Local anaesthetic drugs are usually administered as symptom relieving drug formulations for the treatment of pain in superficial skin extremities. The anaesthesia is delivered into skin tissues at the site of pain because of nociceptive receptors. Concerns that exist regarding local anaesthetic drug formulations are low drug encapsulation efficiency, polydispersity of colloidal formulations, chemical interactions of released local anaesthetic drug with skin proteins and bulk viscoelastic properties. Complimenting drug formulation characteristics are the desirable rates of controlled release of drug molecules from chosen formulations pertaining to favourable in vitro skin permeation kinetics are imperative pharmaceutics based research areas because skin percutaneous delivery has distinct barrier property restrictions for passive diffusion (PD) of active molecules. Lidocaine is currently the active anaesthetic molecule of choice in local anaesthesia by clinicians because of minimum toxicity and good potency. It is a low molecular weight drug comprising of electron donating and electron withdrawing functional groups with the capacity to interact by hydrogen bonding and electrostatic interactions with several drug formulation vehicles. In this work, a naturally occurring bi-polymeric formulation was achieved with lidocaine NaCMC:gelatine hydrogel. Lidocaine NaCMC:gelatine ratio of 1:2.3 was the most favourable formulation because of faster skin permeation kinetics. Lidocaine NaCMC:gelatine 1:2.7 provided the highest drug encapsulation efficiency. This resulted in high, sustained permeation rates after adaptation of the microneedle (MN) poke and patch technique, past the stratum corneum layer of skin for quick target delivery in attaining a maximum permeation flux of near 6.0 μg/cm2/h in the hypodermis layer. Mass balance of in vitro studies using an indirect approach to quantify lidocaine permeation showed significant lidocaine permeation in skin. Subsequent vertical and horizontal (depth averaged) in vitro studies using similar MN techniques resulted in crossing minimum therapeutic level across a 10 mm radius from the epicentre of the skin sample at major reduced lag times of minutes for vertical permeation and within 0.5 hours for horizontal permeation. Furthermore, the spreadability of lidocaine NaCMC:gelatine hydrogel shows favourability in the control of droplet spreading on MN treated skin.

Stimuli-responsive polymers and self-assembling peptides represent two classes of materials with interesting properties and great potential to be used as biomaterials. The conjugation of polymer with peptide offers a way to combine the controlled chemical, mechanical, and thermal properties of polymer with the functionality of designed bioactive group. Pure hybrid materials with the characteristics of individual components or systems containing hybrid materials became attractive for applications in drug delivery and tissue engineering. This work focused on systems where the thermo-responsive properties of a polymer were combined with the gelling properties of two different ionic-complementary peptides via conjugation. The prototypical thermo-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm) was chosen due to its lower critical solution temperature (LCST) ~32°C being close to body temperature. Ionic-complementary oligo-peptides, containing the alternating hydrophobic/hydrophilic and charged/uncharged amino acids, phenylalanine (F), glutamic acid (E) and lysine (K), were selected as they are known to form β-sheet rich fibrillar networks at low concentrations. Two peptide sequences with different charge distribution were chosen: FEFEFKFK and FEFKFEFK which form self-supporting gels at ~17 and 10 mg ml-1 respectively. Polymer-peptide conjugates were used to confer self-assembling and thermo-responsive behaviour to the system.Thermo-responsive PNIPAAm-rich hydrogels were obtained by targeting different degrees of functionalisation of PNIPAAm with the self-assembling peptides. Two series of such systems were prepared by using either a thiol-modified FEFEFKFK or a thiol-modified FEFKFEFK peptide as the chain-transfer agent in the free radical polymerisation of NIPAAm. The resulting polymer/conjugate mixtures were studied by proton nuclear magnetic resonance (1H NMR). The polymer/conjugate ratios were calculated and showed that the conjugate fraction in the mixtures increased with increasing concentration of peptide used for the polymerisation. Static light scattering (SLS) and viscometry showed the aggregation of the polymer/conjugate mixtures presumably due to the presence of peptide. The values from gel permeation chromatography (GPC), which were mostly attributed to the unconjugated polymers, were higher than those obtained from 1H NMR and centrifugation for the conjugates. The polymer/conjugate mixtures formed self-supporting gels where the critical gelation concentration decreased with increasing conjugate content. Oscillatory rheology experiments confirmed gels had formed and revealed that their elastic modulus, G' varied from ~ 10 to 400 Pa depending on the sample. TEM and AFM studies proved the formation of β-sheet fibres of ~ 4.5 ± 1.5 nm in diameter. The PNIPAAm-rich hydrogels were also characterised by micro DSC to reveal their thermo-responsiveness and phase separation and showed the LCST at ~ 30°C. The results of the study showed that varying the peptide sequence did not have an effect on thermal, mechanical or morphological properties of the hydrogels. By exploiting the self-assembly of the ionic-complementary peptides, it was possible to create PNIPAAm-rich, thermo-responsive hydrogels with controllable properties.Further in the study pure PNIPAAm-FEFEFKFK conjugate was incorporated into the FEFEFKFK peptide matrix to create peptide-rich thermo-responsive composite gels. Two series of the composite gels were prepared by varying separately the peptide matrix and polymer-peptide conjugate concentration. Micro DSC measurements revealed an endothermic peak at ~ 30ºC characteristic of the LCST of PNIPAAm. Oscillatory rheology studies showed that the composite gels became stronger with increasing conjugate concentration (G' ~ 20 - 200 Pa). Network morphology was studied by SANS. Using contrast variation and contrast matching techniques it was possible to distinguish between the peptide fibres and the PNIPAAm chains. Below and above the LCST the scattering curves showed a q-1 behaviour which is typical of rod-like objects. TEM and AFM also proved the formation of fibres of ~4.0 ± 0.8 nm and ~4.5 ± 1 nm respectively. AFM studies showed that the fibres of the composite gels were decorated with polymer chains. The thermo-responsiveness and the gelation properties of these conjugate-based scaffolds have potential for use as drug delivery vehicles or tissue engineering scaffolds.

Made available in DSpace on 2016-01-26T18:56:02Z (GMT). No. of bitstreams: 1 Murilo Mendes de Angelo.pdf: 1443900 bytes, checksum: f6d656f910c3210fd63e015a55ec60a4 (MD5) Previous issue date: 2014-11-28 / The Agriculture in the Pontal do Paranapanema region is a major source of employment and income, with the highlight the cultivation of sugar cane. Along with the expansion of the cultivated area has been a substantial increase in the use of herbicides. Among the various existing herbicides in the domestic market, glyphosate, Roundup®, appears with great relevance in the agricultural scenario, because in addition to efficient has a broad spectrum of action. Moreover, their use also generates unwanted environmental impacts, such as changes in soil microbes and the generation of a taproot. Additionally, by leaching a part of glyphosate applied to crops can reach surface water, such as rivers. In the face of this problem, this study followed the process of degradation of glyphosate in a biological reactor, through the activated sludge process. Two studies, the first of which used a synthetic wastewater containing glyphosate as a source of carbon, nitrogen and phosphorus and sewage sludge. The second treatment was done under the same conditions first by adding a hydrogel polymer. These polymers are employed in the sugarcane plantations for water retention and can reach surface waters through leaching. The monitoring system was conducted through analysis of chemical oxygen demand (COD), amount of phosphorus, nitrogen, glyphosate, nitrite and nitrate, reaction temperature, pH and Dissolved Oxygen. The results demonstrate that the treatment of the effluent containing only glyphosate is more efficient than treatment containing glyphosate and the hydrogel polymer. / A agricultura na região do Pontal do Paranapanema é uma das principais fontes de emprego e de renda, tendo como destaque o cultivo da cana de açúcar. Junto com a expansão da área cultivada tem ocorrido um aumento substancial na utilização de herbicidas. Dentre os vários herbicidas existentes no mercado nacional, o glifosato, Roundup®, aparece com grande relevância no cenário agrícola, pois além de eficiente possui um amplo espectro de ação. Por outro lado, a sua utilização também acaba gerando impactos ambientais indesejados, como a alteração na microbiota do solo e a geração da raiz pivotante. Adicionalmente, através da lixiviação, uma parte do glifosato aplicado nas lavouras pode atingir as águas superficiais, como por exemplo a dos rios. Em face deste problema, o presente trabalho acompanhou o processo de degradação do glifosato, em um reator biológico, por meio do processo de lodos ativados. Dois estudos foram realizados, sendo que o primeiro utilizou um efluente sintético contendo glifosato como fonte de carbono, nitrogênio e fósforo e o lodo de esgoto. O segundo tratamento foi realizado sob as mesmas condições do primeiro, adicionando-se um polímero hidroabsorvente. Estes polímeros são empregados nas plantações canavieiras para a retenção da água e também podem atingir as águas superficiais, através da lixiviação. O monitoramento do sistema foi realizado através das análises da demanda química de oxigênio (DQO), quantidade de fósforo, de nitrogênio, do glifosato, do nitrito e do nitrato, temperatura do reator, pH e Oxigênio Dissolvido. Os resultados demostraram que o tratamento do efluente contendo apenas o glifosato é mais eficiente do que o tratamento contendo o glifosato e o polímero hidroabsorvente.

Made available in DSpace on 2016-07-18T17:46:20Z (GMT). No. of bitstreams: 1 Murilo Mendes de Angelo.pdf: 1443900 bytes, checksum: f6d656f910c3210fd63e015a55ec60a4 (MD5) Previous issue date: 2014-11-28 / The Agriculture in the Pontal do Paranapanema region is a major source of employment and income, with the highlight the cultivation of sugar cane. Along with the expansion of the cultivated area has been a substantial increase in the use of herbicides. Among the various existing herbicides in the domestic market, glyphosate, Roundup®, appears with great relevance in the agricultural scenario, because in addition to efficient has a broad spectrum of action. Moreover, their use also generates unwanted environmental impacts, such as changes in soil microbes and the generation of a taproot. Additionally, by leaching a part of glyphosate applied to crops can reach surface water, such as rivers. In the face of this problem, this study followed the process of degradation of glyphosate in a biological reactor, through the activated sludge process. Two studies, the first of which used a synthetic wastewater containing glyphosate as a source of carbon, nitrogen and phosphorus and sewage sludge. The second treatment was done under the same conditions first by adding a hydrogel polymer. These polymers are employed in the sugarcane plantations for water retention and can reach surface waters through leaching. The monitoring system was conducted through analysis of chemical oxygen demand (COD), amount of phosphorus, nitrogen, glyphosate, nitrite and nitrate, reaction temperature, pH and Dissolved Oxygen. The results demonstrate that the treatment of the effluent containing only glyphosate is more efficient than treatment containing glyphosate and the hydrogel polymer. / A agricultura na região do Pontal do Paranapanema é uma das principais fontes de emprego e de renda, tendo como destaque o cultivo da cana de açúcar. Junto com a expansão da área cultivada tem ocorrido um aumento substancial na utilização de herbicidas. Dentre os vários herbicidas existentes no mercado nacional, o glifosato, Roundup®, aparece com grande relevância no cenário agrícola, pois além de eficiente possui um amplo espectro de ação. Por outro lado, a sua utilização também acaba gerando impactos ambientais indesejados, como a alteração na microbiota do solo e a geração da raiz pivotante. Adicionalmente, através da lixiviação, uma parte do glifosato aplicado nas lavouras pode atingir as águas superficiais, como por exemplo a dos rios. Em face deste problema, o presente trabalho acompanhou o processo de degradação do glifosato, em um reator biológico, por meio do processo de lodos ativados. Dois estudos foram realizados, sendo que o primeiro utilizou um efluente sintético contendo glifosato como fonte de carbono, nitrogênio e fósforo e o lodo de esgoto. O segundo tratamento foi realizado sob as mesmas condições do primeiro, adicionando-se um polímero hidroabsorvente. Estes polímeros são empregados nas plantações canavieiras para a retenção da água e também podem atingir as águas superficiais, através da lixiviação. O monitoramento do sistema foi realizado através das análises da demanda química de oxigênio (DQO), quantidade de fósforo, de nitrogênio, do glifosato, do nitrito e do nitrato, temperatura do reator, pH e Oxigênio Dissolvido. Os resultados demostraram que o tratamento do efluente contendo apenas o glifosato é mais eficiente do que o tratamento contendo o glifosato e o polímero hidroabsorvente.

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