Asthma is a significant lung disease involving chronic inflammation and remodeling of the airways, resulting in reduced quality of life for those who suffer from the condition. Current therapeutic guidelines suggest the use of inhaled corticosteroids for long-term anti-inflammatory relief to manage moderate to severe chronic asthma; however, inhaled corticosteroids fail to provide prophylactic or reversal treatment of damaged airways incurred by chronic asthma as well as exhibiting adverse side effects (skeletal complications, diabetes, and weight gain).Therefore, there is a need for a new type of drug therapy to address these gaps in the treatment of chronic asthma. There is growing interest aimed towards the inhibition of the Janus Kinase and Signal Transducer and Activator of Transcription (JAK-STAT) pathway for the treatment of asthma. Despite the promising opportunity to investigate this new pathway towards this clinical application, no published work is available using an established and characterized JAK 1/3 inhibitor for the treatment of chronic asthma delivered via inhalation. This work investigated tofacitinib citrate, a selective JAK 3 inhibitor, and its potential to be delivered locally to the lungs for the treatment of chronic asthma. Several preformulation studies were conducted to determine the basic physical and chemical properties of the compound and its free base, tofacitinib, for proper inhalational formulation development. The drug was delivered to BALB/c mice challenged with house dust mite (HDM) allergen via nebulization utilizing a nose-only chamber. After a three week dosing schedule, mice treated with tofacitinib citrate exhibited an increase in monocyte cell numbers with a simultaneous decrease in eosinophil cell count, gathered from BAL fluid. Further, the experimental groups treated with tofacitinib citrate had a decrease in total protein concentrations in comparison to the experimental groups that were only challenged with HDM or were both exposed to HDM and vehicle. These findings demonstrated that the proper formulation was developed for nebulized delivery of tofacitinib citrate, and that the compound was capable of reducing total protein concentrations and eosinophil cell recruitment, both recognized as biomarkers for an asthmatic response. Although significant work is still needed to be done, these data hold promise for the potential of a locally delivered JAK 3 inhibitor as a treatment for chronic asthma. Further, the solubility of tofacitinib citrate and five other pharmaceutical salts were determined in HFA 134a, HFA 227, and DFP with varying cosolvent content (0-20% v/v ethanol). The experimental solubilities of the free acid and base compounds were larger than the solubilities of their respective salts in all three systems for tofacitinib, albuterol, and salicylic acid. Warfarin, phenytoin, and ciprofloxacin had similar solubilities with their respective salt forms. Solubilities also increased with increasing cosolvent concentration for all compounds investigated. The model propellant, DFP, provided a slightly stronger correlation of solubility values with HFA 134a in comparison to HFA 227. The observed solubility values were also compared to calculated values obtained from the ideal solubility model, where it was determined that the observed solubility was indeed also dependent on its surrounding solvent interactions and not solely on its ideal solubility (melting point). While some physical changes were observed for the pharmaceutical salts in HFA 134a and 227, more quantitative studies are needed for a larger database of compounds to better understand the factors that contribute to the solubility of pharmaceutical salts (and their correlation to DFP), in HFA-based systems. This information could potentially contribute to a predictive model, saving time and money during the process of pMDI formulation development.

he objective of this research was to investigate the feasibility of using the pyrolysis bio-oil as part of a binder system for wood-based composites. Liquid products obtained from pyrolysis process of pine wood were mixed with reactants, such as isocyanate. The adhesive binder system was blended with flakes to fabricate flakeboard. The effect of the resin content and the mix ratio of the adhesive on the physical and mechanical properties of the flakeboard were examined. Dynamic mechanical analysis (DMA) was also employed to investigate the thermal properties of the adhesives. The results indicated that a bio-oil content of 25% showed comparable properties to those produced by pure pMDI adhesive. A good correlation between the DMA results and the mechanical properties of the flakeboard was also obtained. The increase of bio-oil content in the adhesive system improved the curing speed but reduced the adhesive stiffness.

Introduction: Although patients with an acute increase in airflow resistance may require aerosol therapy and noninvasive positive pressure ventilation (NIPPV), the efficiency of different aerosol devices and masks during NIPPV is not well understood. The purpose of this study was to determine the efficiency of a jet nebulizer (JN), a vibrating mesh nebulizer (VMN) and a pressurized metered-dose inhaler (pMDI) and three different masks during NIPPV. Method: An in vitro lung model consisted of the upper airway of an adult teaching manikin with a collecting filter at the level of the bronchi attached to a passive test lung. NIPPV was administered via full face mask for the first experiment (AF531 oro-nasal) with an IPAP/EPAP of 20/5 cm H2O and a respiratory rate of 15 Breath per minute (BPM). Aerosol generators were placed between the leak in the circuit and the mask. Albuterol sulfate (2.5 mg/ 3 ml) was nebulized with the JN (Micromist) and the VMN (Aeroneb Solo). Four puffs (108 µg/puff) were administered with the pMDI (ProAir HFA) with a spacer (Aerovent) that first was placed in the recommended normal position (pMDI-N) with aerosol plume directed towards patient, and then in the reversed position (pMDI-R), with aerosol directed away from patient (n=3). In the second experiment, three masks were used 1) the Performax mask, 2) the AF531 oro-nasal mask, and 3) the Performa track mask. Performa track mask was tested with only Aeroneb solo while other masks were tested with both Aeroneb solo and NIVO VMNs. In both experiments, filters were eluted with 0.1 HCl and analyzed by a spectrophotometer at 276 nm. Residual volumes were determined gravimetrically. Result: Descriptive statistics, one-way analysis of variance (ANOVA), and independent t tests were used. Statistical significance was set at p<0.05. During NIPPV, inhaled mass (IM) and inhaled mass percent (IM %) varied significantly (p=0.042 and p=0.028, respectively). Aerosol delivery with the JN was the lowest during NIPPV. The VMN has a significantly lower residual volume than the JN (p=0.0001). No statistical difference in efficiency was found between the two pMDI orientations (p=0.253). In the second experiment, oro nasal mask with Aeroneb Solo VMN results in the highest IM which was significant when compared with all other masks(p=0.0001). No statistical difference can be found between other masks. Conclusion: The JN was less efficient than the VMN and the pMDI in either orientation. The type of aerosol device used during NIPPV influenced aerosol delivery in this simulated adult lung model. Oro nasal mask with Aeroneb Solo VMN provided the highest IM.

Background: HFNC system is a novel device used with aerosol therapy and seems to be rapidly accepted. Although there are some studies conducted on HFNC and vibrating mesh nebulizer, the effect of HFNC on aerosol delivery using jet nebulizer or pressurized metered-dose inhaler (pMDI) has not been reported. In an effort to examine the effect of HFNC on aerosol deposition, this study was conducted to quantify aerosol drug delivery with or without a HFNC using either pMDI or jet nebulizer. Methodology: The SAINT model, attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc., Englewood, CO, USA) for aerosol collection, was connected to a pediatric breathing simulator (Harvard Apparatus, Model 613, South Natick, MA, USA). To keep the filter and the SAINT model in upright position to collect aerosolized drug, an elbow adapter was connected between the absolute filter and the breathing simulator. An infant HFNC (Optiflow, Fisher & Paykel Healthcare LTD., Auckland, New Zealand) ran at 3 l/min O2 was attached to the nares of the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Aerosol drug was administered using: 1) Misty-neb jet nebulizer (Allegiance Healthcare, McGaw Park, Illinois, USA) powered by air at 8 l/min using pediatric aerosol facemask (B&F Medical, Allied Healthcare Products, Saint Louis, MO, USA) to deliver albuterol sulfate (2.5 mg/3 mL NS), and 2) Four actuations of Ventolin HFA pMDI (90 μg/puff) (GlaxoSmithKline, Research Triangle Park, NC, USA) combined with VHC (AeroChamber plus with Flow-Vu, Monaghan Medical, Plattsburgh, NY, USA). Aerosol was administered to the model with and without the HFNC and another without (n=3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. Independent t tests were performed for data analysis. Statistical significance was determined with a p value of <0.05. Results: The mean inhaled mass percent was greatest for pMDI with (p = 0.0001) or without HFNC (p = 0.003). Removing HFNC from the nares before aerosol treatment trended to increase drug delivery with the jet nebulizer (p = 0.024), and increased drug delivery by 6 fold with pMDI (p = 0.003). Conclusions: Aerosol drug may be administered in pediatrics receiving HFNC therapy using either jet nebulizer or pMDI. However, using pMDI, either with or without HFNC, is the best option. When delivering medical aerosol by mask, whether by jet nebulizer or pMDI, removing HFNC led to an increase in inhaled mass percent. However, the benefit of increased aerosol delivery must be weighed against the risk of lung derecruitment when nasal prongs are removed.

Background: Aerosol therapy has been established as an efficient form of drug delivery to pediatric and adult patients with respiratory diseases; however, aerosol delivery to the pediatric population is quite challenging. While some studies compare jet nebulizer (JN), vibrating mesh nebulizer (VMN), or JN and pMDI, there is no study comparing these three devices in pediatric and young children. The aim of this study quantifies aerosol deposition using JN, VMN, and pMDI/VHC in a simulated pediatric with active and passive breathing patterns. Methods: Each aerosol generator was placed between manual resuscitator bag (Ambu SPUR II Disposable Resuscitator, Ambu Inc, Glen Burnie, MD) and infant facemask (Mercury Medical, Cleanwater, FL), which was held tightly against the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Active and passive breathing patterns were used in this study with aerosol device; active breathing pattern was created using a ventilator (Esprit Ventilator, Respironics/Philips Healthcare, Murrysville, PA) connected to a dual chamber test lung (Michigan Instruments, Grand Rapids, MI), which was attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc, Englewood, CO), to collect aerosolized drug, connected to the SAINT model. Pediatric resuscitator bag was run at 10 L/min of oxygen and attached to aerosol generator with facemask. In passive breathing pattern, SAINT model was attached to test lung and ventilated using the resuscitator bag with the same breathing parameters. Each aerosol device was tested three times (n=3) with each breathing patterns. Drug was eluted from the filter and analyzed using spectrophotometry. The amount of drug deposited on the filter was quantified and expressed as a percentage of the total drug dose. To measure the differences in the inhaled drug mass between JN, VMN, and pMDI/VHC in active or passive breathing, one-way analysis of variance (one-way ANOVA) was performed. To quantify the difference in aerosol depositions between the two breathing patterns, independent t-test was performed. A p < 0.05 was considered to be statistically significant. Results: Although the amount of aerosol deposition with the JN was the same in passive and active breathing without any significant difference, the VMN was more efficient in active breathing than the JN (p = 0.157 and p = 0.729, respectively). pMDI/VHC had the greatest deposition in the simulated spontaneous breathing (p=0.013) Conclusion: Aerosol treatment may be administered to young children using JN, VMN, or pMDI/VHC combined with resuscitator bag. Using pMDI/VHC with resuscitator bag is the best choice to deliver albuterol in spontaneously breathing children. Further studies are needed to determine the effectiveness of these aerosol generators with different type of resuscitator bag and different breathing parameters.

Within pressurised Metered Dose Inhalers (pMDIs) the contact between the valve components and elastomeric seals is of major significance, representing the main contributory factor to the overall system frictional characteristics. Therefore, the seal performance is extremely important and must be optimised to meet the contradictory requirements of preventing leakage and allowing smooth actuation. The environmentally driven trend to HFA formulations as opposed to CFC based ones has deteriorated this problem due to poor lubrication conditions and it has, consequently, increased the frictional losses during the pMDI actuation (hysteresis cycle). Research has been conducted into the key areas of the inhaler mechanism. As such, the contact pressure distribution and resulting reactions have been investigated, with emphasis on the correct treatment of the elastomer (seal) characteristics. The modelling of the device has been conducted within the environment of the multibody dynamics commercial software ADAMS, where a virtual prototype has been built using solid CAD geometries of the valve components. An equation was extrapolated to describe the relation between the characteristics of the ultra thin film contact conditions (sliding velocity, surface geometry, film thickness and reaction force) encountered within the inhaler valve and integrated into the virtual prototype allowing the calculation of friction within the conjuncture (due to viscous shear and adhesion). The latter allowed the analysis and optimisation of key device parameters, such as seal geometry, lubricant properties etc. It has been concluded that the dominant mechanism of friction is adhesion, while boundary lubrication is the prevailing lubrication regime due to the poor surface roughness to film thickness ratio. The multibody dynamics model represents a novel multi physics approach to study the behaviour of pMDIs, including rigid body inertial dynamics, general elasticity, surface interactions (such as adhesion), hydrodynamics and intermolecular surface interactions (such as Van der Waals forces). Good agreement has been obtained against experimental results at component and device level.

Inhaled corticosteroids (ICS) are used to address inflammatory illnesses including asthma and COPD, with delivery commonly achieved using pressurised metered dose inhalers (pMDI). Hydrofluoroalkanes (HFAs) have been introduced as an alternative propellant to chlorofluorocarbons (CFCs) to reduce their environmental impact. However, the thermodynamic properties of HFAs are poorly understood and are different to those of CFCs. It is essential, therefore, to characterise the drugs and excipients used in HFA inhalers in order to obtain a comprehensive understanding of the device performance and the therapeutic efficacy. This work has developed different analytical methods to study the complexation between ICS and CD which are added to enhance the solubility of inhaled drugs in pMDI propellant systems providing rational control of suspension vs. solution formulations and hence their dose uniformity and stability. The Nuclear Magnetic Resonance (NMR) method developed has shown weaker complexation between budesonide and the derivatised CDs DIMEB and TRIMEB in organic solvents compared to D2O with the strength of the complex formed being ranked as D2O > MeOD > CDCl3 > CD3CN. The derivatisation of the CD also shows a marked difference in complexation with budesonide with the strength of the association being ranked as DIMEB > βCD > TRIMEB. Studies of various ICS compounds with TRIMEB in the fluorinated propellant HPFP showed the association to be greatest in budesonide, followed by beclomethasone dipropionate, momestasone furoate and fluticasone propionate. Surface-enhanced Raman scattering (SERS) has been used for the detection of corticosteroids in water using thiol functionalised βCD as a complementary study to NMR. This has been utilised to evaluate the host-guest complexes formed and provides further insight into the complexation of the compounds by their inclusion into the CD cavity. The structural data obtained using the NMR and SERS approaches developed have provided a fundamental insight into the physical chemistry of these interactions at a molecular level.

Materiais altamente especializados (polifuncionais) continuam a ser candidatos chave para avanços na área tecnológica e biológica. Buscando aplicação em campos diversos, foram sintetizadas estruturas dendríticas (dendrímeros e polímeros hiperramificados) do tipo poliéster. Esses materiais foram utilizados para dois fins distintos, a aplicação em sistemas de Drug Delivery e em sistemas catalíticos. Em relação aos sistemas de Drug Delivery, foram estudados dois aspectos principais: (i) Impregnação de fármacos na matriz dendrimérica utilizando scCO2 como solvente - foi estudado o comportamento dos materiais frente ao solvente neotério em termos de estrutura (arquitetura da macromolécula), grupos modificadores (acetonida, hidroxila, acetila e cadeia lineares de polilactato) e densidade do solvente. Os materiais que apresentaram características adequadas foram utilizados no estudo da impregnação de fármacos modelo (Ibuprofeno e Fluconazol) na matriz dendrimérica, utilizando-se scCO2 como solvente. Ambos os fármacos foram eficientemente aprisionados no interior da matriz e apresentaram interações com sua estrutra (analisadas por espectroscopia Raman e 1H RMN). (ii) Estudo do potencial para uso como nanocarreadores em Drug Delivery destinados as vias aéreas - Estudou-se o emprego dos dendrímeros do tipo poliéster de diferentes gerações (G3 e G4) modificados com um marcador fluorescente (FITC), conjugados ou não a poli(etilenoglicol) (PEG), como potenciais nanocarreadores para sistemas de Drug Delivery destinados as vias aéreas. Foram realizados testes in vitro para avaliar o transporte e a internalização desses materiais em um modelo de epitélio pulmonar (monocamada de células Calu-3). O transporte e internalização se mostraram dependentes do tamanho da espécie, sendo que dendrímeros conjugados com PEG apresentaram baixa internalização e mais eficiente transporte através da monocamada, situação oposta à ocorrida com os dendrímeros não conjugados. Estudou-se a degradabilidade desses materiais em condições de pH de relevância biológica, assim como a citotoxicidade dos dendrímeros íntegros e de seus fragmentos frente às células Calu-3, sendo que todas as espécies demonstraram baixa toxicicidade na faixa de concentração estudada. O dendrímero modificado com PEG foi utilizado em uma formulação do tipo \"pressurized metered-dose inhaler\" (pMDI). A performance do aerossol obtido com o pMDI foi avaliada, in vitro, através de um impactador de cascata de Andersen (Andersen Cascade Impactor, ACI), mostrando excelentes resultados, com ao redor de 90% da formulação atingindo regiões profundas do pulmão (eg. alvéolos). Em relação à aplicação em sistemas catalíticos, poliésteres hiperramificados, similares aos dendrímeros empregados nos demais estudos, foram modificados de modo a se obter grupos -NH2 terminais e utilizados para magnificação de performance de catalisadores baseados em ródio. Os poliésteres hiperramificados modificados foram imobilizados em nanopartículas ferromagnéticas, do tipo Fe3O4@SiO2, a fim de se obter uma elevada densidade de grupos aminos terminais, os quais foram posteriormente modificados e serviram de ancoragem para um catalisador de Rh. Foi avaliado o incremento do conteúdo de metal na nanopartícula (de 0,2% para 1,0% m/m), assim como seu efeito catalítico em reações de hidroformilação. / Highly specific materials (polyfunctional) continue to be key candidates to address the challenges of technological and biological fields. Aiming to reach different applications, polyester dendritic structures (dendrimers and hyperbranched polymers) were synthesized. These materials were used in two different ways, application in Drug Delivery systems and in catalytic systems. Regarding the usage in the Drug Delivery systems, two major aspects were studied: (i) Impregnation of drugs in the dendrimeric matrix using scCO2 as solvent - It was studied the behavior of these materials in the neoteric solvent in terms of structure (architecture of the macromolecule), modifying groups (acetonide, hydroxyl, acetyl and linear polylactide chains) and density of the solvent. The materials that showed appropriate characteristics were used for the impregnation of model drugs (Ibuprofen and Fluconazole) in the dendrimeric matrix, using scCO2 as solvent. The two drugs were efficiently trapped in the matrix, and showed interactions with its structure (analyzed by Raman Spectroscopy and 1H NMR) (ii) Study of potential usage as nanocarriers in Drug Delivery systems for the airways - It was studied the application of polyester dendrimers of different generations (G3 and G4), labeled with FITC and conjugated or not with polyethylene glycol (PEG) as potentials nanocarriers for Drug Delivery systems for the airways. In vitro tests were performed to analyze the transport and internalization of these materials in a model of lung epithelia (Calu-3 monolayer). Transport and internalization showed to be size dependent, where the PEGylated dendrimers showed low internalization and more efficient transport through the monolayer, with the opposite situation for the non-conjugated dendrimers. The degradation of the materials was studied in biological relevant values of pH, as well the cytotoxicity on Calu-3 of the dendrimers and their building-blocks. All materials showed very low cytotoxicity in the range of concentrations used. The G4 PEGylated dendrimer was used to prepare a pMDI (pressurized metered-dose inhaler) formulation. The performance of the resulting aerosol was evaluated, in vitro, using an eight stage Andersen Cascade Impactor (ACI). The results showed excellent deep lung deposition, where almost 90% of the formulation reached deep compartments, as alveoli. In the catalytic system application, hyperbranched polyesters, similar to the employed dendrimers, were modified to incorporate peripheral -NH2 groups and used to magnify the catalytic effect of Rhodium-based catalysts. The modified hyperbranched polyesters were immobilized on magnetic nanoparticles (Fe3O4@SiO2), resulting in a high density of terminal amine groups. These groups were modified and used for the anchorage of a Rhodium catalyst. It was evaluated the increase in the metal load of the nanoparticles (from 0.2% to 1.0% w/w), as well the catalytic effect in hydroformylation reactions.

Materiais altamente especializados (polifuncionais) continuam a ser candidatos chave para avanços na área tecnológica e biológica. Buscando aplicação em campos diversos, foram sintetizadas estruturas dendríticas (dendrímeros e polímeros hiperramificados) do tipo poliéster. Esses materiais foram utilizados para dois fins distintos, a aplicação em sistemas de Drug Delivery e em sistemas catalíticos. Em relação aos sistemas de Drug Delivery, foram estudados dois aspectos principais: (i) Impregnação de fármacos na matriz dendrimérica utilizando scCO2 como solvente - foi estudado o comportamento dos materiais frente ao solvente neotério em termos de estrutura (arquitetura da macromolécula), grupos modificadores (acetonida, hidroxila, acetila e cadeia lineares de polilactato) e densidade do solvente. Os materiais que apresentaram características adequadas foram utilizados no estudo da impregnação de fármacos modelo (Ibuprofeno e Fluconazol) na matriz dendrimérica, utilizando-se scCO2 como solvente. Ambos os fármacos foram eficientemente aprisionados no interior da matriz e apresentaram interações com sua estrutra (analisadas por espectroscopia Raman e 1H RMN). (ii) Estudo do potencial para uso como nanocarreadores em Drug Delivery destinados as vias aéreas - Estudou-se o emprego dos dendrímeros do tipo poliéster de diferentes gerações (G3 e G4) modificados com um marcador fluorescente (FITC), conjugados ou não a poli(etilenoglicol) (PEG), como potenciais nanocarreadores para sistemas de Drug Delivery destinados as vias aéreas. Foram realizados testes in vitro para avaliar o transporte e a internalização desses materiais em um modelo de epitélio pulmonar (monocamada de células Calu-3). O transporte e internalização se mostraram dependentes do tamanho da espécie, sendo que dendrímeros conjugados com PEG apresentaram baixa internalização e mais eficiente transporte através da monocamada, situação oposta à ocorrida com os dendrímeros não conjugados. Estudou-se a degradabilidade desses materiais em condições de pH de relevância biológica, assim como a citotoxicidade dos dendrímeros íntegros e de seus fragmentos frente às células Calu-3, sendo que todas as espécies demonstraram baixa toxicicidade na faixa de concentração estudada. O dendrímero modificado com PEG foi utilizado em uma formulação do tipo \"pressurized metered-dose inhaler\" (pMDI). A performance do aerossol obtido com o pMDI foi avaliada, in vitro, através de um impactador de cascata de Andersen (Andersen Cascade Impactor, ACI), mostrando excelentes resultados, com ao redor de 90% da formulação atingindo regiões profundas do pulmão (eg. alvéolos). Em relação à aplicação em sistemas catalíticos, poliésteres hiperramificados, similares aos dendrímeros empregados nos demais estudos, foram modificados de modo a se obter grupos -NH2 terminais e utilizados para magnificação de performance de catalisadores baseados em ródio. Os poliésteres hiperramificados modificados foram imobilizados em nanopartículas ferromagnéticas, do tipo Fe3O4@SiO2, a fim de se obter uma elevada densidade de grupos aminos terminais, os quais foram posteriormente modificados e serviram de ancoragem para um catalisador de Rh. Foi avaliado o incremento do conteúdo de metal na nanopartícula (de 0,2% para 1,0% m/m), assim como seu efeito catalítico em reações de hidroformilação. / Highly specific materials (polyfunctional) continue to be key candidates to address the challenges of technological and biological fields. Aiming to reach different applications, polyester dendritic structures (dendrimers and hyperbranched polymers) were synthesized. These materials were used in two different ways, application in Drug Delivery systems and in catalytic systems. Regarding the usage in the Drug Delivery systems, two major aspects were studied: (i) Impregnation of drugs in the dendrimeric matrix using scCO2 as solvent - It was studied the behavior of these materials in the neoteric solvent in terms of structure (architecture of the macromolecule), modifying groups (acetonide, hydroxyl, acetyl and linear polylactide chains) and density of the solvent. The materials that showed appropriate characteristics were used for the impregnation of model drugs (Ibuprofen and Fluconazole) in the dendrimeric matrix, using scCO2 as solvent. The two drugs were efficiently trapped in the matrix, and showed interactions with its structure (analyzed by Raman Spectroscopy and 1H NMR) (ii) Study of potential usage as nanocarriers in Drug Delivery systems for the airways - It was studied the application of polyester dendrimers of different generations (G3 and G4), labeled with FITC and conjugated or not with polyethylene glycol (PEG) as potentials nanocarriers for Drug Delivery systems for the airways. In vitro tests were performed to analyze the transport and internalization of these materials in a model of lung epithelia (Calu-3 monolayer). Transport and internalization showed to be size dependent, where the PEGylated dendrimers showed low internalization and more efficient transport through the monolayer, with the opposite situation for the non-conjugated dendrimers. The degradation of the materials was studied in biological relevant values of pH, as well the cytotoxicity on Calu-3 of the dendrimers and their building-blocks. All materials showed very low cytotoxicity in the range of concentrations used. The G4 PEGylated dendrimer was used to prepare a pMDI (pressurized metered-dose inhaler) formulation. The performance of the resulting aerosol was evaluated, in vitro, using an eight stage Andersen Cascade Impactor (ACI). The results showed excellent deep lung deposition, where almost 90% of the formulation reached deep compartments, as alveoli. In the catalytic system application, hyperbranched polyesters, similar to the employed dendrimers, were modified to incorporate peripheral -NH2 groups and used to magnify the catalytic effect of Rhodium-based catalysts. The modified hyperbranched polyesters were immobilized on magnetic nanoparticles (Fe3O4@SiO2), resulting in a high density of terminal amine groups. These groups were modified and used for the anchorage of a Rhodium catalyst. It was evaluated the increase in the metal load of the nanoparticles (from 0.2% to 1.0% w/w), as well the catalytic effect in hydroformylation reactions.

Object of this thesis is to find out the influence of modified particles by plasma on properties of OSB board bonded by pMDI resin. Particles were made from veneer, because it is easier to modify by plasma (DCSBD). Produced particles were tested for chosen physical and mechanical properties. Results show degradation of properties of modified boards