A Cationic Polymeric Alcohol Anti-Sloughing Agent and its Mechanisms

A cationic polymeric alcohol anti-sloughing agent YPVA with well anti-sloughing function and lower side effect of increasing viscosity was developed through modifying the polymeric alcohol (PVA). Degrade PVA firstly, then make the degraded PVA have action groups. It was proved that the modified PVA has ortho-nitrogen radicals by molecular structure analysis through infrared spectrum. Then the anti-sloughing mechanisms of YPVA were investigated deeply through experiments such as rolling and dispersing recovery, zeta potential and particle size distribution measuring, adsorption and pressure transmission. The anti-sloughing mechanisms are mainly as follows: prevent mud shale particles to hydrate and disperse by adsorbing and coating; holdback mud shale particles to hydrate through altering their surface charge and compressing their diffused double layer after adsorbing on them; pressure and block filtrate transfer through forming film and covering on the surface of slits and pores after adsorbing on the surface of rock in the stratum

Development of In vitro Multi-Species Biofilms to Explore Strategies to Prevent Biofilm-Associated Oral Diseases

More than 80% of infectious diseases are caused by microbial biofilms. In the oral cavity, biofilms are composed of hundreds of distinct bacteria. The accumulation of oral biofilms can lead to caries and periodontal disease. From a public health standpoint, the cost of treatment for oral diseases remain high, at over $100 billion dollars per year in US alone. The primary aim of this project was to evaluate new anti-biofilm agents using novel in vitro biofilm model systems. In addition, the biology of oral biofilms and their relationship to oral diseases are discussed in the context of their development in laboratory biofilm model systems. Nisin is a unique bacteriocin generated by a group of Lactococcus and Streptococcus species. The objective of the first part of the work was to determine if nisin exhibited broad-spectrum antimicrobial effects against oral bacteria. In addition, the presented work showed that nisin inhibited the growth and maintenance of saliva derived biofilms developed in static and controlled-flow biofilm model systems. Even at higher concentrations, nisin did not exhibit cytotoxic effects on human oral cells. L-arginine is an amino acid that is present in low levels in the oral cavity. At lower concentrations, L-arginine is a nutrient source for arginolytic bacteria. The objective of the second part of the work was to explore the short-term effects of high concentrations of L-arginine on oral biofilms. A modified Swinnex model system was used to develop the multi-species oral biofilms and the FlowCam® was used to monitor the biofilm dispersion. In a dose-dependent manner, L-arginine treatment resulted in biofilm destabilization through enhanced biofilm dispersion. Based on community analyses of the biofilms and the dispersed cells, L-arginine did not result a significant shift in the community compared to the water-treated controls. In summary, the work presented in this thesis demonstrated that complex biofilms, that contain species present in the human oral cavity, can be developed using three different in vitro biofilm model systems. In addition, we showed that nisin and L-arginine has high potential to disrupt the in vitro developed multi-species biofilms and these compounds have potential as novel anti-biofilm agents.PHDOral Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138465/1/jaemshin_1.pd

The Production and Application of Hydrogels for Wound Management: A Review

Wound treatment has increased in importance in the wound care sector due to the pervasiveness of chronic wounds in the high-risk population including, but not limited to, geriatric population, immunocompromised and obese patients. Furthermore, the number of people diagnosed with diabetes is rapidly growing. According to the World Health Organization (WHO), the global diabetic occurrence has increased from 4.7 in 1980 to 8.5 in 2014. As diabetes becomes a common medical condition, it has also become one of the major causes of chronic wounds which require specialised care to address patients’ unique needs. Wound dressings play a vital role in the wound healing process as they protect the wound site from the external environment. They are also capable of interacting with the wound bed in order to facilitate and accelerate the healing process. Advanced dressings such as hydrogels are designed to maintain a moist environment at the site of application and due to high water content are ideal candidates for wound management. Hydrogels can be used for both exudating or dry necrotic wounds. Additionally, hydrogels also demonstrate other unique features such as softness, malleability and biocompatibility. Nowadays, advanced wound care products make up around 7.1 billion of the global market and their production is growing at an annual rate of 8.3 with the market projected to be worth 12.5 billion by 2022. The presented review focuses on novel hydrogel wound dressings, their main characteristics and their wound management applications. It also describes recent methodologies used for their production and the future potential developments

The use of hydrogels to prevent biofouling on underwater sensors

The biofouling resistant coatings of hydrogel containing the cationic surfactants benzalkonium chloride and Arquad 2C-75 both extended the fouling free period in marine temperate waters. In the case of BAC the coating stayed clean for 10-12 weeks and the Arquad 2C-75 for 12-14 weeks. Due to the longer life of the hydrogel containing the Arquad 2C-75 instrument trials were carried out using this material. An effective method of attaching the coatings to the optical and membrane ports of sensors was developed and allows the coating to be either held in either a screw down or bolted polymer ring. The diffusion coefficient of cationic surfactants in seawater is reduced compared to diffusion coefficients in freshwater. In seawater the diffusion coefficient of benzalkonium chloride was found to be 2.44 x 10-6 cm2 s-1 compared to 7.78 x 10-6 cm2 s-1 in distilled water at 25°C. Careful choice of gas permeable membrane can result in a slightly longer biofouling lifetime, but only by 1-2 weeks. At 6 weeks all gas permeable membranes had significant fouling which affected their gas permeability. The diffusion rates of ammonia gas, a gas commonly measured in the sea, through PTFE gas sensor membranes varied between PTFE manufacturers with flux measurements ranging from 0.05-1131 µg cm-2 h-1. In addition to the hydrogel testing on instruments within this project a variety of external research groups and environmental agencies are currently testing the hydrogels on their instrumental ports

Doctor of Philosophy

dissertationPoly(amido amine) (PAMAM) dendrimers have shown potential to carry poorly absorbed drugs across the intestinal barrier and into systemic circulation, reducing the need for intravenous injections. Much of the in vitro transepithelial transport of PAMAM dendrimers to date has been investigated using Caco-2 monolayers which lack the microvilli morphology and enzymes present in isolated intestinal tissues. In addition, a challenge in predicting oral absorption is establishing a correlation between transport across rodent and human intestinal tissues. This dissertation focused on investigating the transepithelial transport of PAMAM dendrimers across rat and human isolated intestinal tissues. Permeability values in isolated tissues were compared with those across Caco-2 cell monolayers. Results indicate a difference in transport of PAMAM dendrimers, morphological changes and transepithelial electrical resistance between Caco-2 cell monolayers, rat and human intestinal tissue models. A relatively high transport rate across the tissues, given the macromolecular nature of PAMAM dendrimers, shows promise for use of these constructs for oral delivery in human

Bioadhesive Microparticles and Liposomes of Anti-Parkinson Drugs for Nasal Delivery

The nasal route is highly promising for the delivery of drugs exerting local effects in the nose or for therapeutic molecules having systemic or CNS effect. This is attributed to the fact that the nasal epithelium is highly vascularized and permeable, which ensures rapid absorption of the drug. The limitation of short residence time of the formulations in the nose and poor bioavailability of hydrophilic drugs could be overcome by the inclusion of bioadhesive agents into formulation. The main objective of this study was to develop novel bioadhesive microspheres and liposomes entrapping the anti-Parkinson drugs ropinirole hydrochloride (RH). The microspheres were prepared via spray drying in combination with chitosan or sodium alginate and the liposomes were prepared using the ethanol-based proliposome method. This study has investigated the potential of powdered mucoadhesive microparticles and liquid liposomes for nasal delivery via Miat® nasal insufflator and nasal spray devices respectively. Optimum mucoadhesive chitosan microparticles were prepared by co-spray drying of chitosan glutamate and ropinirole hydrochloride (90:10 w/w). Characterization studies have revealed that the drug following spray drying was amorphous and the microparticles were spherical and offered drug entrapment efficiency values in the range of 93 - 99%. The optimum formulation provided maximum swelling capacity and slowest drug release. Ex vivo toxicity study using isolated sheep nasal mucosa proved the safety of the optimized formulations for intranasal delivery. Investigation of powder delivery demonstrated that the Miat® nasal insufflator could deliver 90% of the dose with the first puff regardless of the loading weight used to fill the capsule fitted into the nasal device. The spray cloud had elongated shape and was homogenous; this is expected to enhance the impaction of the formulation in the nose following delivery from the nasal device. The properties of sodium alginate microparticles prepared via spray drying were highly dependent on inlet temperature of the spray drier, affecting particle morphology and product yield percent. The best performing particles were obtained when the inlet temperature was 140oC. Alginate to RH ratio had marked effect on particle size (2.60 - 4.37µm), entrapment efficiency (101 – 109%), physical state of the encapsulated RH, and morphology and surface smoothness of the particles as shown by scanning electron microscopy (SEM). In vitro drug release profile showed the amount of sodium alginate in formulations has controlled the rate of drug release. Results revealed that RH-alginate microparticles in 90:10 w/w polymer to drug ratio was the best performing spray dried formulation. Toxicity study proved safety of RH loaded sodium alginate for intranasal delivery. In contrast to RH-chitosan microparticles, particle trajectories was found from the cloud generated from emitted powder and laser diffraction demonstrated that powder was less likely to deposit in the lower respiratory tract owing to particle agglomeration. Ethanol-based proliposome technology produced oligolamellar liposomes from lipid ethanolic solutions as revealed by transmission electron microscopy (TEM). The resultant liposomes entrapped approximately 23.30% of the drug. Using five different bioadhesive agents, inclusion of any of these agents (0.2% w/v) caused a decrease in drug entrapment except for carboxymethyl chitosan which had no effect on the drug entrapment (25.97%). Investigation of aerosolized liposome dispersion using a range of nasal spray devices demonstrated integrity of liposomes were not changed (i.e particle size, Span, and drug entrapment efficiency were unaffected) and RH-loaded liposomes were efficiently delivered from the devices. In conclusion, the finding of this study explored mucoadhesive microspheres entrapped the anti-Parkinson drug, RH, and can potentially be applicable for nasal delivery to enhance nose to brain transport using nasal insufflator for improvement of the symptoms of Parkinson disease and Restless legs syndrome. Similar findings using nasal sprays were found for liposomes. In vivo studies are required in the future to determine the amount of the drug that may reach the blood circulation and brain

Microbial life and deposits in paper machine circuits

Väitöskirjani käsittele mikrobien ja erilaisten kemikaalien rooleja saostumien ja biofilmien muodostumisessa paperi- ja kartonkikoneilla. "Saostuma" tässä työssä tarkoittaa kiinteän aineen kertymää konepinnoille tai rajapinnoille konekierroissa, jotka on tarkoitettu massasulppujen, lietteiden, vesien tai ilman kuljetukseen. Saostumasta tulee "biofilmi" silloin kun sen oleellinen rakennekomponentti on mikrobisolut tai niiden tuotteet. Väitöstyöni työhypoteesina oli, että i. tietämys saostumien koostumuksesta, sekä ii. niiden rakenteesta, biologisista, fysikaalis-kemiallisista ja teknisistä ominaisuuksista ohjaavat tutkijaa löytämään ympäristöä säästäviä keinoja estää epätoivottujen saostumien muodostus tai purkaa jo muodostuneita saostumia. Selvittääkseni saostumien koostumista ja rakennetta käytin monia erilaisia analytiikan työkaluja, kuten elektronimikroskopiaa, konfokaali-laser mikroskopiaa (CLSM), energiadispersiivistä röntgenanalyysiä (EDX), pyrolyysi kaasukromatografiaa yhdistettynä massaspektrometriaan (Py-GCMS), joninvaihtokromatografiaa, kaasukromatografiaa ja mikrobiologisia analyysejä. Osallistuin aktiivisesti innovatiivisen, valon takaisinsirontaan perustuvan sensorin kehittämistyöhön, käytettäväksi biofilmin kasvun mittaukseen suoraan koneen vesikierroista ja säiliöistä. Työni osoitti, että monet paperinvalmistuksessa käytetyistä kemikaaleista reagoivat keskenään tuottaen orgaanisia tahmakerroksia konekiertojen teräspinnoille. Löysin myös kerrostumia, jotka valomikroskooppisessa tarkastelussa oli tulkittu mikrobeiksi, mutta jotka elektronimikroskopia paljasti alunasta syntyneiksi, alumiinihydroksidiksi joka saostui pH:ssa 6,8 kiertokuitua käyttävän koneen viiravesistä. Monet paperintekijät käyttävät vieläkin alunaa kiinnitysaineena vaikka prosessiolot ovat muuttuneet happamista neutraaleiksi. Sitä pidetään paperitekijän "aspiriinina", mutta väitöstutkimukseni osoitti sen riskit. Löysin myös orgaanisia saostumia, joiden alkuperä oli aineiden, kuten pihkan, saippuoituminen (kalsium saippuat) niin että muodostui tahmankasvua ylläpitävä alusta monilla paperi- ja kartonkikoneilla. Näin solumuodoiltaan Deinococcus geothermalista muistuttavia bakteereita kasvamassa lujasti teräskoepalojen pintaan kiinnittyneinä pesäkkeinä, kun koepaloja upotettiin paperikoneiden vesikiertoihin. Nämä deinokokkimaiset pesäkkeet voivat toimia jalustana, tarttumisalustana muiden mikrobien massoille, joka selittäisi miksi saostumat yleisesti sisältävät deinokokkeja pienenä, muttei koskaan pääasiallisena rakenneosana. Kun paperikoneiden käyttämien vesien (raakavedet, lämminvesi, biologisesti puhdistettu jätevesi) laatua tutkitaan, mittausmenetelmällä on suuri merkitys. Koepalan upotusmenetelmällä todettu biofilmikasvu ja viljelmenetelmällä mitattu bakteerisaastuneisuus korreloivat toisiinsa huonosti etenkin silloin kun likaantumisessa oli mukana rihmamaiseti kasvavia bakteereja. Huoli ympäristöstä on pakottanut paperi- ja kartonkikoneiden vesikiertojen sulkemiseen. Vesien kierrätys ja prosessivesien uudelleenkäyttö nostavat prosessilämpötilaa ja lisäävät koneella kiertävien kolloidisten ja liuenneiden aineiden määriä. Tutkin kiertovesien pitoisuuksia kolmessa eriasteisesti suljetussa tehtaassa, joiden päästöt olivat 0 m3, 0,5 m3 ja 4 m3 jätevettä tuotetonnia kohden, perustuen puhdistetun jäteveden uudelleen käyttöön. Nollapäästöisellä tehtaalla kiertovesiin kertyi paljon orgaanisesti sidottua hiiltä (> 10 g L-1), etenkin haihtuvina happoina (maito-, etikka-, propioni- ja voi-). Myös sulfaatteja, klorideja, natriumia ja kalsiumia kertyi paljon, > 1 g L-1 kutakin. Pääosa (>40%) kaikista bakteereista oli 16S rRNA geenisekvenssianalyysien tulosten perusteella sukua, joskin etäistä (< 96%) ainoastaan Enterococcus cecorum bakteerille. 4 m3 päästävältä tehtaalta löytyi lisäksi Bacillus thermoamylovorans ja Bacillus coagulans. Tehtaiden saostumat sisälsivät arkkeja suurina pitoisuuksina, ≥ 108 g-1, mutta tunnistukseen riittävää sekvenssisamanlaisuutta löytyi vain yhteen arkkisukuun, Methanothrix. Tutkimustulokset osoittivat että tehtaan vesikiertojen sulkeminen vähensi rajusti mikrobiston monimuotoisuutta, muttei estänyt liuenneen aineen ja kiintoaineen mineralisoitumista.This thesis deals with the roles of microorganisms and different chemicals in the formation of deposits and biofilms at paper and board machines. "Deposit" in this thesis means solid matter that accumulates and immobilizes on machine areas or interfaces meant for unhindered flow of slurries, liquids or air. The deposit is a "biofilm" when microorganisms, or substances produced by them, are its major or otherwise significant building block. The work in this thesis builds on the hypothesis that i.) knowledge on the biotic and abiotic components of the deposit, and ii.) understanding their roles in the build-up, architecture, biological, physico-chemical and technical properties of the deposit will guide the researcher towards preventing or reversing the formation of unwanted deposits in a sustainable way. Multiple analytical tools were used for documenting the buildup of the deposit, including electron microscopy, confocal laser scanning microscopy (CLSM), energy dispersive X-ray (EDX) analysis, pyrolysis gas chromatography - mass spectrometry (Py-GCMS), ion exchange chromatography, gas liquid chromatography and microbiological analyses. I took actively part in developing innovative tools, based on back-scattered light sensoring that can be used for on-line measurement of biofilm in the water loops and containers of paper machines. In the thesis work it was discovered that many of the paper making chemicals interacted forming organic, adhesive layers on steel surfaces in machine circuits. Structures were found, by light microscopy originally judged as microbes, but electron microscopy revealed that they were alum that precipitated as aluminum hydroxide at pH 6.8 in the white water of recycled fiber using machines. Alum is still used as a fixative today among many paper makers, even if the process conditions have changed from acid to neutral pH. It is considered to be the “aspirin” for paper makers; the risk of this was clearly seen in this thesis work. Organic deposits were found, soaps (calcium soaps) of different compounds, like pitch, at the base of the deposit of many paper/board machines. Bacteria, morphologically resembling Deinococcus geothermalis, were demonstrated to grow as colonies firmly attached to the surface of clean stainless steel coupons, immersed in circulation waters at paper machines. Such deinococcal colonies could function as a pedestal, adhesion aid, for later massive attachment of other microorganisms, explaining why deposits frequently contain deinococci as a small, but never as the major building block of paper machine deposits. For assessing the quality of water (raw water, warm water or bio-water) at the paper machines, the measurement method is important. The correlation between cultivation methods and possible contamination of bacteria seen on the coupon surfaces was low, especially when filamentous bacteria were part of the contamination. Environmental concerns have forced paper and board machines to close their circuits. The circulation and reuse of the process waters lead to higher processing temperatures and increase of the colloidal and dissolved material in the circulations. The chemical composition of three different mills was studied, with different final discharges of, 0 m3, 0.5 m3 and 4 m3 waste water per ton product produced, one with reuse of bio-water. The zero discharge mill accumulated high amounts of organic carbon in the circulation waters (> 10 g L-1), including volatile acids (lactic, acetic, propionic and butyric). Contents of sulfate, chloride, sodium and calcium were also high, > 1 g L-1 of each. The major part (40 %) of all identifiable bacterial 16S rRNA gene sequences were closest but yet distantly related (<96 %) to Enterococcus cecorum. In the 4 m3 per ton product discharging mill, additionally Bacillus thermoamylovorans and Bacillus coagulans were found. Slimes and deposits contained high amounts, ≥108 g-1, of archaea, but only one genus, Methanothrix had a sequence match close enough for identification. The results showed that closing the water circuits strongly limited the diversity of the mill microbiota but allowed efficient mineralization of the dissolved and suspended matter