The development of pyrethroid resistance in mosquitoes threatens the goal of malaria elimination in Africa. Alternative insecticides, e.g. organophosphates, can be considered to control pyrethroid resistant mosquitoes. The problem associated with the deployment of organophosphate-based insecticides is their high volatility. Conventional application forms have a fairly short residual efficacy. This study aimed at extending the residual efficacy of an organophosphate insecticide by using a polymer matrix as a slow release device. A multilayer film blower was used to produce a trilayer film. The middle layer comprised poly(ethylene-co-vinyl acetate), i.e. EVA polymer, impregnated with malathion. This was sandwiched by two low density polyethylene (LDPE) outer layers. These acted as semi-permeable membrane-like barriers that slowed down the release of the contact insecticide to the surfaces of the film. In theory, such a film could be deployed as a long-lasting insecticide-treated wall lining in pyrethroid resistant settings. Scanning electron microscopy (SEM) confirmed the trilayer film structure of the blown film. The malathion release from the film was tracked with Fourier transform infrared spectroscopy (FTIR). The malathion absorption band in the FTIR spectra disappeared gradually over time. Confocal Raman analysis showed a malathion concentration gradient across the thickness of the polyethylene layers. These results suggested diffusion-controlled transport through the LDPE membranes. Bioassays indicated that the residual efficacy of the malathion, against mosquitoes, was increased to about six months. This means that trilayer films, impregnated with an organophosphate, may have potential as alternative mosquito control interventions in pyrethroid resistant settings. / Dissertation (MEng)--University of Pretoria, 2017. / Chemical Engineering / MEng / Unrestricted

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Stroke is a medical condition in which poor blood flow to the brain results in cell death. The current treatment options are limited and only very few patients can benefit from these treatments. Stroke causes brain swelling and often a decompressive craniectomy is performed for some of the patients to release intracranial pressure to prevent further damage. As a result, a duraplasty is implanted to replace the surgically-damaged dura mater to protect the brain. In view of that, the purpose of this project was to develop double-walled microspheres (DWMS) which can be used as a drug delivery system when incorporated into duraplasty to promote endogenous stem cell therapy to treat stroke. The DWMS were composed of poly (l-lactic acid) (PLLA) and poly (lactic-co-glycolic acid) (PLGA) using a solvent evaporation method. Bovine serum albumin (BSA), as a model protein, was entrapped within these DWMS with different core-shell thicknesses and compositions to investigate the distribution of protein, encapsulation efficiency, and in vitro release. The fabrication process parameters of DWMS were also optimized to attain higher yields, and the phase separation and surface morphology were examined by differential scanning calorimetry and scanning electron microscopy.

The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued to guarantee the controlled release of cargo at a specific time and with an accurate amount. Upon applying different stimuli such as light, magnetic field, heat, pH change, enzymes or redox, functional materials change their physicochemical properties through physical transformation or chemical reactions, allowing the release of payload agents on demand. This dissertation studied three stimuli-responsive membrane systems for controlled release from films of macro sizes to microcapsules of nano sizes. The first membrane system is a polymeric composite film which can decrease and sustain diffusion upon light irradiation. The photo-response of membranes is based on the photoreaction of cinnamic derivatives. The second one is composite membrane which can improve diffusion upon heating. The thermo-response of membranes comes from the volume phase transition ability of hydrogels. The third one is microcapsule which can release encapsulated agents upon light irradiation. The photo-response of capsules results from the photoreaction of nitrobenzyl derivatives. The study on these membrane systems reveals that stimuli-responsive release can be achieved by utilizing different functional materials on either macro or micro level. Based on the abundant family of smart materials, designing and fabricating stimuli-responsive systems shall lead to various advanced release processes on demand for biomedical applications.

Climent Terol, E. (2012). Design of new hybrid materials: Study of its application in new detection formats and in controlled release applications [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17939 / Palancia

The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [ H]NE uptake via the NET and simultaneously increased [ H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca . Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [ H]NE uptake but did not block KCl-stimulated increases in [ H]NE uptake. In contrast, PMA increased [ H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca -activated signaling cascades with KN93 (a Ca calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [ H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [ H]NE release. KCl-stimulated increases in [ H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca , different intracellular mechanisms mediate these two events.

<p>  </p> <p>This dissertation investigated the influence of formulation and process design on the internal density structure and nutrient release of urea fertilizer as an alternate route to overcome nutrient leaching problems. The first part of the work focused on producing urea composites with different binders to optimize the formulation and composite microstructure. The second part of the study compared the microstructure and release kinetics of dry compacted and bilayer urea granules. Finally, the third part determined nitrate and ammonium leaching using disturbed soil column experiments. The optimization of granule microstructure and formulation design developed in this work yielded a 97.5 % reduction in the initial dissolution rate of modified urea granules compared to conventional urea fertilizer. Thus, the development of processing platforms focused on granule internal density distributions demonstrated a fundamental contribution to optimizing nutrient release properties.</p>

Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with α-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 ± 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey.

Antibody microprobes were used to study release of immunoreactive neurokinins in the dorsal horn of the anaesthetized spinal cat following sustained isometric contraction of ipsilateral hindlimb muscles. Microprobes had immobilized antibodies to neurokinin A (NKA) on their outer surfaces and bound a proportion of released molecules when inserted in the central nervous system. Bound molecules were detected in autoradiographs as zones of reduced binding of 125I-NKA in which microprobes were incubated after withdrawal from the spinal cord. The left hindlimb was immobilized using an epoxy bandage splint and isometric contraction of muscles induced by intermittent tetanic stimulation of a ventral root. A basal presence of immunoreactive neurokinins was detected and this was increased by sustained isometric muscle contraction. It is probable that ergoreceptors contain and release neurokinins.

Advances in molecular medicine have produced a large amount of information about genes that translate to therapeutic molecules when expressed in living cells. There is an increasing interest in nonviral methods for gene delivery, to address all concerns on non-toxic, easy, and possibly efficient delivery systems. In this paper we introduced a new attractive approach for non-viral transferring of genetic materials on demand. By using lipofectin reagent (1:1 molar ratio of DOPE:DOTMA. DOPE: L-α-doleoyl posphatidylethanolamine; DOTMA: N-[1-(2,3-dideyloxy) propyl]-n,n,n-trimethylammonium chloride), the lipid/DNA complexes (lipoplexes) can be electrostatically adsorbed on the gold microelectrode surface. The resulting lipoplexes molecules can be subsequently removed from the surface by applying -1.0 V (vs. Ag/AgCl) in physiological phosphate buffer medium (pH 7.4). This electrochemically controlled-release process has been extensively examined by gel electrophoresis (GE), electrochemical quartz crystal microbalance (EQCM), infrared spectroscopy (IR), and square wave voltammetry (SWV) techniques. The lipoplex composition has been addressed for efficient gene delivery protocol, based on their different charge ratios. The results from different techniques coincided, as also verified by the repetitive control experiments. This in-vitro electrically - triggered release protocol for genetic material offers the current gene delivery arsenal a new, simple, and non-viral alternative.