Greater Release Rate Research Articles

Synthesis and Characterization of Temperature‐/pH‐Responsive Hydrogels for Drug Delivery

AbstractA temperature‐/pH‐responsive hydrogel was successfully prepared by in situ free radical polymerization of N‐isopropyl acrylamide (NIPAm), itaconic acid (IA), and poly (ethylene glycol) methyl ether acrylate (OEGA). The pore size, mechanical strength, and swelling ratio of the P(NIPAm‐IA‐OEGA) were strongly affected by the contents of IA. 5‐Fluorouracil (5‐Fu) was chosen as a model drug, and the maximum drug loading was 68 mg/g. P(NIPAm‐IA‐OEGA) had a much greater release rate in a simulated intestinal fluid environment (47.73 %, 16 h) than in gastric juice (33.11 %, 16 h). The hemolysis test and cytotoxicity test proved that prepared hydrogel had good biocompatibility. In summary, P(NIPAm‐IA‐OEGA) can be used for oral drug delivery systems in cancer therapy.

Transport and retention of phosphorus in soil with addition of Mg-Al layered double hydroxides: Effects of material dosage, flow velocity and pH

Mg-Al layered double hydroxides (LDHs) were applied to soils to control phosphorus (P) loss. Column experiments were conducted with soil and LDHs under saturated conditions to investigate the retention and release of P with various LDHs dosages, flow velocity, and pH. The P retention and retardation of P breakthrough in soil with LDHs were enhanced with increasing LDHs dosages and pH as well as with decreasing flow velocity. The retention of P was successfully analyzed using a two kinetic sites model that accounted for irreversible and reversible retentions. Increasing LDHs dosages, decreasing flow velocity, and increasing pH bring greater maximum retained concentration on the solid phases (Smax1, i.e. irreversible retention) for P in LDHs-soil system. For reversible retention, the greater release rate from site 2 (k2d) than first-order retention rate coefficient on site 2 (k2) for most experiments reflects a rapid release process and near equilibrium transport behavior of P in LDHs-soil system. It is worth noting that the change of soil pH (8–5) and Darcy velocity (0.17–0.65 cm min−1) has little influence on the release of P from soil mixing with LDHs. The stability of LDHs in soil increases with greater LDHs dosages, higher pH, and lower velocity.

Flavour retention in sodium caseinate – Carboxymethylcellulose complex coavervates as a function of storage conditions

Flavour retention in freeze-dried complex coacervates prepared with sodium caseinate and carboxymethylcellulose was followed over storage for 20 days at two relative humidities (0 and 54%) and temperatures (25 and 45 °C). Beta-pinene was used as a model volatile compound. Avrami’s equation mathematical model was equipped to describe the correlation between release rate and storage time. In general, volatile’s retention in the dried powder was considerably affected by the storage conditions along with the wall material characteristics (e.g. protein/polysaccharide ratio, presence of reticulating agents, i.e. glycerol and tannic acid) as a greater rate of release was observed at high relative humidity (RH) and temperature values and low biopolymer addition levels. Moreover, the Arrhenius activation energy Ea was reduced by increasing RH from 0 to 54% while it got either positive or negative values indicating that the release of β-pinene was either related or not to temperature. Rehydration of dried powders in high humidity air conditions and the induced reduction of their effective surface area may account for the decrease of β-pinene retention. Glycerol addition resulted in higher retention of the volatile compound in the powder stored at low RH and temperature (0% RH, 25 °C) as compared to other storage conditions, which was further confirmed by the remarkable increase of half-life release t1/2 from 29 to 9303 days, as this was calculated from the Avrami’s equation mathematical model.

Skin Tissue Engineering for the Infected Wound Site: Biodegradable PLA Nanofibers and a Novel Approach for Silver Ion Release Evaluated in a 3D Coculture System of Keratinocytes and Staphylococcus aureus

Wound infection presents a challenging and growing problem. With the increased prevalence and growth of multidrug-resistant bacteria, there is a mounting need to reduce and eliminate wound infections using methodologies that limit the ability of bacteria to evolve into further drug-resistant strains. A well-known strategy for combating bacterial infection and preventing wound sepsis is through the delivery of silver ions to the wound site. High surface area silver nanoparticles (AgNPs) allowing extensive silver ion release have therefore been explored in different wound dressings and/or skin substitutes. However, it has been recently shown that AgNPs can penetrate into the stratum corneum of skin or diffuse into the cellular plasma membrane, and may interfere with a variety of cellular mechanisms. The goal of this study was to introduce and evaluate a new type of high surface area metallic silver in the form of highly porous silver microparticles (AgMPs). Polylactic acid (PLA) nanofibers were successfully loaded with either highly porous AgMPs or AgNPs and the antimicrobial efficacy and cytotoxicity of the two silver-based wound dressings were assessed and compared. To better mimic the physiological environment in vivo where both human cells and bacteria are present, a novel coculture system combining human epidermal keratinocytes and Staphylococcus aureus bacteria was designed to simultaneously evaluate human skin cell cytotoxicity with antimicrobial efficacy in a three-dimensional environment. We found that highly porous AgMPs could be successfully incorporated in nanofibrous wound dressings, and exhibited comparable antimicrobial efficacy and cytotoxicity to AgNPs. Further, PLA nanofibers containing highly porous AgMPs exhibited steady silver ion release, at a greater rate of release, than nanofibers containing AgNPs. The replacement of AgNPs with the newly introduced AgMPs overcomes concerns regarding the use of nanoparticles and holds great promise as skin substitutes or wound dressings for infected wound sites.

PHOSPHOLIPID ASSEMBLY ON SUPERPARAMAGNETIC NANOPARTICLES FOR THERMORESPONSIVE DRUG DELIVERY APPLICATIONS

Thermoresponsive nanocomposites were prepared by immobilizing a 2–3 nm thick phospholipid layer on the surface of superparamagnetic Fe3O4 nanoparticles via high-affinity avidin/biotin interactions. Morphological and physicochemical surface properties were assessed using transmission electron microscopy, confocal laser scanning microscopy, differential scanning calorimetry, and attenuated total reflectance Fourier transform infrared spectroscopy. The zeta potential of Fe3O4 colloids in phosphate buffered saline (PBS) decreased from -23.6 to -5.0 mV as a consequence of phospholipid immobilization. Nevertheless, heating properties of these superparamagnetic nanoparticles within an alternating magnetic field were not significantly affected. Hyperthermia-relevant temperatures > 40°C were achieved within 10–15 min using a 7-mT magnetic field alternating at a frequency of 1 MHz. Loading of the surface-associated phospholipid layer with the hydrophobic dye dansylcadaverine was accomplished at an efficiency of 479 ng/mg Fe3O4 . Release of this drug surrogate was temperature-dependent, resulting in a 2.5-fold greater release rate when nanoparticles were exposed to a temperature above the experimentally determined melting temperature of 39.7°C. These data underline the feasibility of preparing novel, stimulus-induced drug delivery systems where payload release from a colloid-immobilized phospholipid assembly is triggered by hyperthermia.

Regeneration of Nitrogen Fertility In Disturbed Soils Using Composts

Soil disturbance often results in loss of soil organic matter and nitrogen (N) fertility, making revegetation of barren areas difficult. Yard waste composts are a potential source material to regenerate soil fertility so that revegetation success is improved. The N release behaviors of several compost materials produced within California were evaluated during a long-term, 586-day aerobic incubation. Two general types of compost were tested, including yard waste compost materials (lawn clippings and chipped brush) and cocomposted materials (biosolids bulked and composted with yard waste materials). Nitrogen release from composted material was measured using periodic soil solution extraction and soluble N analysis. Nitrogen release rates varied widely between source materials during the initial portions of the incubation period, with cocomposts having much greater release rates than the yard waste composts. Yard waste composts that were poorly cured or had high woody fiber content showed net immobilization of N during the initial incubation periods, which could potentially lead to N-limitations for plant growth in field conditions. Following additional curing in the soil, however, all yard waste compost materials had positive net N mineralization release rates. Release rates were similar to some of the native soils used as reference materials. The relationship of long-term aerobic N release and several other indicators of mineralizable or “bioavailable” N were evaluated, but the relationship of these other indicators with the aerobic incubation data was low. Because the cumulative N release from yard waste compost materials was a small fraction of the material's total N content, N leaching losses in field conditions are expected to be small and of short duration. Steady, long-term N release patterns were observed from composts throughout the second half of the study and would be expected to continue for an extended period in the field. Composts are shown to provide a suitable replacement source of slowly available N for plant establishment on drastically disturbed, low nutrient soils.

Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method

Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of solid oral dosage forms. The objective of the present study was to investigate the effect of delivery system positioning in accordance with the USP 23-recommended dissolution methods and the proposed modification on drug release from controlled release systems having different operating release mechanisms, namely, swellable floatable, swellable sticking and osmotic pump. The delivery systems were evaluated by placing each dosage form either in the dissolution vessel in accordance with the USP 23 methods or over/below a designed ring/mesh device for achieving full surface exposure to the dissolution medium for sticking or floatable systems respectively. Results indicate that the overall release profiles from the sticking and floatable systems of theophylline are sensitive to their positioning in the dissolution vessel ( P<0.05). Furthermore, release of diltiazem hydrochloride from the sticking system also demonstrated sensitivity ( P<0.05). In contrast, the floatable dosage form of this latter drug with the application of a helical wire sinker, or when it was placed below the ring/mesh assembly, or by allowing the dosage form to float, did not show sensitivity ( P>0.05) for the overall release behavior. This was attributed to the greater solubility of diltiazem hydrochloride (50% solubility in water at 25°C) in comparison to theophylline which is a sparingly soluble drug (0.85% solubility in water at 25°C). Drug release from the osmotic pump appeared to be identical under the given experimental conditions ( P>0.05). Statistical analysis of data was performed by comparing the t 50%, t 70%, t 90%; mean dissolution times (MDT 50%, MDT 70%, MDT 90%); the “difference factor, f 1” and “similarity factor, f 2”. It is concluded that the results derived from the application of the “similarity factor, f 2” are superior to the individual time points (e.g. t x %) and MDT x % values in differentiating between overall release patterns or the border line release profile differences. It also became apparent that in the case of the swellable sticking systems full surface exposure to the dissolution medium results in greater release rate. For the osmotic pump the required osmotic pressure threshold necessary for constant rate drug delivery appears to have reached independent of the hydrodynamic conditions. A successful and more accurate evaluation of dissolution data can be derived when full surface exposure is considered and this can be accomplished by dissolution method modification with the aid of the designed ring/mesh assembly.

Patterns of methane emission from excreta of grazing animals

Emissions of methane from dung pats under field and laboratory conditions have been determined. A range of dung materials from cattle and sheep and from cattle with different background managements was used and results indicated that all acted as significant sources of CH 4 over a relatively short period, usually less than 10–15 days. The patterns of release were similar, although modified by environmental conditions. A strong exponential relationship was determined between total CH 4 released and the C-to-N status of the dung, i.e. a greater rate of release with higher N status. Similar trends and patterns were displayed under controlled conditions. It was clear that the major effect came from dung itself with only a relatively small positive interaction when soil was present. Emission was stopped completely by a fumigation (chloroform)-evacuation procedure; evacuation alone (i.e. with the sample under vacuum) changed the pattern of release and increased the total amounts emitted. Although the emissions of CH 4 from dung were significant, the amounts were small relative to the estimated total release from a complete livestock production system, i.e. <0.2% of the total CH 4 output from a dairy farm.

Identification of a non-covalent oxytocin/neurophysin-I complex in the bovine ovary

Acid extracts of bovine preovulatory granulosa cells and corpora lutea (CL) were subjected to high-performance liquid chromatography (HPLC) and found to contain two peaks of immunoreactive (ir) oxytocin (OT), one corresponding to authentic OT and the second eluting 8 min later. The second peak was more abundant than authentic irOT in preovulatory follicles and in the early CL, but became less abundant as the CL matured (mid luteal) and was close to the limit of detection in the late CL. This peak could be detected only by an OT antiserum which recognized both the biologically active form of OT, as well as the post-translational processing intermediate Gly10-extended oxytocin. A second more specific OT antiserum (OT-933) did not recognize the second peak as strongly. Further analysis of the second peak revealed a complex of OT bound to its neurophysin (NP-I) which could be dissociated under denaturing conditions. Furthermore, we were able to create this complex in vitro by combining the two materials together under acid conditions, similar to the pH predicted in secretory granules, but not under neutral conditions. Measuring irNP-I by radioimmunoassay showed a single peak with a similar retention time to the OT/NP-I complex, confirming the identity of the unknown peak. Incubation of CL slices in culture showed a time-related release of both OT and NP-I, with OT having a greater rate of release in the mid luteal CL. These data suggest the presence of an OT/NP-I complex in the bovine preovulatory granulosa cells and CL, as well as the unbound peptide presumably within the secretory granules. The ratio of OT/NP-I complex and free peptide changes with ageing of the the CL, perhaps indicating regulated differences in the post-translational processing of the prohormone.

Some determinants of morphology and release rate from poly( l)lactic acid microspheres

Morphology and release rate from poly( l)lactic acid microspheres were studied as a function of drug loading, drug lipophilicity and solvent evaporation rate. Sudan III was used to exemplify lipophilic compounds, while etoposide served as a relatively polar drug. Drug loading was found to be an important determinant of morphology, with increased formation of distorted microspheres at higher loadings. In the case of the polar etoposide, this translated into a greater release rate. For Sudan III, however, negligible release occurred despite morphological changes, suggesting that the drug lipophilicity is also important as a determinant of release rate. When gelatin was used as the emulsifying agent, the percentage of distorted microspheres and the release rate were highly dependent on the rate of solvent evaporation. When smooth microspheres were produced with polyvinyl alcohol as the emulsifying agent, drying rate was found to be of less importance.

Control release of prostaglandin E2 from polylactic acid microcapsules, microparticles and modified microparticles.

Low molecular weight polylactic acid (PLA) microparticles containing prostaglandin E2 were prepared. An average particle size of 30 micron was obtained by grinding at low temperature. These particles were further treated by heating to modify the shape and the release pattern. Microscopic studies showed that the modified particles had a smoother surface than the non-modified particles. The drug was also incorporated into PLA microcapsules using the solvent evaporation process, but the incorporation efficiency was lower. We studied the release profiles of modified particles prepared using different molecular weight PLA. The release rate depended on the molecular weight with lower molecular weights having a greater release rate. In addition, the release studies showed different matrix forms made from the same molecular weight PLA had different release patterns. For example, the microcapsules released the drug very slowly whereas the modified particles exhibited a moderate release rate. It was also noted that the matrix release model could describe the release patterns of microcapsules and modified particles very well. However, the release patterns of non-modified microparticles did not follow this model.

Radionuclide Transport through Perforations in Nuclear Waste Containers

AbstractPrevious analytical models for the steady-state radionuclide release rate through perforations in nuclear waste containers into the surrounding medium, are based on a zero wall thickness assumption. In this paper we investigate the effect of the wall thickness on the mass transfer rate through isolated circular holes. We solve the steady-state diffusion equation for the concentration field and derive a model based on the analytical solution. By direct comparison, we show that the zero wall thickness model overpredicts the mass transfer rate by about 1300 percent for a circular hole with 1 cm radius and a wall thickness of 10 cm. As expected, the zero-thickness model becomes even less accurate as the hole radius decreases; it predicts a greater release rate from a large number of small holes than the mass transfer rate from an uncontained waste form cylinder. In contrast, the results predicted by our model remain bounded for isolated holes and never exceed the mass transfer from an uncontained waste form.

EFFECTS OF ATTRACTANT COMPOSITION AND RELEASE RATE ON ATTRACTION OF MALE CHORISTONEURA RETINIANA, C. OCCIDENTALS, AND C. CARNANA (LEPIDOPTERA : TORTRICIDAE)

AbstractAttraction of male Choristoneura spp. to various mixtures of the pheromone components of C. occidentalis Freeman and C. retiniana (Walsingham) released at various rates was evaluated at several sites in western North America. At all but 1 location, male trap capture increased with progressively greater release rates of a 92:8 mixture of (E)- and (Z)-11-tetradecenals (TDALs), previously identified as active components of the attractant pheromone of C. occidentalis. Similarly, trap catch was positively correlated with release rate of an 84:7:8:1 mixture of (E)- and (Z)-11-tetradecenyl acetates and (E)- and (Z)-11-tetradecenols (1:0.1 TDACs:TDOLs), previously identified as active components of the attractant pheromone of C. retiniana. All release rates of TDALs attracted only C. carnana (C. occidentalis and C. carnana probably are subspecies of the same species) in the central Sierra Nevada, but in the southern Cascades all but the lowest release rate of TDALs attracted significant numbers of males classified as C. retiniana in addition to those classified as C. occidentalis. At all locations, 1:0.1 TDACs: TDOLs exhibited complete species specificity, attracting only C. retiniana at all release rates tested. The 1:0.1 ratio of TDACs: TDOLs was the most attractive mixture of these components to C. retiniana. Addition of 1:0.1 TDACs: TDOLs did not significantly affect attraction of C. carnana to TDALs. However addition of TDALs significantly decreased attraction of C. retiniana to 1:0.1 TDACs:TDOLs.

Amino Acid Availability of Isolated Rumen Microbes as Affected by Protein Supplement

Four Angus steers weighing 450 kg were used in a 4 × 4 latin square design to study the effects of different protein supplements (corn, soybean, fish and linseed protein) on bulk ammo acid composition and amino acid availability of rumen bacteria. The effects of different protein supplements on plasma amino acids, plasma urea nitrogen, rumen volatile fatty acids and rumen ammonia were also studied. Bulk amino acid composition of rumen bacteria was not significantly (P<.05) altered by protein supplement. Availability of rumen bacterial amino acids was estimated by measuring the concentrations of amino acids released from rumen bacterial protein upon in vitro pepsin-pancreatin digestion. The release of threonine, serine, glutamic acid, valine, methionine, phenylalanine, lysine and the total amino acids released varied significantly (P<.05) among treatments. Lysine had a (P<.01) greater release rate from bacteria obtained from steers fed soybean meal than from steers fed fishmeal. Plasma leucine and aspartic acid were significantly (P<.05) affected by protein source. Rumen acetate, propionate and ammonia-nitrogen levels varied significantly (P<.05) among treatments. These data indicate that the availability of certain amino acids to the ruminant animal can vary with the source of dietary protein.