Active Release Mechanism Research Articles

Sources and Methods for the Production of Xyloglucan, a Promising Stimulus-Sensitive Biopolymer: A Review

Xyloglucan is a highly promising ‘green’ polymer that has found its application in the food and pharmaceutical industries. Due to its molecular structure similarity to mucin, it has remarkable mucoadhesion properties, which has led to a high research interest in this excipient for the development of transmucosal delivery systems. Thermosensitivity is another promising property of xyloglucan derivatives, which is mainly exhibited by synthetic block copolymers such as pluronics and PLGA derivatives. Delivery systems whose mechanism of active ingredient release is based on temperature sensitivity are widely used in many medical fields, ranging from antitumour therapy to intranasal delivery. Thus, conducting research on the possibility of obtaining and using a new mucoadhesive, fully biocompatible and affordable polymer—xyloglucan—is a promising task.

Assessing the benefits of real-time control to enhance rainwater harvesting at a building in Cape Town, South Africa

In the period 2015–2017, the City of Cape Town, South Africa, faced the possibility of taps running dry due to a prolonged drought. To mitigate the impacts of water scarcity, many households installed rainwater tanks to harvest water to use for non-potable purposes such as toilet flushing and washing. The installation of the rainwater tanks was mainly arbitrary, in response to perceived impact of water scarcity rather than a systematic needs assessment. This study was thus undertaken to determine the available opportunity to optimise the use of these rainwater tanks using real-time control (RTC) techniques. Many studies have demonstrated the potential of rainwater harvesting (RWH) systems to supplement potable water supply and minimize stormwater flows to downstream drainage networks. RTC technology can be used to enhance the performance of RWH systems in achieving these two objectives, by receiving a rainfall forecast and initiating pre-storm release in real time. In this study, RTC was applied on the RWH system at the New Engineering Building, University of Cape Town (UCT) to enhance water supply and increase rainwater retention period. The performance with RTC was compared with the conventional management of the RWH system. It was determined that RWH with RTC technology was generally superior in simultaneously achieving water supply and rainwater retention benefits compared to the conventional management approach. RTC provides an active operation which optimizes the performance of the system across varying conditions but requires an assiduous management process designed to meet set objectives. It was concluded that the active release mechanism employing RTC exhibited great potential; the system opens up the possibility of delivering a more robust and reliable system due to its ability to provide failure detection and centralised control. The system can readily be adapted to variation of local climatic conditions in the short and long term.

Seeing Is Believing: Time-Lapse Macro-Imaging of Morphological Changes of Solid Dosages as a Teaching and Research Tool.

Disintegration kinetics and behaviors are critical for the quality and performance of oral solid dosages. Instead of performing standard disintegration tests, herein, we aim to visualize these kinetic processes in real time. A visual acquisition system is developed to capture the morphological changes of tablets under static conditions via time-lapse macro-imaging. The system consists of: i) a customized quartz chamber, ii) a metal sieve with pore sizes ranging from 1 to 2mm in diameter to allow rapid settling of the disintegrated particles, and iii) a temperature-controlled water bath. A typical workflow consists of the following steps: i) planning of the experiment to consider the type of the active pharmaceutical ingredient and drug release mechanism; ii) acquisition of photo-imaging data from at least two cameras arranged at different angles over a predetermined time period; iii) post-processing of the image data; iv) production of video clips and image analysis. Representative works are shown to demonstrate the disintegration phenomenon or the morphological changes of solid drug products of various controlled- and extended-release mechanisms. These video clips are used as teaching materials for students majoring in pharmacy or pharmaceutical chemistry, which also provide an insightful unique perspective of the microprocess during tablet fragmentation, disintegration or drug release.

Medical Microrobot — A Drug Delivery Capsule Endoscope with Active Locomotion and Drug Release Mechanism: Proof of Concept

This paper presents a robotic capsule endoscope integrated a targeted drug delivery module (DDM) for digestive diseases treatments. The capsule with a big permanent magnet inside is wirelessly controlled and actively moves to target region in gastrointestinal tract by an electromagnetic actuation system (EMA). DDM is a separated body composed of a drug container and a non-power drug-releasing mechanism. The force to expel drug is generated by carbon dioxide gas pressure coming from a chemical reaction inside a propellant reservoir. Where the chemical reaction is activated by a mechanical mechanism that allows dry chemical powders contacting with water at the target point. A small permanent magnet is utilized to separate reagents and wet paper before drug injection. It is designed to be stable during locomotion by virtue of the attractive force of a big permanent magnet. To trigger releasing mechanism, gradient magnetic field from EMA system is created to push small magnet slide down, which allows reagents drop and contact with water in wet paper. The designed DDM has length of 11 mm and diameter of 11 mm. The proposed robotic capsule could show high potentials to be utilized for therapeutic treatment of digestive diseases in practical clinical sites through simulation and ex-vivo experiments.

Soy-Based Soft Matrices for Encapsulation and Delivery of Hydrophilic Compounds.

A new controlled-release platform for hydrophilic compounds has been developed, utilizing citric acid-cured epoxidized sucrose soyate (ESS) as the matrix forming material. By cross-linking epoxy groups of ESS with citric acid in the presence of a hydrophilic model molecule, sodium salt of fluorescein (Sod-FS), we were able to entrap the latter homogenously within the ESS matrix. No chemical change of the entrapped active agent was evident during the fabrication process. Hydrophobicity of the matrix was found to be the rate-limiting factor for sustaining the release of the hydrophilic model compound, while inclusion of release-modifiers such as poly(ethylene glycol) (PEG) within the matrix system modulated the rate and extent of guest release. Using 5 kDa PEG at 5% w/w of the total formulation, it was possible to extend the release of the active ingredient for more than a month. In addition, the amount of modifiers in formulations also influenced the mechanical properties of the matrices, including loss and storage modulus. Mechanism of active release from ESS matrices was also evaluated using established kinetic models. Formulations composed entirely of ESS showed a non-Fickian (anomalous) release behavior while Fickian (Case I) transport was the predominant mechanism of active release from ESS systems containing different amount of PEGs. The mean dissolution time (MDT) of the hydrophilic guest molecule from within the ESS matrix was found to be a function of the molecular weight and the amount of PEG included. At the molecular level, we observed no cellular toxicities associated with ESS up to a concentration level of 10 μM. We envision that such fully bio-based matrices can find applications in compounding point-of-care, extended-release formulations of highly water-soluble active agents.

Squeezing release mechanism of encapsulated compounds from photo-sensitive microcapsules

Controlled release of photo-triggered systems is widely investigated due to its enormous functional applications, but only a few reports describing a mechanism of this phenomenon have been published. To provide a mechanism of active material release from photo-sensitive microcapsules based on cross-linked liquid crystalline polyamide containing azobenzene moieties incorporated in the main chain, we performed quantum chemical calculations. By optimizing structure of trans and cis isomers of azobenzene molecule we were able to show that its trans-to-cis isomerization is responsible for release of encapsulated material. Computational investigation demonstrated that the polymeric main chain length forming the capsule shell decreases approximately 28% in comparison to the initial state by trans–cis isomerization of azobenzene moieties. Moreover, the photo-isomerization of azobenzene molecules was experimentally confirmed by Fourier Transform Infrared Spectroscopy (FTIR) and its influence on capsule morphology was monitored by Atomic Force Microscopy (AFM). Finally, based on theoretical and experimental data a mechanism of encapsulated active release from capsule shells was proposed.

Improving the Multi-Objective Performance of Rainwater Harvesting Systems Using Real-Time Control Technology

Many studies have identified the potential of rainwater harvesting (RWH) systems to simultaneously augment potable water supply and reduce delivery of uncontrolled stormwater flows to downstream drainage networks. Potentially, such systems could also play a role in the controlled delivery of water to urban streams in ways which mimic baseflows. The performance of RWH systems to achieve these three objectives could be enhanced using Real-Time Control (RTC) technology to receive rainfall forecasts and initiate pre-storm release in real time, although few studies have explored such potential. We used continuous simulation to model the ability of a range of allotment-scale RWH systems to simultaneously deliver: (i) water supply; (ii) stormwater retention; and (iii) baseflow restoration. We compared the performance of RWH systems with RTC technology to conventional RWH systems and also systems designed with a passive baseflow release, rather than the active (RTC) configuration. We found that RWH systems employing RTC technology were generally superior in simultaneously achieving water supply, stormwater retention and baseflow restoration benefits compared with the other types of system tested. The active operation provided by RTC allows the system to perform optimally across a wider range of climatic conditions, but needs to be carefully designed. We conclude that the active release mechanism employing RTC technology exhibits great promise; its ability to provide centralised control and failure detection also opens the possibility of delivering a more reliable rainwater harvesting system, which can be readily adapted to varying climate over both the short and long term.

Nontypeable Haemophilus influenzae releases DNA and DNABII proteins via a T4SS-like complex and ComE of the type IV pilus machinery

Biofilms formed by nontypeable Haemophilus influenzae (NTHI) are central to the chronicity, recurrence, and resistance to treatment of multiple human respiratory tract diseases including otitis media, chronic rhinosinusitis, and exacerbations of both cystic fibrosis and chronic obstructive pulmonary disease. Extracellular DNA (eDNA) and associated DNABII proteins are essential to the overall architecture and structural integrity of biofilms formed by NTHI and all other bacterial pathogens tested to date. Although cell lysis and outer-membrane vesicle extrusion are possible means by which these canonically intracellular components might be released into the extracellular environment for incorporation into the biofilm matrix, we hypothesized that NTHI additionally used a mechanism of active DNA release. Herein, we describe a mechanism whereby DNA and associated DNABII proteins transit from the bacterial cytoplasm to the periplasm via an inner-membrane pore complex (TraC and TraG) with homology to type IV secretion-like systems. These components exit the bacterial cell through the ComE pore through which the NTHI type IV pilus is expressed. The described mechanism is independent of explosive cell lysis or cell death, and the release of DNA is confined to a discrete subpolar location, which suggests a novel form of DNA release from viable NTHI. Identification of the mechanisms and determination of the kinetics by which critical biofilm matrix-stabilizing components are released will aid in the design of novel biofilm-targeted therapeutic and preventative strategies for diseases caused by NTHI and many other human pathogens known to integrate eDNA and DNABII proteins into their biofilm matrix.

Clinical Vagus Nerve Stimulation Paradigms Induce Pronounced Brain and Body Hypothermia in Rats

Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimer's disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around [Formula: see text]C, while standard cycle VNS (30[Formula: see text]s on/300[Formula: see text]s off) was associated with a decrease of around [Formula: see text]C. Rectal temperature similarly decreased by more than [Formula: see text]C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.

In Vivo Efficacy of a “Smart” Antimicrobial Implant Coating

Postoperative infection is a devastating complication following arthroplasty. The goals of this study were to introduce a "smart" implant coating that combines passive elution of antibiotic with an active-release mechanism that "targets" bacteria, and to use an established in vivo mouse model of post-arthroplasty infection to longitudinally evaluate the efficacy of this polymer implant coating in decreasing bacterial burden. A novel, biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics both passively and actively. In vitro-release kinetics were studied using high-performance liquid chromatography (HPLC) quantification in conditions representing both the physiologic environment and the more oxidative, hyperinflammatory environment of periprosthetic infection. The in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline was tested using an established mouse model of post-arthroplasty infection. Noninvasive bioluminescence imaging was used to quantify the bacterial burden; radiography, to assess osseointegration and bone resorption; and implant sonication, for colony counts. In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a "smart" active-release mechanism. The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). A mean of 0, 9, and 2.6 × 10(2) colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 10(2), 4.3 × 10(3), and 5.9 × 10(4) CFUs, respectively, on culture of the surrounding tissue (p < 0.05). The PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study. PEG-PPS polymer provides a controlled, "smart" local delivery of antibiotics that could be used to prevent postoperative implant-related infections.

Air humidity thresholds trigger active moss spore release to extend dispersal in space and time

Summary Understanding the complete dispersal process is important for making realistic predictions of species distributions, but mechanisms for diaspore release in wind‐dispersed species are often unknown. However, diaspore release under conditions that increase the probability of longer dispersal distances and mechanisms that extend dispersal events in time may have evolutionary advantages. We quantified air humidity thresholds regulating spore release in the moss Brachythecium rutabulum. We also investigated the prevailing micrometeorological conditions when these thresholds occur in nature and how they affect dispersal distances up to 100 m, using a mechanistic dispersal model. We show that moss spores were mainly released when the peristome teeth were opening, as relative air humidity (RH) decreased from high values to relatively low (mainly between 90% and 75% RH). This most often occurred in the morning, when wind speeds were relatively low. Surprisingly, the model predicted that an equally high proportion of the spores would travel distances beyond 100 m (horizontally) when released in the wind conditions prevailing during events of RH decrease in the morning, that lead to peristome opening, as in the highest wind speeds. Moreover, a higher proportion of the spores reached high altitudes when released at the lower wind speeds during the morning compared to the higher speeds later in the day, indicating a possibility for extended dispersal distances when released in the morning. Dispersal in the morning is enhanced by a combination of a more unstable atmospheric surface layer that promotes vertical dispersal, and a lower wind speed that decreases the spore deposition probability onto the ground, compared to later in the day. Our study demonstrates an active spore release mechanism in response to diurnally changing air humidity. The mechanism may promote longer dispersal distances, because of enhanced vertical dispersal and because spores being released in the morning have more time to travel before the wind calms down at night. The mechanism also leads to a prolonged dispersal period over the season, which may be viewed as a risk spreading in time that ultimately also leads to a higher diversity of establishment conditions, dispersal distances and directions.

Eudragit FS 30D as a potential polymer for use in the technology of preparing matrix tablets contain metronidazole – an experimental and mathematical modeling study

Abstract The aim of this study was to examine the usefulness of a pH-dependent copolymer - Eudragit FS - for employment in the technology of preparing modified release metronidazole matrix tablets. In addition, in our work, Eudragit RL and Eudragit RS were included in the composition of some formulations, as well as sodium lauryl sulfate and polysorbate 80. As part of the study of the dissolution test, the similarity coefficient (f2) for the obtained profiles was calculated, and mathematic models were used to estimate the kinetics and mechanism of active substance release. In our work, it was observed that the inclusion of polymer Eudragit FS alone in the tablet composition ensured a modified release of the active substance for 10 h. After this time period, the amount of metronidazole determined in the acceptor fluid was 71% - 81% of the declared dose. Modification of the composition by the addition of surfactants resulted in an increased release of the active substance of up to 98%. This effect was dependent on the type of surfactant and its quantitative ratio to the Eudragit FS. Similar release profiles were obtained for tablets containing Eudragit RS and sodium lauryl sulfate, as well as Eudragit RS and polysorbate 80. Depending on the composition of tablets, metronidazole release proceeded in accordance with either first or second-order kinetics. We calculated as well, that the differing masses of Eudragit FS in the studied formulations correlates with the order of release kinetics (p &lt; 0.002). Such an effect was validated using the Weibull model, wherein, in all the studied formulations, the release rate was seen as a decreasing function of time. An analysis of data according to the Ritger-Peppas model and the Peppas-Sahlin model for some formulations, indicated that the mechanism of active substance release from matrix tablets is diffusion.

Encapsulation of alendronate sodium by nanoprecipitation and double emulsion: From preparation to in vitro studies

Alendronate sodium is an active molecule indicated as first line regimen for osteoporosis treatment. Use of this drug presents, however, some shortcomings such as low oral bioavailability and gastrointestinal mucosa irritation. Nanotechnology remains an attractive approach to overcome such limitations of conventional pharmaceutical forms. However, encapsulation of hydrophilic molecules like alendronate represents a real challenge. Preparation, characterization and drug release behavior of polycaprolactone based nanoparticles loaded with alendronate sodium were investigated in this work. Two strategies were used to prepare these nanocarriers: double emulsion evaporation and nanoprecipitation. Operating conditions were monitored to produce biocompatible nanoparticles with good properties. Both techniques gave nanoparticles with mean diameter in the range of 200–450nm. Encapsulation efficiency of selected formulae reached 34% for double emulsion and 18% for nanoprecipitation, respectively. Highest drug loading was 20.7% for double emulsion and 8.2% for nanoprecipitation, respectively. For both methods, an increase of polymer molecular weight and polymer amount led to an increase of particle size. For nanoprecipitation, oil to water phase exerted also a significant effect on particle size. The increase of stabilizer amount or the use of rotoevaporation rather than continuous stirring at ambient temperature decreased particles size. Prepared nanoparticles exhibited sustained release of alendronate. When the same polymer amount and molecular weight was used, drug release of the selected formulae was faster for nanoparticles formulated by the nanoprecipitation method. However, release profiles were similar for both techniques with a first rapid release phase followed by a more prolonged phase. Analysis of in vitro release data showed also that active release mechanism relied on a combination of drug diffusion and polymer relaxation phenomena.

Polymer Microcapsules with Programmable Active Release

We present a new type of microcapsule programmed with a tunable active release mechanism. The capsules are triggered by a plasticizing stimulus that induces a phase change transition of the polymeric membrane from a solid to a fluidized form; thereafter, the cargo is actively driven out of the capsule through a defect at the capsule wall with controllable release kinetics. Tuning the degree of membrane fluidity by tailoring the amount of plasticizing stimulus present allows us to obtain temporal variation of the release kinetics from a subsecond abrupt burst release to a slow sustained release of encapsulant over many minutes. Moreover, we demonstrate tuning of the collective capsule triggering response by adjusting stimulus content, polymer molecular weight, and capsule membrane thickness. For this model system, we use a microfluidic approach to fabricate polystyrene capsules triggered by a toluene stimulus. However, this active release approach is general and is applicable to diverse polymeric capsule systems; this versatility is demonstrated by extension of our trigger-release scheme to capsules fabricated from a rubberlike block copolymer. The utility of our technique further enhances the potential of these active release capsules for practical application.

Mercury in fishes from Augusta Bay (southern Italy): Risk assessment and health implication

Our study reports on the total mercury (HgT) concentrations measured in the muscles and livers of several benthic, demersal and pelagic fish species caught inside and outside of Augusta Bay (southern Italy), a semi-enclosed marine area, highly contaminated by the uncontrolled (since the 1950s to 1978s) discharge of the largest European petrochemical plant. Mercury levels in fish tissues are discussed with regard to specific habitat, size and/or age of the specimens and HgT distribution in the bottom sediments. Results suggest a still active Hg release mechanism from the polluted sediments to the marine environment. Also, the high HgT concentrations measured in fishes caught in the external area of the bay imply a potential role of Augusta Bay as a pollutant source for the Mediterranean ecosystem. Finally, values of hazard target quotient (THQ) and estimated weekly intake (EWI) demonstrate that consumption of fishes caught inside the bay represents a serious risk for human health. Also, data indicate that intake of fishes caught from the external area of the bay, especially for that concern demersal and benthic species, could be represent a significant component of risk for the local population.

Circulating Cell-Free DNA

The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

Injectable Thermally Responsive Mucoadhesive Gel for Sustained Protein Delivery

Poloxamer thermoresponsive gels are widely explored in controlled drug delivery. Nevertheless, these gels possess inadequate mechanical properties, poor bioadhesiveness, and high permeability to water. To overcome these issues, we blended mucoadhesive hyaluronic acid (HA) with poloxamer analogs. This study aimed to investigate the features affecting the microscopic properties of the gels, which determine their macroscopic properties and capability to control/sustain protein release. Results showed that HA hampers water-poloxamer interactions, thus, strongly influencing physicochemical properties of poloxamer gels. This leads to gels with improved mechanical properties in which the diffusion kinetics of macromolecular active molecules are drastically slowed down. Poloxamer-HA gels can sustain the delivery of proteins, such as insulin, and may allow the modulation of its release kinetics by modifying HA content within the gels in the administration sites in which the active molecule release mechanism is mainly governed by its diffusion.

Kinetic and Structural Modeling Mechanisms of Melatonin Transport from an Electrolytically Regulated Salted-out PLGA Scaffold

This study focused on optimizing the mechanism of zero-order active pre-programmed release of melatonin from a salted-out PLGA scaffold. A Box—Behnken design, modeled the formulations, required for optimizing the melatonin entrapment efficiency (EE), mean dissolution time at 30 days (MDT30) and the release rate constant ( k). Response Surface Methodology depicted the influence of NaCl, CaCl2, and AlCl3 on the release kinetics. Qualitative structural kinetic modeling and quantitative mathematical modeling of release data supported the kinetic events, interaction parameters, and melatonin transport phenomena that resolved the constraints governing the rate and extent of melatonin release. A salted-out PLGA chain was evaluated by rheological studies and braided rope-coiling and nonbraided nonrope coiling with dynamic simulations capturing the coherent structural transitions in the turbulent release medium with the influence of salts on the swelling or erosion, energy dissipation, and subsequent melatonin release. The release was mainly governed by erosion and not affected by time-dependent diffusion resistance (Hopfenberg model; n = 0.95; R2 = 0.96; ke = 0.11—4.69×10-3mm/min; D = 0.110—0.893 × 10 -8 cm2/s; Debrelease = 0.016—1.312). Swelling parameters confirmed that polymer swelling did not significantly influence melatonin release (δ = 0.232.00 mm, v = 0.027—0.181 cm/s, S w = 0.010—0.542). EE values ranged between 46% and 90% and were dependant on the salt type and concentration. AlCl3 and NaCl blends increased the k values (0.0050) indicating their significance in melatonin release. The optimal scaffold (EE = 95%; MDT30 = 1; k = 0.0050) was predicted to comprise 1.1451 and 0.8264 w/v of NaCl and AlCl3, respectively, with the exclusion of CaCl2 in order to achieve zero-order kinetics over 30 days. The kinetic modeling approach enabled a qualitative and quantitative description of melatonin release patterns from the salted-out PLGA scaffolds thus facilitating the manipulation and prediction of drug release from PLGA modification by salting-out.

Extracellular plasma RNA from colon cancer patients is confined in a vesicle-like structure and is mRNA-enriched

Little is yet known about the origin and protective mechanism of free nucleic acids in plasma. We investigated the possibility of these free nucleic acids being particle associated. Plasma samples from colon cancer patients and cell culture media were subjected to various antibody incubations, ultracentrifugation, and RNA extraction protocols for total RNA, epithelial RNA, and mRNA. Flow cytometry using a Ber-EP4 antibody and confocal laser microscopy after staining with propidium iodide were also performed. mRNA levels of the LISCH7 and SDHA genes were determined in cells and in culture media. Ber-EP4 antibody and polystyrene beads coated with oligo dT sequences were employed. We observed that, after incubation, total RNA and mRNA were always detected after membrane digestion, and that epithelial RNA was detected before this procedure. In ultracentrifugation, mRNA was caught in the supernatant only if a former lysis mediated or in the pellet if there was no previous digestion. Flow cytometry determinations showed that antibody-coated microbeads keep acellular structures bearing epithelial antigens apart. Confocal laser microscopy made 1- to 2-microm-diameter particles perceptible in the vicinity of magnetic polystyrene beads. Relevant differences were observed between mRNA of cells and culture media, as there was a considerable difference in LISCH7 mRNA levels between HT29 and IMR90 cell co-cultures and their culture media. Our results support the view that extracellular RNA found in plasma from cancer patients circulates in association with or is protected in a multiparticle complex, and that an active release mechanism by tumor cells may be a possible origin.

Isothermal kinetics of (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid release from a poly(acrylic acid‐co‐methacrylic acid) hydrogel

AbstractA kinetic study of the release of the drug (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid (MEPBA) from a poly(acrylic acid‐co‐methacrylic acid) (PAA‐co‐MA) hydrogel was performed. The isothermal kinetic curves of MEPBA release from the PAA‐co‐MA hydrogel in bidistilled water at different temperatures ranging from 20 to 40°C were determined. The reaction rate constants of the investigated process were determined with the initial rate, the saturation rate, and Peppas's semiempirical equation. Also, a model‐fitting method for the determination of the kinetics model of drug release was applied. The influence of α at the values of the kinetic parameters and the presence of a compensation effect was established. A procedure for the determination of the distribution function of the activation energies was developed. This procedure was based on the experimentally determined relationship between the activation energy and α. The mechanism of active compound release is discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008