Reduction In Release Rate Research Articles

Strong and conductive chitosan-reduced graphene oxide nanocomposites for transdermal drug delivery.

Chitosan-reduced graphene oxide (rGO) nanocomposites were synthesized through a biocompatible reduction process and were first reported for applications in transdermal drug delivery devices, such as microneedle arrays. Introducing rGO improved the mechanical properties of chitosan, with the strongest nanocomposites containing 1 wt% and 2 wt% rGO chosen to undergo drug delivery testing. The addition of rGO increased the electrical conductivity of chitosan, allowing the nanocomposites to be used for electroporation or iontophoresis drug delivery applications. The rGO content was proven to be an important factor for drug delivery due to the bonding of drug onto rGO. Increasing the rGO content allowed for a quicker and more substantial drug release, allowing for a controlled drug release rate. The nanocomposites also exhibited pH dependent release behaviour, with a reduced release rate in the presence of an acidic medium. The biodegradation rate of chitosan decreased when rGO was added but the biodegradation rates of the nanocomposites are not dependent on the rGO concentration, with nanocomposites of 1 wt% and 2 wt% rGO possessing a similar biodegradation path. The use of the nanocomposite in a microneedle array was shown through compression testing and drug release testing in a pseudo-in vivo environment.

Further studies on polystyrene/cerium (IV) oxide system: melt blending and interaction with montmorillonite

In order to clarify questions raised from a recent study on the polymer/cerium (IV) oxide (CeO2) system, polystyrene/CeO2 was prepared by melt blending, which produces only microscale dispersed CeO2. The incorporation of CeO2 moderately enhances the thermal stability of the composites. Because of the limited surface area of microscale CeO2 particles compared with nanoscale particles, the microscale dispersed CeO2 induces negligible peak heat release rate reduction in cone calorimetry. Combination of CeO2 with organoclay does not show any advantages with either microdispersion of nanodispersion of CeO2 in polystyrene and polymethylmethacrylate matrices. In summary, the nanodispersion (i.e. surface area) of CeO2 particles is a critical factor in fire retardancy of the composites. Copyright © 2013 John Wiley & Sons, Ltd.

Studies on the stability and kinetics of drug release of dexamethasone phosphate intercalated layered double hydroxides nanohybrids

We report the intercalation of dexamethasone sodium phosphate drug in Mg/Al layered double hydroxides (LDHs) through co-precipitation technique. The as-synthesized nanohybrid was characterized by XRD, FTIR and thermal analysis techniques, which reveal that the dexamethasone phosphate anions are accommodated within the brucite layers. The shifting in the stretching frequency of phosphate anion of the drug provides strong evidence that the drugs are bonded to LDHs through electrostatic force. The surface charge analysis suggested the possibility of charge manipulation in LDHs system by varying intercalated anions. In-vitro release study of as-synthesized nanohybrid particles suggests a significant reduction in release rate of dexamethasone phosphate anions from Mg/Al–Dexa LDHs and is due to confinement of drugs in the interlayer. The mechanism of drugs diffusion in nanohybrid is studied by using dissolution–diffusion kinetic model, which reveals that it is probably due to dissolution and intra-particle diffusion of anions in the physiological medium.

Fire retardancy of polyurea and silylated α-zirconium phosphate composites with ammonium polyphosphate

The thermal stability and fire performance of polyurea with silylated α-zirconium phosphate and ammonium polyphosphate are studied. The addition of ammonium polyphosphate reduces the thermal stability of the composites with and without silylated α-zirconium phosphate. The peak heat release rate reduction is lower in microscale combustion calorimetry than in cone calorimetry, which suggests that some physical process, like the formation of a barrier, is the process by which fire retardancy is obtained. Based on cone calorimetry, the peak heat release rate reduction does not depend on the loading of the silylated zirconium phosphate, and the combination with ammonium polyphosphate is less effective than ammonium polyphosphate alone.

Disulfide Cross-Linked Phosphorylcholine Micelles for Triggered Release of Camptothecin

A series of block copolymers based on 2-methacryloyloxyethyl phosphorylcholine (MPC) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Incorporation of dihydrolipoic acid (DHLA) into the hydrophobic block led to formation of block copolymer micelles in water. The micelles were between 15 and 30 nm in diameter, as characterized by dynamic light scattering (DLS), with some size control achieved by adjusting the hydrophobic/hydrophilic balance. Cross-linked micelles were prepared by disulfide formation, and observed to be stable in solution for weeks. The micelles proved amenable to disassembly when treated with a reducing agent, such as dithiothreitol (DTT), and represent a potential delivery platform for chemotherapeutic agents. As a proof-of-concept, camptothecin (CPT) was conjugated to the polymer scaffold through a disulfide linkage, and release of the drug from the micelle was monitored by fluorescence spectroscopy. These CPT-loaded prodrug micelles showed a reduction in release rate compared to physically encapsulated CPT. The use of disulfide conjugation facilitated drug release under reducing conditions, with a half-life (t1/2) of 5.5 h in the presence of 3 mM DTT, compared to 28 h in PBS. The toxicity of the micellar prodrugs was evaluated in cell culture against human breast (MCF7) and colorectal (COLO205) cancer cell lines.

The role of dispersion of LDH in fire retardancy: The effect of different divalent metals in benzoic acid modified LDH on dispersion and fire retardant properties of polystyrene– and poly(methyl-methacrylate)–LDH–B nanocomposites

The influence of three different divalent metals, calcium, magnesium and zinc, using benzoate-modified layered double hydroxides (LDHs), on the dispersion and fire properties of polystyrene (PS) and poly(methyl-methacrylate) (PMMA) is investigated. PS- and PMMA-layered double hydroxide (PS/LDHs PMMA/LDHs) nanocomposites are prepared by in situ bulk polymerization in the presence of the benzoate-modified LDHs. The morphology of the nanocomposites is characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). XRD results indicate that the characteristic layered structure of Ca–Al–LDH–B completely disappear in both polymers, whereas for Zn–Al–LDH–B and Mg–Al–LDH–B that is not the case. TEM confirms excellent dispersion and exceptional distribution of exfoliated Ca–Al–LDH–B within both polymer matrices, while for Zn–Al–LDH–B and Mg–Al–LDH–B dispersion is poorer with more tactoids present. Thermal stability and fire properties are investigated by thermogravimetric analysis (TGA) and cone calorimetry (CC). All PMMA nanocomposites show enhanced thermal stability compared to neat PMMA, while thermal stability of PS is enhanced only by the addition of Ca–Al–LDH–B. PS/Ca–Al–LDH–B and PS/Zn–Al–LDH–B systems show better fire properties compared to the PS/Mg–Al–LDH–B; peak heat release rate reduction is 42 and 41%, respectively, vs. only 15% for the PS/Mg–Al–LDH–B at 10% LDH loading. The largest peak heat release rate reduction (PHRR), 52%, is measured for the PMMA/Mg–Al–LDH–B nanocomposites at 10% LDH loading, although dispersion is very poor. PHRR reduction of the PMMA/Ca–Al–LDH–B nanocomposites at 10% LDH loading is 45%, while 30% reduction of the PHRR is measured for nanocomposites containing 10% Zn–Al–LDH–B.

Encapsulation and Controlled Release of Recombinant Human Erythropoietin from Chitosan-Carrageenan Nanoparticles

Novel chitosan-carrageenan nanoparticles were produced through the process of ionotropic gelation for the encapsulation and controlled release of recombinant human erythropoietin (rHu-EPO). The effects of chitosan concentration, chitosan to carrageenan mass ratio and solution pH on the nanoparticle diameter, polydispersity and surface charge were explored through both screening and response surface modeling (RSM) methods. The chitosan-carrageenan nanoparticles created had particle diameters between 200 and 1000 nm, surfaces charges between 40 and 55 mV, and polydispersity between 0.2 and 0.35. RSM optimized chitosan-carrageenan nanoparticles demonstrated an increased rHu-EPO encapsulation efficiency of 47.97 ± 4.10% and a more sustained in vitro release of ~50% over a 2 week period when compared to previous nano/microparticle delivery systems. Studies on the effect of surface charge and chitosan molecular weight on the encapsulation and controlled release of rHu-EPO revealed that increasing either led to improved encapsulation efficiency and reduced release rate.

How many Orius laevigatus are needed for effective western flower thrips, Frankliniella occidentalis, management in sweet pepper?

Frankliniella occidentalis (Pergande) is a primary pest of greenhouse crops worldwide, in organic and integrated pest management control practices, Orius spp. are frequently released for thrips control. However, Orius spp. are relatively expensive to produce. More cost-efficient rearing systems and reduced release rate might reduce the expense. In these trials, we released Orius laevigatus (Fieber) at different rates with or without simultaneous release the predatory mite Amblyseius swirskii Athias-Henriot, another known thrips predator, which is less expensive to rear. There was no significant difference in the number of O. laevigatus recovered in which either 2 or 6 individuals were released per square meter, and there was no difference in thrips control among any of the release strategies using O. laevigatus, suggesting that a reduced release rate can maintain effective thrips control. There was no significant difference in the quality or quantity of the pepper yield between treatments in which either 2 or 6 Orius/m 2 or Orius plus A. swirskii were released.

Development and in vivo evaluation of novel monolithic controlled release compositions of galantamine hydrobromide as against reservoir technology

The objective of this study is to develop and in vivo evaluation of novel monolithic matrix mini tablets approach to control the release of galantamine hydrobromide (GAH) in comparison with desired release profile to the Innovator formulation Razadyne® ER capsules. The direct compression method was employed for preparation of matrix mini tablets as against reservoir multiparticulate pellets of innovator formulation. The matrix swellings, dissolution similarity, mean dissolution time and dissolution efficiency of formulations were evaluated. It was found that increase in the concentration of high viscosity hydroxypropylcellulose (HPC) results reduction in release rate. The drug release was shown to be pH dependent with faster rate at lower pH. The release of GAH followed first order shifting to dissolution dependent by increase of HPC content. The formulation showed stability of drug release. In vivo prediction was done by Wagner–Nelson method. Prediction errors were estimated for Cmax and area under curve (AUC) and found to be not exceeding 15%. In vivo study in human volunteers confirmed the similarity between test and innovator formulations and pharmacokinetic values were comparable between actual and predicted. These results suggest that novel monolithic matrix approach could be suitable technique to formulate controlled release GAH.

Poly(lactic acid)-coated mesoporous silica nanosphere for controlled release of venlafaxine

Two types of mesoporous silica nanospheres (MSNs) were synthesized for use as controlled-release agents. One was prepared by grafting with 5,6-dihydroxyhexylsilane (DH-MSN) and the other one by further coating with cholic acid-crosslinked poly(lactic acid) (CA-PLA-MSN). We studied the release of the antidepressant venlafaxine from each of the materials in simulated gastric fluid (SGF), in simulated gastric acid solution (SGA), and in simulated intestinal fluid without pancreatin (SIF). The CA-PLA-MSN material was able to significantly delay the release of the drug in intestinal condition compared with gastric acid surrounding due to the fast decomposition rate of PLA in gastric acid. Moreover, it successfully avoided the initial burst to a certain extent in SGF. The enzyme pepsin played a favorable obstruct role in both DH-MSN and CA-PLA-MSN systems to reduce release rate. A model based on Weibull model was built to fit the release results, and based on it, the mechanisms about release processes were brought out tentatively.

Field responses of the Asian larch bark beetle, Ips subelongatus, to potential aggregation pheromone components: disparity between two populations in northeastern China

Abstract Behavioral responses of the Asian larch bark beetle, Ips subelongatus Motsch. to three potential aggregation pheromone components, ipsenol (racemic or [−]-enantiomer), ipsdienol (racemic or [+]-enantiomer) and 3-methyl-3-buten-1-ol, were tested using partial or full factorial experimental designs in two provinces (Inner Mongolia and Jilin) of northeastern China. Our field bioassays in Inner Mongolia (Larix principis-rupprechtii Mayr. plantation) clearly showed that ipsenol, either racemic or 97%-(−)-enantiomer, was the only compound that significantly attracted both sexes of I. subelongatus, while all other compounds (singly or in combinations) were unattractive. There were no two- or three-way synergistic interactions. However, in Jilin Province (L. gmelini[Rupr.] Rupr. Plantation), all the individual compounds tested were inactive, except a very weak activity by 97%-(−)-ipsenol in 2004 when the beetle population was very high. While a combination of ipsenol and ipsdienol (racemates or enantiomerically pure natural enantiomers) showed a significant attraction for both sexes of I. subelongatus, indicating a two-way synergistic interaction between these two major components, addition of 3-methyl-3-buten-1-ol to these active binary blend(s) did not have any effects on trap catches, suggesting that ipsenol and ipsdienol are the synergistic aggregation pheromone components of I. subelongatus in Jilin Province. It seems that 97%-(−)-ipsenol in Inner Mongolia or the binary blend of 97%-(−)-ipsenol and 97%-(+)-ipsdienol in Jilin Province are superior to their corresponding racemates, which might be due either to weak inhibitory effects of the antipode enantiomers or to reduced release rates of the active natural enantiomer(s) in the racemate(s). Our current bioassay results suggest that there is a strong geographical variation in aggregation pheromone response of I. subelongatus in northeastern China. Future research on the pheromone production and response of I. subelongatus from different regions in Northeast Asia will surely improve our understanding of the dynamic aggregation pheromone system of this economically important forest pest insect.

Assemblage of drug release modules: Effect of module shape and position in the assembled systems on floating behavior and release rate

The aim of this work was to study the clindamycin release kinetics from floating delivery systems consisting of two modules assembled in void configuration, according to the modified release technology platform known as Dome Matrix®. Two modules differently shaped, i.e., female and male, formulated as swellable matrices and containing clindamycin, were assembled by friction interlocking. Then, by stacking additional female modules without drug on the assembled two-module floating system, modulation of clindamycin release rate and kinetics was attained. The additional modules stacked on the assembled system acted as a transient barrier to clindamycin release from the void configuration. Inertness, dissolution/erosion or swelling behavior characterized their performance as matrices in simulated gastric fluid. In particular, we found that stacking additional barrier modules on the bases of void configuration, the drug release rate and kinetics of the assembled system were modified in dependence on the composition of module added. In particular, the quickly soluble module exerted an influence on the release rate in the late time of delivery. The swellable module produced a significant reduction in release rate of void assembly, but the release mechanism remained the same. Finally, the inert module led to a substantial linearization of the release profile with a minimal reduction in release rate.

Onset Coding Is Degraded in Auditory Nerve Fibers from Mutant Mice Lacking Synaptic Ribbons

Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system.

A comparison of the fire retardancy of poly(methyl methacrylate) using montmorillonite, layered double hydroxide and kaolinite

Montmorillonite, layered double hydroxide and kaolinite, have been used to make (nano)composites with poly(methyl methacrylate). X-ray diffraction and transmission electron microscopy were used to characterize the morphology and the thermal stability and fire properties have been studied by thermogravimetric analysis and cone calorimetry. The results show that LDH and MMT are better dispersed in PMMA than is kaolinite; the MMT layers have a higher aspect ratio than does the LDH. PMMA + MMT and PMMA + LDH composites have higher thermal stability than PMMA + kaolinite composite. The peak of heat release rate reduction is 55% for the PMMA + MMT composite at 10%, 45% for PMMA + LDH and 23% for PMMA-kaolinite.

Synergistic effect of carbon nanotubes and decabromodiphenyl oxide/Sb 2O 3 in improving the flame retardancy of polystyrene

Brominated flame retardant polystyrene composites were prepared by melt blending polystyrene, decabromodiphenyl oxide, antimony oxide, multi-wall carbon nanotubes and montmorillonite clay. Synergy between carbon nanotubes and clay and the brominated fire retardant was studied by thermogravimetric analysis, microscale combustion calorimetry and cone calorimetry. Nanotubes are more efficient than clay in improving the flame retardancy of the materials and promoting carbonization in the polystyrene matrix. Comparison of the results from the microscale combustion calorimeter and the cone calorimeter indicate that the rate of change of the peak heat release rate reduction in the microscale combustion calorimeter was slower than that in the cone. Both heat release capacity and reduction in the peak heat release rate in the microscale combustion calorimeter are important for screening the flame retardant materials; they show good correlations with the cone parameters, peak heat release rate and total heat released.

In-Vitro Release Kinetics and Stability of Anticardiovascular Drugs-Intercalated Layered Double Hydroxide Nanohybrids

We report the intercalation and characterization of pravastatin and fluvastatin drugs in Mg(II)/Al(III) layered double hydroxides (LDHs) to form novel nanohybrid hydroxides through the coprecipitation technique. powder X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis techniques reveal that the drugs are accommodated within the brucite layers. Structural characterization, computed results, and atomic force microscopy image analysis demonstrate that the fluvastatin anions are attached with the brucite as a monolayer, whereas the pravastatin anions form a multilayer. The shift in the stretching frequency of carboxylate anion of statin drugs provides evidence that the drugs are electrostatically bonded to LDHs. X-ray diffraction and thermal analysis studies performed after keeping the nanohybrid particles at 75 +/- 10% relative humidity atmosphere, indicate their physical stability due to proper confinement of drugs within the layers. In-vitro release study of developed nanohybrid particles suggests that the significant reduction in release rate of fluvastatin anions from fluvastatin intercalated LDHs is due to its hydrophobic nature and it can be further controlled by varying the concentration in physiological medium. After release, the data were fitted to the dissolution-diffusion kinetic model. The mechanism of drugs diffusion in hydrophobic nanohybrid is probably due to heterogeneous diffusion via anion exchange, while in a hydrophilic nanohybrid, it is due to intraparticle diffusion via anion exchange with the anions in the physiological medium.

Development and <i>in-vitro</i> Evaluation of a Topical Drug Delivery System Containing Betamethazone Loaded Ethyl Cellulose Nanospheres

Purpose: Lipid nanospheres are used for the passive targeting of cosmetic agents to skin, thereby achieving major benefits such as reduction of total dose and avoidance of systemic absorption. The present study was carried out to exploit the feasibility of using polymeric nanospheres as an alternative and cheaper carrier for targeting corticosteroids to the skin. Methods: Nanospheres were prepared from ethyl cellulose by a modified method of desolvation and cross linking. The drug betamethazone was incorporated into nanospheres and the drug: polymer ratio was evaluated to determine the carrier capacity of the polymer. In-vitro release studies of drug-loaded nanospheres were carried out by the centrifugal ultrafiltration method. The kinetics of release was determined and fitted to an empirical equation. The release of drug from drug-loaded nanospheres dispersing in a conventional cream was evaluated. A comparative in-vitro diffusion study was carried out between a commercial brand of cream and the cream incorporating nanospheres. Results: Formulation of nanospheres of betamethazone by a modified method produced discrete particles. Studies on drug:polymer ratio showed a linear relationship between drug concentration and percentage of loading. The in-vitro release of drug-loaded nanospheres was found to be first order. The comparative in-vitro diffusion study between the commercial cream and the formulated cream showed a marked reduction in release rate from nanospheres-bound cream. Conclusion: Formulated topical cream containing nanospheres of betamethazone was found to be a potential dermal delivery system for sustaining the release of the drug. Keywords: Nanospheres, desolvation and cross-linking method, ethyl cellulose, betamethazone, in-vitro diffusion studies.> Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 495-500

Impact of Temperature on Plum Curculio (Coleoptera: Curculionidae) Responses to Odor-Baited Traps

In 2005, captures of overwintered adult plum curculios, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), in standard black masonite pyramid traps deployed in apple (Malus spp.) orchards from half-inch green until fruit reached 7 mm and baited with known attractants did not result in significant captures compared with unbaited traps as they had in 2003 and 2004. These baits included the synthetic aggregation pheromone, grandisoic acid (GA) alone, a six-component synthetic host plant volatile combination (6-Tree) identified from foliar and woody tissues of a Stanley plum tree in combination with GA (6-Tree+GA), and the synthetic fruit volatile benzaldehyde (BEN) in combination with GA (BEN+GA). In 2005, the average daily temperature was below 13 degrees C, much cooler than in 2003 and 2004. We hypothesized that plum curculio could not discriminate between baited and unbaited traps because of reduced release rates of odor-bait stimuli due to their temperature-driven release system. From data collected from 2003 to 2005, we found that plum curculio captures in traps baited with GA alone, 6-Tree+GA, and BEN+GA were significantly related to temperature. We created a predictive model to determine the level of activity, i.e., trap captures in baited traps compared with unbaited traps, we would expect to observe at a particular temperature for these same odor stimuli. Our models predicts that at temperatures between approximately 11 to 13 degrees C we would expect to see no difference between captures in baited and unbaited traps. For captures in odor-baited traps to reach twice those in unbaited traps, our model predicts that temperatures must reach 19.2 degrees C for GA alone, 18.5 degrees C for 6-Tree+GA, and 15.8 degrees C for BEN+GA.

Impact of Temperature on Plum Curculio (Coleoptera: Curculionidae) Responses to Odor-Baited Traps

In 2005, captures of overwintered adult plum curculios, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), in standard black masonite pyramid traps deployed in apple (Malus spp.) orchards from half-inch green until fruit reached 7 mm and baited with known attractants did not result in significant captures compared with unbaited traps as they had in 2003 and 2004. These baits included the synthetic aggregation pheromone, grandisoic acid (GA) alone, a six-component synthetic host plant volatile combination (6-Tree) identified from foliar and woody tissues of a Stanley plum tree in combination with GA (6-Tree+GA), and the synthetic fruit volatile benzaldehyde (BEN) in combination with GA (BEN+GA). In 2005, the average daily temperature was below 13°C, much cooler than in 2003 and 2004. We hypothesized that plum curculio could not discriminate between baited and unbaited traps because of reduced release rates of odor-bait stimuli due to their temperature-driven release system. From data collected from 2003 to 2005, we found that plum curculio captures in traps baited with GA alone, 6-Tree+GA, and BEN+GA were significantly related to temperature. We created a predictive model to determine the level of activity, i.e., trap captures in baited traps compared with unbaited traps, we would expect to observe at a particular temperature for these same odor stimuli. Our models predicts that at temperatures between ≈ 11 to 13°C we would expect to see no difference between captures in baited and unbaited traps. For captures in odor-baited traps to reach twice those in unbaited traps, our model predicts that temperatures must reach 19.2°C for GA alone, 18.5°C for 6-Tree+GA, and 15.8°C for BEN+GA.

Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers

The present study was aimed at developing and exploring the use of mannosylated dendritic architecture for the selective delivery of an anti-tuberculosis drug, rifampicin (RIF) to alveolar macrophages (AM). The mannosylated dendritic architecture was synthesized and characterized by using IR and NMR spectroscopy. RIF was efficiently loaded into mannosylated dendrimer using dissolution method. Various physicochemical and physiological parameters such as UV, SEM, DSC, drug loading, solubilization, pH dependent in-vitro release, hemolytic toxicity, phagocytic AM uptake and cytotoxicity concerning the mannosylated dendrimer were evaluated. RIF loaded mannosylated dendrimer reduced release rate of drug in pH 7.4, hemolytic toxicity and cytotoxicity; whereas enhanced drug release in pH 5.0 and AM uptake was observed. The present novel dendritic system displayed suitability in terms of biocompatibility and site-specific delivery of antitubercular drug RIF.