Skin adhesive hydrogels for the topical delivery of active agents

This thesis illustrates the development of tailor-made, partially hydrated skin adhesive hydrogels as a vehicle for the topical delivery of moisturising agents. Maintaining an optimum hydration level of the stratum corneum ensures that the barrier properties of the skin are preserved. An unsaturated ionic monomer 2-acrylamido-2-methylpropanesulfonic acid sodium salt, glycerol, water, a photoinitiator Irgacure 184 and crosslinker Ebacryl II facilitated the production of monophasic sheet skin adhesives using photopolymerisation. The exploration and modification of the hydrogel components coupled with their influence on the adhesive and dynamic mechanical behaviour led to the development of novel monophasic and biphasic hydrogels. Biphasic pregels comprising of a hydrophobic monomer (epoxidised soybean oil acrylate, lauryl acrylate or stearyl acrylate) micellised with a non ionic surfactant Tween 60 allowed a homogeneous distribution throughout a predominantly hydrophilic phase (2-acrylamido-2-methylpropanesulfonic acid sodium salt, 4-acryloylmorpholine, glycerol and water). Further development of biphasic hydrogel technology led to the incorporation of preformed commercial O/W emulsions (Acronal, Flexbond 150, DM137 or Texicryl 13056WB) allowing the hydrophobic component to be added without prior stabilisation. The topical release of moisturising agents 2-pyrrolidone-5-carboxylic acid, lactobionic acid and d-calcium pantothenate results in the deposition onto the skin by an initial burst mechanism. The hydration level of the stratum corneum was measured using a Comeometer CM 825, Skin Reader MY810 or FT-ATR. The use of hydrophilic actives in conjunction with lipophilic agents for example Vitamin E or Jojoba oil provided an occlusive barrier, which reduced the rate of transepidermal water loss. The partition coefficients of the release agents provided invaluable information which enabled the appropriate gel technology to be selected. In summary the synthetic studies led to the understanding and generation of transferable technology. This enabled the synthesis of novel vehicles allowing an array of actives with a range of solubilities to be incorporated.

Ionic and neutral hydrogels for dermal and ophthalmic applications

This thesis is concerned with the use of ionic and neutral hydrogels in dermal and ocular applications with particular reference to controlled release applications. The work consists of three interconnected themes.The first area of study is the use of skin adhesive bioelectrode hydrogels as ground plate electrodes for ophthalmic iontophoresis applications. The work provides a basis of understanding the relative contributions made by ionic monomers (such as sodium s-(acrylamide)-2-methyl propane sulphonate and acrylic acid-bis-(3-sulfopropyl-ester, potassium salt) and neutral monomers (such as acryloymorpholine, N,N-dimethylacrylamide and N-vinyl pyrrolidone) to adhesion, rheology and impedance of bioelectrode gels. The general advantage of neutral monomers, which have been used to successfully replace ionic monomers, is that they enable more effective control of independent anion and cation species (for example potassium chloride and sodium chloride) unlike ionic monomers where polymerisation produces an immobile polyanion thus limiting cation mobility. Secondly, release from a completely neutral hydrogel under the influence of mechanical shaking was studied for the case of crosslinked polyvinyl alcohol (PVA) containing low concentration of linear soluble PVA in a contact lens application. The soluble PVA was observed to be eluting by reptation from the lens matrix due to the mechanical action of the eyelid. This process was studied in an in vitro model, which in this research was used as a basis for developing a lens made with enhanced release polymer. The third area of work is related to the factors that control drug release (in particular non-steroidal anti-inflammatory drugs) from a hydrogel matrix. This links both electrotherapy applications, such as transcutaneous electrical nerve stimulation, in which the passive diffusion from the gel could be used in conjunction with enhanced transmission across the dermal surface with passive diffusion from a contact lens matrix and the development of therapeutic contact lenses.

Reversible addition–fragmentation chain transfer polymerization of 2-chloro-1,3-butadiene

Controlled polymerization of 2-chloro-1,3-butadiene using reversible addition–fragmentation chain transfer (RAFT) polymerization has been demonstrated for the first time. 2-Chloro-1,3-butadiene, more commonly known as chloroprene, has significant industrial relevance as a crosslinked rubber, with uses ranging from adhesives to integral automotive components. However, problems surrounding the inherent toxicity of the lifecycle of the thiourea-vulcanized rubber have led to the need for control over the synthesis of poly(2-chloro-1,3-butadiene). To this end, four chain transfer agents in two different solvents have been trialed and the kinetics are discussed. 2-Cyano-2-propylbenzodithioate (CPD) is shown to polymerize 2-chloro-1,3-butadiene in THF, using AIBN as an initiator, with complete control over the target molecular weight, producing polymers with low polydispersities (Mw/Mn < 1.25 in all cases).

Clinical performance of daily disposable soft contact lenses using sustained release technology

Purpose: Polyvinyl alcohol (PVA) is a successful tear film stabiliser and is widely used in comfort drops and some soft contact lens materials. A PVA-containing lens, nelfilcon A has been modified to include additional (non-functional) PVA in order to provide improved comfort. This study aims to examine the clinical performance of this nelfilcon A lens with AquaRelease™ (AquaRelease). Methods: Two contralateral, investigator masked, open label, subjective and objective evaluations were conducted. The first examined the effect of adding increased molecular weight PVA to nelfilcon A (n = 5), and the second compared this AquaRelease lens to ocufilcon B (n = 34). The principal measures were non-invasive break-up time (NIBUT) and subjective comfort, which were assessed at the beginning and end of a week of daily wear, and three times throughout 1 day at 8, 12 and 16 h. Results: All subjects successfully completed the daily wearing schedule of 16 h. On initial insertion, subjective comfort and NIBUT improved for AquaRelease than original nelfilcon A lenses (p < 0.05). Initial comfort was better for AquaRelease compared to ocufilcon B lenses (p = 0.01); however, NIBUT was not statistically different (11.7 ± 15.6 s versus 8.4 ± 6.8 s; p = 0.26). Subjective comfort decreased with time (p < 0.001), but there was no significant difference between AquaRelease and ocufilcon B lenses (p = 0.16). NIBUT was not significantly affected by time (p = 0.56) or between lenses (p = 0.33). At the end of a weeks' wear, subjective initial, end-of-day, overall comfort and vision were rated significantly better with AquaRelease than ocufilcon B (p < 0.01). Conclusions: Release of additional non-functionalised PVA from the nelfilcon A lenses appears to enhance comfortable contact lens wear. © 2006 British Contact Lens Association.

Controlled RAFT polymerization and zinc binding performance of catechol-inspired homopolymers

Incorporation of catechols into polymers has long been of interest due to their ability to chelate heavy metals and their use in the design of adhesives, metal-polymer nanocomposites, antifouling coatings, and so on. This paper reports, for the first time, the reversible addition-fragmentation chain transfer (RAFT) polymerization of a protected catechol-inspired monomer, 3,4-dimethoxystyrene (DMS), using commercially available trithiocarbonate, 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT), as a chain transfer agent. Our identified RAFT system produces well-defined polymers across a range of molecular weights (5-50 kg/mol) with low molar mass dispersities (Mw/Mn < 1.3). Subsequent facile demethylation of poly(3,4-dimethoxystyrene) (PDMS) yields poly(3,4-dihydroxystyrene) (PDHS), a catechol-bearing polymer, in quantitative yields. Semiquantitative zinc binding capacity analysis of both polymers using SEM/EDXA has demonstrated that both PDMS and PDHS have considerable surface binding (65% and 87%, respectively), although the films deposited from PDMS are of a better quality and processability due to solubility and lower processing temperatures. © 2014 American Chemical Society.

Physical and biological properties of a novel siloxane adhesive for soft tissue applications

The aim of this study was to investigate the adhesive properties of an in-house amino-propyltrimethoxysilane-methylenebisacrylamide (APTMS-MBA) siloxane system and compare them with a commercially available adhesive, n-butyl cyanoacrylate (nBCA). The ability of the material to perform as a soft tissue adhesive was established by measuring the physical (bond strength, curing time) and biological (cytotoxicity) properties of the adhesives on cartilage. Complementary physical techniques, X-ray photoelectron spectroscopy, Raman and infrared imaging, enabled the mode of action of the adhesive to the cartilage surface to be determined. Adhesion strength to cartilage was measured using a simple butt joint test after storage in phosphate-buffered saline solution at 37°C for periods up to 1 month. The adhesives were also characterised using two in vitro biological techniques. A live/dead stain assay enabled a measure of the viability of chondrocytes attached to the two adhesives to be made. A water-soluble tetrazolium assay was carried out using two different cell types, human dermal fibroblasts and ovine meniscal chondrocytes, in order to measure material cytotoxicity as a function of both supernatant concentration and time. IR imaging of the surface of cartilage treated with APTMS-MBA siloxane adhesive indicated that the adhesive penetrated the tissue surface marginally compared to nBCA which showed a greater depth of penetration. The curing time and adhesion strength values for APTMS-MBA siloxane and nBCA adhesives were measured to be 60 s/0.23 MPa and 38 min/0.62 MPa, respectively. These materials were found to be significantly stronger than either commercially available fibrin (0.02 MPa) or gelatin resorcinol formaldehyde (GRF) adhesives (0.1 MPa) (P <0.01). Cell culture experiments revealed that APTMS-MBA siloxane adhesive induced 2% cell death compared to 95% for the nBCA adhesive, which extended to a depth of approximately 100-150 μm into the cartilage surface. The WST-1 assay demonstrated that APTMS-MBA siloxane was significantly less cytotoxic than nBCA adhesive as an undiluted conditioned supernatant (P <0.001). These results suggest that the APTMS-MBA siloxane may be a useful adhesive for medical applications. © VSP 2005.

Shear induced toughening in bonded joints:experiments and analysis

Bonded joint specimens were fabricated from composite adherends and either an epoxy or a urethane adhesive. In mixed-mode fracture experiments, the epoxy bonded specimens generally failed by subinterfacial fracture in the composite, while specimens bonded with urethane failed very close to the adhesive/substrate interface. For the epoxy bonded specimens, fracture toughness did not change significantly with mode-mix, but for urethane bonded joints, fracture toughness increased with increasing shear load. Finite element analysis, which modeled specimens bonded with the two adhesives, showed similar trends. The different toughening behaviors for the two bonded joints can be attributed to dissipation of energy through inelastic deformation, which was insignificant in the epoxy-bonded joints but substantial when the urethane was used as the bonding agent.

Biomaterial interactions with compromised tissue surfaces

This thesis is concerned with the nature of biomaterial interactions with compromised host tissue sites. Both ocular and dermal tissues can be wounded, following injury, disease or surgery, and consequently require the use of a biomaterial. Clear analogies exist between the cornea/tear film/contact lens and the dermal wound bed/wound fluid/skin adhesive wound dressing. The work described in this thesis builds upon established biochemistry to examine specific aspects of the interaction of biomaterials with compromised ocular and dermal tissue sites, with a particular focus on the role of vitronectin. Vitronectin is a prominent cell adhesion glycoprotein present in both tear fluid and wound fluid, and has a role in the regulation and upregulation of plasmin. The interaction of contact lenses with the cornea was assessed by a novel on-lens cell-based vitronectin assay technique. Vitronectin mapping showed that vitronectin-mediated cell adhesion to contact lens surfaces was due to the contact lens-corneal mechanical interaction rather than deposition out of the tear film. This deposition is associated predominantly with the peripheral region of the posterior contact lens surface. The locus of vitronectin deposition on the contact lens surface, which is affected by material modulus, is potentially an important factor in the generation of plasmin in the posterior tear film. Use of the vitronectin mapping technique on ex vivo bandage contact lenses revealed greater vitronectin-mediated cell adhesion to the contact lens surfaces in comparison to lenses worn in the healthy eye. The results suggest that vitronectin is more readily deposited from the impaired corneal tissue bed than the intact healthy tissue bed. Significantly, subjects with a deficient tear film were found to deposit high vitronectin-mediated cell adhesion levels to the BCL surface, thus highlighting the influence of the contact lens-tissue interaction upon deposition. Biomimetic principles imply that adhesive materials for wound applications, including hydrogels and hydrocolloids, should closely match the surface energy parameters of skin. The surface properties of hydrocolloid adhesives were found to be easily modified by contact with siliconised plastic release liners. In contrast, paper release liners did not significantly affect the adhesive surface properties. In order to characterise such materials in the actual wound environment, which is an extremely challenging task, preliminary considerations for the design of an artificial wound fluid model from an animal serum base were addressed.

Eco-car : a perfect vehicle for technical design teaching?

Design methods and tools are generally best learned and developed experientially [1]. Finding appropriate vehicles for delivering these to students is becoming increasingly challenging, especially when considering only those that will enthuse, intrigue and inspire. This paper traces the development of different eco-car design and build projects which competed in the Shell Eco-Marathon. The cars provided opportunities for experiential learning through a formal learning cycle of CDIO (Conceive, Design, Implement, Operate) or the more traditional understand, explore, create, validate, with both teams developing a functional finished prototype. Lessons learned were applied through the design of a third and fourth eco-car using experimental techniques with bio-composites, combining the knowledge of fibre reinforced composite materials and adhesives with the plywood construction techniques of the two teams. The paper discusses the importance of applying materials and techniques to a real world problem. It will also explore how eco-car and comparing traditional materials and construction techniques with high tech composite materials is an ideal teaching, learning and assessment vehicle for technical design techniques.

Desenvolvimento de bionanocompósitos: nano e microcristais de celulose com poli (álcool vinílico) e poli (ácido lático)

This work has the main objective to obtain nano and microcrystals of cellulose, extracted from the pineapple leaf fibres (PALF), as reinforcement for the manufacture of biocomposite films with polymeric matrices of Poly(vinyl alcohol) (PVA) and Poly(lactic acid) (PLA). The polymer matrices and the nano and microcrystals of cellulose were characterised by means of TGA, FTIR and DSC. The analysis was performed on the pineapple leaves to identify the macro and micronutrients. The fibers of the leaves of the pineapple were extracted in a desfibradeira mechanical. The PALF extracted were washed to remove washable impurities and subsequently treated with sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) in the removal of impurities, such as fat, grease, pectates, pectin and lignin. The processed PALF fibers were hydrolysed in sulfuric acid (H2SO4) at a concentration of 13.5 %, to obtain nano and microcrystals of cellulose. In the manufacture of biocomposite films, concentrations of cellulose, 0 %, 1 %, 3 %, 6 %, 9% and 12% were used as reinforcement to the matrices of PVA and PLA. The PVA was dissolved in distilled water at 80 ± 5 oC and the PLA was dissolved in dichloromethane at room temperature. The manufacture of biocompósitos in the form of films was carried out by "casting". Tests were carried out to study the water absorption by the films and mechanical test of resistance to traction according to ASTM D638-10 with a velocity of 50 mm/min.. Chi-square statistical test was used to check for the existence of significant differences in the level of 0.05: the lengths of the PALF, lengths of the nano and microcrystals of cellulose and the procedures used for the filtration using filter syringe of 0.2 μm or filtration and centrifugation. The hydrophilicity of biocompósitos was analysed by measuring the contact angle and the thickness of biocompósitos were compared as well as the results of tests of traction. Statistical T test - Student was also applied with the significance level (0.05). In biodegradation, Sturm test of standard D5209 was used. Nano and microcrystals of cellulose with lengths ranging from 7.33 nm to 186.17 nm were found. The PVA films showed average thicknesses of 0.153 μm and PLA 0.210 μm. There is a strong linear correlation directly proportional between the traction of the films of PVA and the concentration of cellulose in the films (composite) (0,7336), while the thickness of the film was correlated in 0.1404. Nano and microcrystals of cellulose and thickness together, correlated to 0.8740. While the correlation between the cellulose content and tensile strength was weak and inversely proportional (- 0,0057) and thickness in -0.2602, totaling -0,2659 in PLA films. This can be attributed to the nano and microcrystals of cellulose not fully adsorbed to the PLA matrix. In the comparison of the results of the traction of the two polymer matrices, the nano and microcrystals have helped in reducing the traction of the films (composite) of PLA. There was still the degradation of the film of PVA, within a period of 20 days, which was not seen in the PLA film, on the other hand, the observations made in the literature, the average time to start the degradation is above 60 days. What can be said that the films are biodegradable composites, with hydrophilicity and the nano and microcrystals of cellulose, contribute positively in the improvement of the results of polymer matrices used.

Desenvolvimento de pastas cimentantes contendo nanossílica como material estendedor para aplicação em fases iniciais, de poços petrolíferos, submetidas à baixa temperatura (5°c ± 3ºc)

The improved performance of hydraulic binders, the base of Portland cement, consists in the careful selection and application of materials that promote greater durability and reduced maintenance costs There is a wide variety of chemical additives used in Portland cement slurries for cementing oil wells. These are designed to work in temperatures below 0 ° C (frozen areas of land) to 300 ° C (thermal recovery wells and geothermal); pressure ranges near ambient pressure (in shallow wells) to greater than 200 MPa (in deep wells). Thus, additives make possible the adaptation of the cement slurries for application under various conditions. Among the materials used in Portland cement slurry, for oil wells, the materials with nanometer scale have been applied with good results. The nanossílica, formed by a dispersion of SiO2 particles, in the nanometer scale, when used in cement systems improves the plastic characteristics and mechanical properties of the hardened material. This dispersion is used commercially as filler material, modifier of rheological properties and / or in recovery processes construction. It is also used in many product formulations such as paints, plastics, synthetic rubbers, adhesives, sealants and insulating materials Based on the above, this study aims to evaluate the performance of nanossílica as extender additive and improver of the performance of cement slurries subjected to low temperatures (5 ° C ± 3 ° C) for application to early stages of marine oil wells. Cement slurries were formulated, with densities 11.0;12.0 and 13.0 ppg, and concentrations of 0; 0.5, 1.0 and 1.5%. The cement slurries were subjected to cold temperatures (5 ° C ± 3 ° C), and its evaluation performed by tests rheological stability, free water and compressive strength in accordance with the procedures set by API SPEC 10A. Thermal characterization tests (TG / DTA) and crystallographic (XRD) were also performed. The use of nanossílica promoted reduction of 30% of the volume of free water and increased compression resistance value of 54.2% with respect to the default cement slurry. Therefore, nanossílica presented as a promising material for use in cement slurries used in the early stages of low-temperature oil wells

Obtenção de triacetato de celulose a partir do bagaço de cana-deaçúcar para revestimento de micropartículas de goma gelana e avaliação do seu perfil de liberação in vitro e da mucoadesão ex vivo

Oral route of administration is considered to be the most comfortable, safe and greater adaptation for patients. But, oral route presents some disadvantages such as drugs bioavailability and side effects on the stomach. Some technologies are studied to soften and/or resolve these problems, such as coating with polymeric films, which are able to protect the pharmaceutical form of the acid stomachic environment and to act in the drug release, and mucoadhesive systems, which allow the pharmaceutical form remains a greater time interval in the intestine, increasing the effectiveness of the drug. Cellulose triacetate (CTA) films were produced from cellulose extracted from sugar cane bagasse. The films were prepared with different morphologies (with and without water, acting as non-solvent) and concentrations (3, 6.5 and 10%) of CTA and characterized using scanning electron microscopy (SEM), water vapor permeability (WVP), puncture resistance (PR), enzymatic digestion (DE), and mucoadhesive force evaluation (MF). Microscopy showed the formation of symmetric and asymmetric morphologies. WVP data showed that more concentrated films have higher values for WVP; moreover, asymmetric films had higher values than symmetric films. PR measurements showed that symmetric membranes are more resistant than asymmetric ones. More concentrated films were also more puncture resistant, except for symmetric membranes with CTA concentrations of 6.5 and 10% that did not show significant differences. All of the films presented large mucoadhesive capacities independent of their morphology and CTA concentration. From the results of WVP and RP, a symmetric filme with 6.5% CTA showed better ability and mechanical resistance, therefore, was selected to serve as coating of gellan gum (GG) particles incorporating ketoprofen (KET), which was confirmed by SEM. The selected film presented low values in measurements of the swelling index (SI) and in a dissolution test (DT). TGA analysis showed that the CTA coating does not influence the thermal stability of the particles and there is no incompatibility evidence between CTA, GG and KET. Coated particles released 100% of the ketoprofen in 24 h, while uncoated particles released the same amount in 4 h. The results of this study highlight the potential of CTA in the development of new controlled oral delivery systems.

Fibrillar Elastomeric Micropatterns Create Tunable Adhesion Even to Rough Surfaces

Acknowledgements V.B., N.K.G., and E.A. contributed with conception and experimental design. V.B. performed the experiments. V.B., R.H., A.G., and R.M.M. carried out analysis and interpretation of data. V.B., R.H., A.G., and E.A. wrote the manuscript. V.B. and R.H. contributed equally to this work. V.B. acknowledges funding by SPP 1420 of the German Science Foundation DFG. E.A., N.K.G., and R.H. acknowledge funding from the European Research Council under the European Union/ERC Advanced Grant “Switch2Stick,” Agreement No. 340929.

A cultura organizacional e a centralidade nas redes sociais: Um estudo exploratório em uma empresa de serviços

O presente artigo apresenta uma pesquisa de campo sobre cultura organizacional e redes sociais que foi realizada junto a uma empresa prestadora de serviços. O objetivo foi verificar se existe a influência da cultura da organização nas características dos grupos sociais, com ênfase na centralidade. A literatura nacional e internacional evidencia que trabalhar com a centralidade significa identificar a posição em que o ator se encontra em relação às trocas e à comunicação na rede; a centralidade em uma rede traz a idéia de poder, isto é, quanto mais central é o indivíduo, mais bem posicionado ele está em relação às trocas e a comunicação. Trata-se de um estudo exploratório de natureza quantitativo; o levantamento feito através de dois questionários elaborados por Nelson(2006 e 2007), pesquisador da Illinois University. O primeiro relativo à cultura organizacional denominado Perfil de Valores Agregados (PVA), que identifica a presença e as prioridades atribuídas dentro de uma organização quanto aos temas: Trabalho “tarefa”, Relações “sociais”, Controle “poder“ e Cognição “Pensamento”. O segundo relativo às redes formadas cujo instrumento constituiu-se da apresentação de uma lista com todos os participantes da pesquisa e foi solicitado a cada membro que informasse sobre a natureza dos contatos adjacentes a cada nome. Os campos nome e cargo já foram entregues pré-preenchidos pelos pesquisadores, os campos aprovações e número de e-mails recebidos e enviados foram preenchidos por meio de estimativa do respondente e o campo dependência foi respondido respeitando-se uma escala de 1 a 6, onde 1 representava pouca e 6 muita dependência da outra pessoa. Utilizou-se uma amostra de 58 respondentes, todos funcionários próprios da empresa prestadora de serviços. Os dados foram tratados pela técnica estatística não-paramétrica Mann Whitney para os valores da cultura e para os dados das redes Sociais os índices foram apurados por meio do software Ucinet 6.0 de Borgatti, Everett, e Freeman (2002). Os resultados mostraram que os elementos centrais, ou seja, aqueles que têm o maior número de contatos na rede têm um maior alinhamento dos seus valores com os padrões da cultura organizacional e se concluiu que estes podem influenciar e participar na disseminação dos valores presentes na cultura organizacional. O que se pode perceber ao se analisar relação de nomes e funções dos colaboradores é que os quatro atores mais centrais da rede (centralidade) exercem funções gerenciais ou exercem algum tipo de liderança dentro da organização pesquisada; uma delas é Sub-gerente Operacional , duas outras são Supervisoras e a ultima é Assistente Operacional e trabalha diretamente com a Gerente Operacional. Os benefícios e a minimização de custos nas interações sociais caso a empresa utilize estes elementos centrais em programas de coaching ou mentoring, ou em outras ações de mudança, pode favorecer a retirada dos colaboradores da sua zona de conforto e ajudar a disseminar mais rapidamente a Missão, Visão e Valores Organizacionais.