicin, in vitro and in vivo studies.

PubMed

Metaxa, Aikaterini-Foteini; Efthimiadou, Eleni K; Boukos, Nikos; Fragogeorgi, Eirini A; Loudos, George; Kordas, George

2014-12-01

Conventional chemotherapy drugs such as anthracyclines show no specific activity. They destroy cancer cells but also and the healthy ones, and for that reason exhibit high toxicity. In order to alleviate the toxic effects of chemotherapeutic drugs, the administration dose is being minimized, while their reactivity against tumor cells is lessened. This problem can be overcome or at least reduced by using nanoscale drug delivery systems to target the pathogenic area. The present work deals with the synthesis, characterization and biological evaluation of multi-responsive hollow microspheres coated with Hydroxypropyl Cellulose (HPC)-a biocompatible and thermosensitive polysaccharide-conjugated with folic acid as well promising drug vehicles for targeted cancer therapy. The synthetic route consists of two steps. In the first step, a single layer of sensitive copolymers is ((Methacrylic acid (MAA), N-(2-Hydroxypropyl) methacrylamide (HPMA) and N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(2-methylacrylamide) (DSBMA)) fabricated on a sacrificial template of SiO2 and in the second step, an additional layer of the folic acid modified HPC coat the microspheres' surface. The layers fabrication is performed through a combination of distillation precipitation co-polymerization and chemical deposition method. The loading capacity (% LC) and encapsulation efficiency (% EE) percentages of the chemotherapeutic agent daunorubicin (DNR) in the fabricated microspheres were calculated through the standard curve methodology. In addition, the releasing properties of the resulting spheres are investigated, using the above mentioned methodology. It is worth mentioning that, spheres release the entrapped drug under combined conditions such acidic and reductive environment along with conventional hyperthermia. Cytotoxic activity of the synthesized spheres was investigated by using the well-established method of MTT assay in MCF-7 (breast cancer), HeLa (cervical cancer) and HEK 293 (Human Embryonic Kidney healthy cells) cell lines. Confocal and fluorescence microscopy were used to confirm the in vitro targeted ability of folic acid modified drug loaded microspheres in HeLa, to that overexpress folate receptors, MCF-7 and 3T3 cells, as negative folate cell substrate. Finally, radiolabelling of the spheres is performed, with a gamma emitting radionuclide ((99m)Tc), to assess their in vivo profile by means of scintigraphic imaging and biodistribution studies. Hollow spheres release the encapsulated drug under acidic environment, conventional hyperthermia or in the presence of glutathione (reductive environment). The ability of modified drug carriers to target the HeLa cells, was confirmed by confocal and fluorescence microscopy. The resulting spheres are observed to be promising drug-carriers for cancer treatment due to their releasing properties under tumor's environment and high concentration in HeLa cells via endocytosis. In addition, the empty vehicles have no toxicity in healthy cells and present antimicrobial activity. Copyright © 2014 Elsevier Inc. All rights reserved.

A poly (lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate promoting osteoblast attachment, proliferation and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2014-12-10

We explored a novel biodegradable poly (lactide-co-glycolide) (PLGA) film loaded with over 80 wt% bone morphogenetic protein (BMP-2), which was regarded as a substrate promoting osteoblast attachment, proliferation and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity respectively. The in-vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) controlling. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. This article is protected by copyright. All rights reserved. Copyright © 2014 Wiley Periodicals, Inc., A Wiley Company.

A poly(lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate-promoting osteoblast attachment, proliferation, and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2015-08-01

We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a substrate-promoting osteoblast attachment, proliferation, and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity, respectively. The in vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation, and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. © 2015 Wiley Periodicals, Inc.

Antishear Stress Bionic Carbon Nanotube Mesh Coating with Intracellular Controlled Drug Delivery Constructing Small-Diameter Tissue-Engineered Vascular Grafts.

PubMed

Ding, Ning; Dou, Ce; Wang, Yuxin; Liu, Feila; Guan, Ge; Huo, Da; Li, Yanzhao; Yang, Jingyuan; Wei, Keyu; Yang, Mingcan; Tan, Ju; Zeng, Wen; Zhu, Chuhong

2018-06-01

Small-diameter (<6 mm) tissue-engineered blood vessels (TEBVs) have a low patency rate due to chronic inflammation mediated intimal hyperplasia. Functional coating with drug release is a promising solution, but preventing the released drug from being rushed away by blood flow remains a great challenge. A single-walled carboxylic acid functionalized carbon nanotube (C-SWCNT) is used to build an irregular mesh for TEBV coating. However, an interaction between the released drug and the cells is still insufficient due to the blood flow. Thus, an intracellular drug delivery system mediated by macrophage cellular uptake is designed. Resveratrol (RSV) modified CNT is used for macrophage uptake. M1 macrophage uptakes CNT-RSV and then converts to the M2 phenotype upon intracellular RSV release. Prohealing M2 macrophage inhibits the chronic inflammation thus maintains the contractile phenotype of the vascular smooth muscle cell (VSMC), which reduces intimal hyperplasia. Additionally, RSV released from the mesh coating also directly protects the contractile VSMCs from being converted to a secretory phenotype. Through antishear stress coating and macrophage-based intracellular drug delivery, CNT-RSV TEBVs exhibit a long-term anti-intimal hyperplasia function. Animal transplantation studies show that the patency rate remains high until day 90 after grafting in rat carotid arteries. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes

PubMed Central

Koh, Ahyeon; Riccio, Daniel A.; Sun, Bin; Carpenter, Alexis W.; Nichols, Scott P.; Schoenfisch, Mark H.

2011-01-01

Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance. PMID:21795038

Enhanced cellular transport and drug targeting using dendritic nanostructures

NASA Astrophysics Data System (ADS)

Kannan, R. M.; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

2003-03-01

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. The large density of end groups can also be tailored to create enhanced affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, drug/ligand conjugation, in vitro cellular and in vivo drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Results on PAMAM dendrimers and polyol hyperbranched polymers suggest that: (1) These materials complex/encapsulate a large number of drug molecules and release them at tailorable rates; (2) The drug-dendrimer complex is transported very rapidly through a A549 lung epithelial cancel cell line, compared to free drug, perhaps by endocytosis. The ability of the drug-dendrimer-ligand complexes to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

Preparation and evaluation of metoprolol tartrate sustained-release pellets using hot melt extrusion combined with hot melt coating.

PubMed

Yang, Yan; Shen, Lian; Li, Juan; Shan, Wei-Guang

2017-06-01

The objective of this study was to prepare and evaluate metoprolol tartrate sustained-release pellets. Cores were prepared by hot melt extrusion and coated pellets were prepared by hot melt coating. Cores were found to exist in a single-phase state and drug in amorphous form. Plasticizers had a significant effect on torque and drug content, while release modifiers and coating level significantly affected the drug-release behavior. The mechanisms of drug release from cores and coated pellets were Fickian diffusion and diffusion-erosion. The coated pellets exhibited sustained-release properties in vitro and in vivo.

Use of MODIS Satellite Images and an Atmospheric Dust Transport Model to Evaluate Juniperus spp. Pollen Phenology and Dispersal

NASA Technical Reports Server (NTRS)

Luvall, J. C.; Sprigg, W. A.; Levetin, E.; Huete, A.; Nickovic, S.; Pejanovic, G. A.; Vukovic, A.; VandeWater, P. K.; Myers, O. B.; Budge, A. M.;

You Can Run, But You Can't Hide Juniper Pollen Phenology and Dispersal

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.

2013-01-01

Pollen can be transported great distances. Van de Water et. al., 2003 reported Juniperus spp. pollen was transported 200-600 km. Hence local observations of plant phenology may not be consistent with the timing and source of pollen collected by pollen sampling instruments. The DREAM (Dust REgional Atmospheric Model, Nickovic et al. 2001) is a verified model for atmospheric dust transport modeling using MODIS data products to identify source regions and quantities of dust. We are modified the DREAM model to incorporate pollen transport. Pollen release is estimated based on MODIS derived phenology of Juniperus spp. communities. Ground based observational records of pollen release timing and quantities are used as verification. This information will be used to support the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program and the State of New Mexico environmental public health decision support for asthma and allergies alerts.

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

PubMed

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

40 CFR 372.20 - Process for modifying covered chemicals and facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chemicals and facilities. 372.20 Section 372.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Reporting Requirements § 372.20 Process for modifying covered chemicals...

Controlled release of D-glucose from starch granules containing 29% free D-glucose and Eudragit L100-55 as a binding and coating agent.

PubMed

Kim, Yeon-Kye; Mukerjea, Rupendra; Robyt, John F

2010-05-27

Waxy maize starch (100% amylopectin) granules were modified by reaction of the granules with glucoamylase in a minimum amount of water to give 29% (w/w) D-glucose inside the granules [Kim, Y.-K.; Robyt, J. F. Carbohydr. Res.1999, 318, 129-134]. These granules were made into beads by dropping an ethanol slurry of starch and different amounts of Eudragit L100-55 in a constant ratio of 100:1 from a pipette onto Whatman 3MM filter paper. The starch beads were air dried and then repeatedly sprayed 0-12 times with 2.0% (w/v) Eudragit L100-55 in ethanol, with drying between each spraying, to coat the surface of the starch beads, giving different amounts of Eudragit L100-55 coating. Seven different kinds of beads, with different amounts of Eudragit L100-55 binding and coating agent, were obtained. The rates of release of D-glucose into water from the seven kinds of beads were inversely proportional to the amount of binding and coating agent. Bead type I, which was without any binding and coating gave a fast 100% release of D-glucose in 30 min. Beads II and III also gave a fast 100% release in 60 min and 90 min, respectively. Bead IV gave a near linear release of 97% D-glucose in 150 min; Bead V gave a 50% release in 120 min followed by the remaining 50% in 60 min; and Beads VI and VII gave a slow release of 10% and 4%, respectively, from 0 to 120 min, followed by a rapid 100% release from 120 to 180 min. (c) 2010 Elsevier Ltd. All rights reserved.

Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell

PubMed Central

1985-01-01

A microprocessor-controlled system of microinjections and microaspirations has been developed to change, within approximately 1 ms, the [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils (0.3-0.4 micron radius) of a skinned canine cardiac Purkinje cell (2.5-4.5 micron overall radius) at different phases of a Ca2+ transient. Simultaneously monitoring tension and aequorin bioluminescence provided two methods for estimating the peak myoplasmic [free Ca2+] reached during the spontaneous cyclic Ca2+ release from the SR obtained in the continuous presence of a bulk solution [free Ca2+] sufficiently high to overload the SR. These methods gave results in excellent agreement for the spontaneous Ca2+ release under a variety of conditions of pH and [free Mg2+], and of enhancement of Ca2+ release by calmodulin. Disagreement was observed, however, when the Ca2+ transient was modified during its ascending phase. The experiments also permitted quantification of the aequorin binding within the myofibrils and determination of its operational apparent affinity constant for Ca2+ at various [free Mg2+] levels. An increase of [free Ca2+] at the outer surface of the SR during the ascending phase of the Ca2+ transient induced further release of Ca2+. In contrast, an increase of [free Ca2+] during the descending phase of the Ca2+ transient did not cause further Ca2+ release. Varying [free H+], [free Mg2+], or the [Na+]/[K+] ratio had no significant effect on the Ca2+ transient during which the modification was applied, but it altered the subsequent Ca2+ transient. Therefore, Ca2+ appears to be the major, if not the only, ion controlling Ca2+ release from the SR rapidly enough to alter a Ca2+ transient during its course. PMID:3981128

The current state of the science related to the re-release of mercury from coal combustion products

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

Debra F. Pflughoeft-Hassett; David J. Hassett; Loreal V. Heebink

2006-07-01

The stability of mercury associated with CCPs is an issue that has only recently been under investigation but has become a prominent question as the industry strives to determine if current management options for CCPs will need to be modified. Mercury and other air toxic elements can be present in fly ash, FGD material and bottom ash and boiler slag. Mercury concentrations ranging from {lt} 0.01 to 2.41 ppm in fly ash and from 0.001 to 0.342 ppm in bottom ash have been reported. Stability of mercury must be evaluated by tests that include 1) direct leachability; 2) vapor-phase releasemore » at ambient and elevated temperatures; and 3) microbiologically induced leachability and vapor-phase release. The amount of mercury leached from currently produced CCPs is extremely low and does not appear to represent an environmental or re-release hazard. Concentrations of mercury in leachates from fly ashes and FGD material using either the toxicity characteristic leaching procedure (TCLP) or the synthetic groundwater leaching procedure (SGLP) are generally below detection limits. The release of mercury vapor from CCPs resulting from the use of mercury control technologies has been evaluated on a limited basis. Research indicates that mercury bound to the ash or activated carbon is fairly stable. The EERC found that organomercury species were detected at very low levels both in the vapor and leachate generated from the microbiologically mediated release experiments. The current state of the science indicates that mercury associated with CCPs is stable and highly unlikely to be released under most management conditions, including utilisation and disposal. The exception to this is exposure to high temperatures such as those that may be achieved in cement and wallboard production. Therefore, existing CCPs management options are expected to be environmentally sound options for CCPs from systems with mercury control technologies installed. 2 refs., 2 photos.« less

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

NASA Astrophysics Data System (ADS)

Chen, Cen; Yang, Wei; Wang, Dan-Tong; Chen, Chao-Long; Zhuang, Qing-Ye; Kong, Xiang-Dong

2014-12-01

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug.

PubMed

Huang, Jinheng; Lin, Huaqing; Peng, Bingxin; Huang, Qianfeng; Shuai, Fangzhou; Xie, Yanxian

2018-04-30

The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH 6.8 and pH 1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24 h in acidic media (pH 1.2). The release profile in acidic media was similar to the alkaline media (pH 6.8) with a similarity factor (f 2 ) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.

Native and microwave-modified Terminalia mantaly gums as sustained-release and bioadhesive excipients in naproxen matrix tablet formulations.

PubMed

Odeniyi, Michael Ayodele; Oyedokun, Babatunde Mukhtar; Bamiro, Oluyemisi Adebowale

2017-01-01

Hydrophilic polymers provide a means of sustaining drug delivery. Native gums may be limited in function, but modification may improve their activity. The aim of the study was to evaluate native and modified forms of Terminalia mantaly gum for their sustained-release and bioadhesive properties. The native gum (NTM) was modified by microwave irradiation for 20 seconds (MTM20) and 60 seconds (MTM60) and characterized using microscopy, Fourier transform infrared spectroscopy (FTIR) and packing properties. The effects of the thermally induced molecular reorientation were determined. Tablet formulations of naproxen were produced by direct compression. The mechanical, bioadhesive and release properties of the formulations were determined. Irradiation of NTM improved the gum's flow properties, resulting in Carr's Index and Hausner's ratios lower than 16% and 1.25, respectively. Swelling studies showed that MTM20 and MTM60 had lower water absorption capacity and swelling index values, while packing properties improved upon irradiation, as depicted by lower tapped density values. FTIR spectra of samples showed that the irradiated gums were distinct from the native gums and did not interact with naproxen sodium. The gum's mechanical properties improved with MTM20 and MTM60 and sustained-release action of up 12 h was obtained. Inclusion of hydroxypropyl methylcellulose (HPMC) in the tablet formulations proved critical for bioadhesion. Microwave irradiation of native Terminalia mantaly gum improved the flow, mechanical and sustained-release properties of Naproxen tablets, and the addition of HPMC increased bioadhesion properties. The tablet properties of the native gum were significantly improved after 20 s of microwave irradiation.

Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability.

PubMed

Nakata, Ryo; Osumi, Yu; Miyagawa, Shoko; Tachibana, Akira; Tanabe, Toshizumi

2015-07-01

Keratin was extracted as a reduced form from wool, which was then subjected to acetamidation, carboxymethylation or aminoethylation at abundant free cysteine residues to give acetamidated keratin (AAK), carboxymethylated keratin (CMK) and aminoethylated keratin (AEK). Hydrogels were prepared from intact and three chemically modified keratins simply by concentrating their aqueous solution and subsequent cooling. The lowest concentration to form a hydrogel without fluidity was 110 mg/ml for AAK, 120 mg/ml for AEK, 130 mg/ml for keratin and 180 mg/ml for CMK. Comparing with a hydrogel just prepared (swelling ratio: 600-700), each hydrogel slightly shrank in an acidic solution. While AAK hydrogel little swelled in neutral and basic solutions, other hydrogels became swollen and CMK hydrogel reached to dissolution. Hydrogels of keratin, AAK and AEK were found to support cell proliferation, although cell elongation on AAK and AEK hydrogel was a little suppressed. On the other hand, CMK hydrogel did not seem to be suitable for a cell substrate because of its high swelling in culture medium. Evaluation of the hydrogels as a drug carrier showed that keratin and AAK hydrogels were good sustained drug release carriers, which showed the drug release for more than three days, while the release from AEK and CMK hydrogels completed within one day. Thus, keratin and chemically modified keratin hydrogels, especially keratin and AAK hydrogels, were promising biomaterials as a cell substrate and a sustained drug release carrier. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Cu2+, Co2+ and Cr3+ doping of a calcium phosphate cement influences materials properties and response of human mesenchymal stromal cells.

PubMed

Schamel, Martha; Bernhardt, Anne; Quade, Mandy; Würkner, Claudia; Gbureck, Uwe; Moseke, Claus; Gelinsky, Michael; Lode, Anja

2017-04-01

The application of biologically active metal ions to stimulate cellular reactions is a promising strategy to accelerate bone defect healing. Brushite-forming calcium phosphate cements were modified with low doses of Cu 2+ , Co 2+ and Cr 3+ . The modified cements released the metal ions in vitro in concentrations which were shown to be non-toxic for cells. The release kinetics correlated with the solubility of the respective metal phosphates: 17-45 wt.-% of Co 2+ and Cu 2+ , but <1 wt.-% of Cr 3+ were released within 28days. Moreover, metal ion doping led to alterations in the exchange of calcium and phosphate ions with cell culture medium. In case of cements modified with 50mmol Cr 3+ /mol β-tricalcium phosphate (β-TCP), XRD and SEM analyses revealed a significant amount of monetite and a changed morphology of the cement matrix. Cell culture experiments with human mesenchymal stromal cells indicated that the observed cell response is not only influenced by the released metal ions but also by changed cement properties. A positive effect of modifications with 50mmol Cr 3+ or 10mmol Cu 2+ per mol β-TCP on cell behaviour was observed in indirect and direct culture. Modification with Co 2+ resulted in a clear suppression of cell proliferation and osteogenic differentiation. In conclusion, metal ion doping of the cement influences cellular activities in addition to the effect of released metal ions by changing properties of the ceramic matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

Orthodontic cement with protein-repellent and antibacterial properties and the release of calcium and phosphate ions.

PubMed

Zhang, Ning; Weir, Michael D; Chen, Chen; Melo, Mary A S; Bai, Yuxing; Xu, Hockin H K

2016-07-01

White spot lesions often occur in orthodontic treatments. The objective of this study was to develop a novel resin-modified glass ionomer cement (RMGI) as an orthodontic cement with protein-repellent, antibacterial and remineralization capabilities. Protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC), antibacterial dimethylaminohexadecyl methacrylate (DMAHDM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP) were incorporated into a RMGI. Enamel shear bond strength (SBS) was determined. Calcium (Ca) and phosphate (P) ion releases were measured. Protein adsorption onto specimens was determined by a micro bicinchoninic acid method. A dental plaque microcosm biofilm model was tested. Increasing the NACP filler level increased the Ca and P ion release. Decreasing the solution pH increased the ion release. Incorporating MPC into RMGI reduced protein adsorption, which was an order of magnitude less than that of commercial controls. Adding DMAHDM and NAg into RMGI yielded a strong antibacterial function, greatly reducing biofilm viability and acid production. Biofilm CFU counts on the multifunctional orthodontic cement were 3 orders of magnitude less than that of commercial control (p<0.05). These benefits were achieved without compromising the enamel shear bond strength (p>0.1). A novel multifunctional orthodontic cement was developed with strong antibacterial and protein-repellent capabilities for preventing enamel demineralization. The new cement is promising to prevent white spot lesions in orthodontic treatments. The method of incorporating four bioactive agents may have wide applicability to the development of other bioactive dental materials to inhibit caries. Copyright © 2016 Elsevier Ltd. All rights reserved.

A short term quality control tool for biodegradable microspheres.

PubMed

D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

2014-06-01

Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.

Preparation and evaluation of injectable Rasagiline mesylate dual-controlled drug delivery system for the treatment of Parkinson's disease.

PubMed

Jiang, Ying; Zhang, Xuemei; Mu, Hongjie; Hua, Hongchen; Duan, Dongyu; Yan, Xiuju; Wang, Yiyun; Meng, Qingqing; Lu, Xiaoyan; Wang, Aiping; Liu, Wanhui; Li, Youxin; Sun, Kaoxiang

2018-11-01

A microsphere-gel in situ forming implant (MS-Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson's disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM-MS prepared by a modified emulsion-phase separation method and optimized by Box-Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p < .01) in the initial high plasma drug concentration of the RM-MS-Gel ISFI system compared to that of the single RM-MS and RM-in situ gel systems after intramuscular injection to rats. A pharmacodynamic study demonstrated a significant reduction (p < .05) in 6-hydroxydopamine-induced contralateral rotation behavior and an effective improvement (p < .05) in dopamine levels in the striatum of the lesioned side after 28 days in animals treated with the RM-MS-Gel ISFI compared with that of animals treated with saline. MS-embedded in situ phase transition gel is superior for use as a biodegradable and injectable sustained drug delivery system with a low initial burst and long period of drug release for highly hydrophilic small molecule drugs.

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

PubMed Central

Geer, David J.; Swartz, Daniel D.; Andreadis, Stelios T.

2005-01-01

Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal. PMID:16314471

Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery.

PubMed

Villanova, J C O; Ayres, E; Carvalho, S M; Patrício, P S; Pereira, F V; Oréfice, R L

2011-03-18

Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release. Copyright © 2011 Elsevier B.V. All rights reserved.

Organic-inorganic hybrid nanoparticles controlled delivery system for anticancer drugs.

PubMed

Di Martino, Antonio; Guselnikova, Olga A; Trusova, Marina E; Postnikov, Pavel S; Sedlarik, Vladimir

2017-06-30

The use of organic-inorganic hybrid nanocarriers for controlled release of anticancer drugs has been gained a great interest, in particular, to improve the selectivity and efficacy of the drugs. In this study, iron oxide nanoparticles were prepared then surface modified via diazonium chemistry and coated with chitosan, and its derivative chitosan-grafted polylactic acid. The purpose was to increase the stability of the nanoparticles in physiological solution, heighten drug-loading capacity, prolong the release, reduce the initial burst effect and improve in vitro cytotoxicity of the model drug doxorubicin. The materials were characterized by DLS, ζ-potential, SEM, TGA, magnetization curves and release kinetics studies. Results confirmed the spherical shape, the presence of the coat and the advantages of using chitosan, particularly its amphiphilic derivative, as a coating agent, thereby surpassing the qualities of simple iron oxide nanoparticles. The coated nanoparticles exhibited great stability and high encapsulation efficiency for doxorubicin, at over 500μg per mg of carrier. Moreover, the intensity of the initial burst was clearly diminished after coating, hence represents an advantage of using the hybrid system over simple iron oxide nanoparticles. Cytotoxicity studies demonstrate the increase in cytotoxicity of doxorubicin when loaded in nanoparticles, indirectly proving the role played by the carrier and its surface properties in cell uptake. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization of protein cross-linking in bicomponent electrospun scaffolds for therapeutic use

NASA Astrophysics Data System (ADS)

Papa, Antonio; Guarino, Vincenzo; Cirillo, Valentina; Oliviero, Olimpia; Ambrosio, Luigi

2015-12-01

Bio-instructive electrospun scaffolds based on the combination of synthetic polymers, such as PCL or PLLA, and natural polymers (e.g., collagen) have been extensively investigated as temporary extracellular matrix (ECM) analogues able to support cell proliferation and stem cell differentiation for the regeneration of several tissues. The growing use of natural polymers as carrier of bioactive molecules is introducing new ideas for the design of polymeric drug delivery systems based on electrospun fibers with improved bioavailability, therapeutic efficacy and programmed drug release. In particular, the release mechanism is driven by the use of water soluble proteins (i.e., collagen, gelatin) which fully degrade in in vitro microenvironment, thus delivering the active principles. However, these protein are generally rapidly digested by enzymes (i.e., collagenase) produced by many different cell types, both in vivo and in vitro with significant drawbacks in tissue engineering and controlled drug delivery. Here, we aim at investigating different chemical strategies to improve the in vitro stability and mechanical strength of scaffolds against enzymatic degradation, by modifying the biodegradation rates of proteins embedded in bicomponent fibers. By comparing scaffolds treated by different cross-linking agents (i.e., GC, EDC, BDDGE), we have provided an extensive morphological/chemical/physical characterization via SEM and TGA to identify the best conditions to control drug release via protein degradation from bicomponent fibers without compromising in vitro cell response.

Optimization of protein cross-linking in bicomponent electrospun scaffolds for therapeutic use

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

Papa, Antonio; IMAST SCaRL, Piazza Bovio 22, 80133 Naples; Guarino, Vincenzo, E-mail: vincenzo.guarino@cnr.it

Bio-instructive electrospun scaffolds based on the combination of synthetic polymers, such as PCL or PLLA, and natural polymers (e.g., collagen) have been extensively investigated as temporary extracellular matrix (ECM) analogues able to support cell proliferation and stem cell differentiation for the regeneration of several tissues. The growing use of natural polymers as carrier of bioactive molecules is introducing new ideas for the design of polymeric drug delivery systems based on electrospun fibers with improved bioavailability, therapeutic efficacy and programmed drug release. In particular, the release mechanism is driven by the use of water soluble proteins (i.e., collagen, gelatin) which fullymore » degrade in in vitro microenvironment, thus delivering the active principles. However, these protein are generally rapidly digested by enzymes (i.e., collagenase) produced by many different cell types, both in vivo and in vitro with significant drawbacks in tissue engineering and controlled drug delivery. Here, we aim at investigating different chemical strategies to improve the in vitro stability and mechanical strength of scaffolds against enzymatic degradation, by modifying the biodegradation rates of proteins embedded in bicomponent fibers. By comparing scaffolds treated by different cross-linking agents (i.e., GC, EDC, BDDGE), we have provided an extensive morphological/chemical/physical characterization via SEM and TGA to identify the best conditions to control drug release via protein degradation from bicomponent fibers without compromising in vitro cell response.« less

Preparation of hollow magnetite microspheres and their applications as drugs carriers

PubMed Central

2012-01-01

Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. Graphical abstract Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications. PMID:22490731

Comprehensive Isotopic and Elemental Analysis of a Multi-Oxide Glass By Multicollector ICP-MS in Isotope Substitution Studies

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

v, Mitroshkov; JV, Ryan

2016-04-07

Multicollector ICP-MS was used to comprehensively analyze different types of isotopically-modified glass created in order to investigate the processes of glass corrosion in the water. The analytical methods were developed for the analyses of synthesized, isotopically-modified solid glass and the release of glass constituents upon contact with deionized water. To validate the methods, results from an acid digestion sample of the Analytical Reference Glass (ARG) showed good agreement when compared to data from multiple prior analyses on the same glass [Smith-1]. In this paper, we present the results of this comprehensive analysis from the acid digestion of six types ofmore » isotopically-modified glass and the release of glass constituents into water corrosion after one year of aqueous corrosion.« less

PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release.

PubMed

Scheeren, Laís E; Nogueira, Daniele R; Macedo, Letícia B; Vinardell, M Pilar; Mitjans, Montserrat; Infante, M Rosa; Rolim, Clarice M B

2016-02-01

The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis of silver-containing calcium aluminate particles and their effects on a MTA-based endodontic sealer.

PubMed

Almeida, Luiza Helena S; Moraes, Rafael R; Morgental, Renata D; Cava, Sérgio S; Rosa, Wellington Luiz O; Rodrigues, Patrícia; Ribeiro, Anderson S; Só, Marcus; Pappen, Fernanda G

2018-05-19

To synthetize calcium aluminate (C3A) and silver-containing C3A particles (C3A+Ag) testing their effects on the properties of a MTA-based endodontic sealer in comparison to an epoxy resin- and a calcium silicate-based sealer. Pure C3A and C3A+Ag particles were synthesized by a chemical method and characterized using XRD to identify crystalline phases. SEM/EDS analysis investigated morphology, particle size, and elemental composition of particles. Setting time, flow, radiopacity, water sorption and solubility of commercial and modified sealers were evaluated according to ISO 6876/2012. The pH and ions release were measured using a pHmeter and a microwave induced plasma optical emission spectrometer. The inhibition of biofilm growth was evaluated by confocal laser scanning microscopy (CLSM). Data were rank transformed and analyzed by ANOVA and Tukey test (P<0.05). The C3A particles showed an irregular grain agglomerated structure with voids and pores. In C3A+Ag particles, Ag modified the material morphology, confirming the deposition of Ag. The physicochemical properties of the modified MTA-based sealer were similar to the commercial material, except for the significant increase in Ca +2 release. However, there was no Ag release. Setting time, flow, radiopacity, water sorption and solubility were adequate for all materials. All the materials showed alkaline pH. Antibiofilm effect was improved in the presence of C3A particles, while the biofilm inhibition was lower in the presence of Ag. The modified sealer presented improved antibiofilm properties and calcium release, without dramatic effects on the other characteristics. It is expected a positive effect in its antimicrobial behavior. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

NASA Astrophysics Data System (ADS)

Ranjan, Amalendu P.; Zeglam, Karim; Mukerjee, Anindita; Thamake, Sanjay; Vishwanatha, Jamboor K.

2011-07-01

The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 ± 3.7 to 260 ± 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.

TSCA Experimental Release Application (TERA) for modified Gordonia terrae, R-13-0001 and modified Rhodococcus jostii, R-13-0002

EPA Pesticide Factsheets

TERAs submitted by the US Army Engineer Research and Development Center, Vicksburg, MS and US Army Corps of Engineers, Seattle, WA. These microorganisms will be used in a field demonstration of bioaugmentation to enhance RDX degradation.

TRACKING GENE FLOW FROM A GENETICALLY MODIFIED CREEPING BENTGRASS -- METHODS, MEASURES AND LESSONS LEARNED

EPA Science Inventory

Creeping bentgrass (CBG) expressing an engineered gene for resistance to glyphosate herbicide is one of the first genetically modified (GM) perennial crops to undergo regulatory review for commercial release by the US Department of Agriculture Animal Plant Health and Inspection S...

Stimulatory effect of exogenous diadenosine tetraphosphate on insulin and glucagon secretion in the perfused rat pancreas

PubMed Central

Silvestre, Ramona A; Rodríguez-Gallardo, Jovita; Egido, Eva M; Marco, José

1999-01-01

Diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released by various cells (e.g. platelets and chromaffin cells), and may act as extracellular messengers. In pancreatic B-cells, AP3A and AP4A are inhibitors of the ATP-regulated K+ channels, and glucose increases intracellular levels of both substances.We have studied the effect of exogenous AP3A and AP4A on insulin and glucagon secretion by the perfused rat pancreas.AP3A did not significantly modify insulin or glucagon release, whereas AP4A induced a prompt, short-lived insulin response (≈4 fold higher than basal value; P<0.05) in pancreases perfused at different glucose concentrations (3.2, 5.5 or 9 mM). AP4A-induced insulin release was abolished by somatostatin and by diazoxide. These two substances share the capacity to activate ATP-dependent K+ channels, suggesting that these channels are a potential target for AP4A in the B-cell.AP4A stimulated glucagon release at both 3.2 and 5.5 mM glucose. This effect was abolished by somatostatin.The results suggest that extracellular AP4A may play a physiological role in the control of insulin and glucagon secretion. PMID:10516664

Stimulatory effect of exogenous diadenosine tetraphosphate on insulin and glucagon secretion in the perfused rat pancreas.

PubMed

Silvestre, R A; Rodríguez-Gallardo, J; Egido, E M; Marco, J

1999-10-01

1. Diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released by various cells (e.g. platelets and chromaffin cells), and may act as extracellular messengers. In pancreatic B-cells, AP3A and AP4A are inhibitors of the ATP-regulated K+ channels, and glucose increases intracellular levels of both substances. 2. We have studied the effect of exogenous AP3A and AP4A on insulin and glucagon secretion by the perfused rat pancreas. 3. AP3A did not significantly modify insulin or glucagon release, whereas AP4A induced a prompt, short-lived insulin response ( approximately 4 fold higher than basal value; P<0.05) in pancreases perfused at different glucose concentrations (3.2, 5.5 or 9 mM). AP4A-induced insulin release was abolished by somatostatin and by diazoxide. These two substances share the capacity to activate ATP-dependent K+ channels, suggesting that these channels are a potential target for AP4A in the B-cell. 4. AP4A stimulated glucagon release at both 3.2 and 5.5 mM glucose. This effect was abolished by somatostatin. 5. The results suggest that extracellular AP4A may play a physiological role in the control of insulin and glucagon secretion.

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

PubMed

Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery system for vaginal administration of protein therapeutics.