MAGALHÃES JÚNIOR, Guilherme Augusto. Esferas de goma do cajueiro e quitosana para liberação de fármacos. 2007. 98 f. Dissertação (Mestrado em química)- Universidade Federal do Ceará, Fortaleza-CE, 2007. / Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-06-07T17:48:50Z No. of bitstreams: 1 2007_dis_gamagalhaesjunior.pdf: 2806397 bytes, checksum: ecc1ce90d7203c38944d44888d276ba9 (MD5) / Approved for entry into archive by José Jairo Viana de Sousa (jairo@ufc.br) on 2016-06-21T17:27:44Z (GMT) No. of bitstreams: 1 2007_dis_gamagalhaesjunior.pdf: 2806397 bytes, checksum: ecc1ce90d7203c38944d44888d276ba9 (MD5) / Made available in DSpace on 2016-06-21T17:27:44Z (GMT). No. of bitstreams: 1 2007_dis_gamagalhaesjunior.pdf: 2806397 bytes, checksum: ecc1ce90d7203c38944d44888d276ba9 (MD5) Previous issue date: 2007 / Cashew gum based beads were produced through interpenetrating polymer networks and polyelectrolyte complexation techniques. Beads of chitosan (CH) and cashew gum (CG)/CH were further crosslinked with genipin obtained from “genipapo” fruits. This crosslinking agent was characterized by proton and carbon nuclear magnetic resonance and infrared spectroscopy. Beads of CH and CH/CG were doped with sodium diclofenac and characterized by Fourier Transform Infrared spectroscopy and Electron Microscopy. Beads degree of swelling and the drug release kinetics were also determined. It was found that CH/CG beads contained up to 83 % CG and maximum swelling occurred at pH 1.2. The higher the crosslinking density, the lower were the swelling degree and the diffusion coefficient. Moreover, drug release was also found to decrease with increasing crosslinking density and no drug release occurred at pH 7.4 for CH/CG beads crosslinked with genipin, although non-crossliked bead did release the drug at that pH. CH/CG beads drug release was found to follow a non-Fickian mechanism. Polyelectrolyte complexes of chitosan and carboxymethylated cashew gum (CCM) in beads form were also investigated regarding the effects of molar mass and degree of substitution of CCM on the swelling degree and on bovine serum albumin (BSA) release. Data obtained revealed that both of molar mass and degree of substitution affect beads swelling degree and water diffusion coefficient. / Esferas à base de goma do cajueiro foram produzidas utilizando como técnicas a formação de redes interpenetradas e a complexação polieletrolítica. Esferas de quitosana (QT) e quitosana/goma do cajueiro (QT/GC) sintetizadas via formação de redes interpenetradas foram reticuladas com genipina. A genipina foi isolada a partir do fruto do jenipapo e caracterizada por espectroscopia de infravermelho e RMN de 1H e 13C. As esferas de quitosana (QT) e quitosana/goma do cajueiro (QT/GC) reticuladas com genipina foram caracterizadas por: ensaio de intumescimento, ensaio de liberação, microscopia eletrônica de varredura e espectroscopia de absorção na região do infravermelho. Pelo método do açúcar total verificou-se que 83% da goma foi incorporada às esferas. Os ensaios de intumescimento indicam que as esferas de QT/GC reticuladas têm intumescimento máximo em pH 1,2. O aumento da concentração da genipina na reticulação das esferas faz com que ocorra uma diminuição na taxa de intumescimento devido ao aumento do grau de reticulação. O coeficiente de difusão diminui com o aumento da densidade de reticulação para as esferas de QT e QT/GC. Nos ensaios de liberação constatou-se que em tampão pH 7,4 que as esferas sem reticulação são capazes de intumescer e liberar o fármaco (diclofenaco de sódio), porem não ocorreu liberação de fármaco em esferas de QT/GC reticuladas com genipina neste meio. As esferas de QT/GC reticuladas com genipina liberam diclofenaco de sódio em solução de pH 1,2 e a liberação do fármaco é inversamente proporcional à concentração de agente reticulante. A liberação de fármaco em esferas QT/GC ocorre por um mecanismo não Fickiano. Complexos polieletrolíticos de quitosana e goma do cajueiro carboximetilada (CCM) na forma de esferas também foram estudadas avaliando-se o efeito da massa molar da quitosana e do grau de substituição (GS) da goma do cajueiro carboximetilada no grau de intumescimento e liberação de albumina sérica bovina (BSA). A massa molar da quitosana e o GS da goma carboximetilada influenciam a cinética de intumescimento e o coeficiente de difusão de água nas esferas. Entretanto, na liberação do fármaco o fator mais importante na modulação da liberação é o grau de substituição da goma carboximetilada.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Esferas à base de goma do cajueiro foram produzidas utilizando como tÃcnicas a formaÃÃo de redes interpenetradas e a complexaÃÃo polieletrolÃtica. Esferas de quitosana (QT) e quitosana/goma do cajueiro (QT/GC) sintetizadas via formaÃÃo de redes interpenetradas foram reticuladas com genipina. A genipina foi isolada a partir do fruto do jenipapo e caracterizada por espectroscopia de infravermelho e RMN de 1H e 13C. As esferas de quitosana (QT) e quitosana/goma do cajueiro (QT/GC) reticuladas com genipina foram caracterizadas por: ensaio de intumescimento, ensaio de liberaÃÃo, microscopia eletrÃnica de varredura e espectroscopia de absorÃÃo na regiÃo do infravermelho. Pelo mÃtodo do aÃÃcar total verificou-se que 83% da goma foi incorporada Ãs esferas. Os ensaios de intumescimento indicam que as esferas de QT/GC reticuladas tÃm intumescimento mÃximo em pH 1,2. O aumento da concentraÃÃo da genipina na reticulaÃÃo das esferas faz com que ocorra uma diminuiÃÃo na taxa de intumescimento devido ao aumento do grau de reticulaÃÃo. O coeficiente de difusÃo diminui com o aumento da densidade de reticulaÃÃo para as esferas de QT e QT/GC. Nos ensaios de liberaÃÃo constatou-se que em tampÃo pH 7,4 que as esferas sem reticulaÃÃo sÃo capazes de intumescer e liberar o fÃrmaco (diclofenaco de sÃdio), porem nÃo ocorreu liberaÃÃo de fÃrmaco em esferas de QT/GC reticuladas com genipina neste meio. As esferas de QT/GC reticuladas com genipina liberam diclofenaco de sÃdio em soluÃÃo de pH 1,2 e a liberaÃÃo do fÃrmaco à inversamente proporcional à concentraÃÃo de agente reticulante. A liberaÃÃo de fÃrmaco em esferas QT/GC ocorre por um mecanismo nÃo Fickiano. Complexos polieletrolÃticos de quitosana e goma do cajueiro carboximetilada (CCM) na forma de esferas tambÃm foram estudadas avaliando-se o efeito da massa molar da quitosana e do grau de substituiÃÃo (GS) da goma do cajueiro carboximetilada no grau de intumescimento e liberaÃÃo de albumina sÃrica bovina (BSA). A massa molar da quitosana e o GS da goma carboximetilada influenciam a cinÃtica de intumescimento e o coeficiente de difusÃo de Ãgua nas esferas. Entretanto, na liberaÃÃo do fÃrmaco o fator mais importante na modulaÃÃo da liberaÃÃo à o grau de substituiÃÃo da goma carboximetilada / Cashew gum based beads were produced through interpenetrating polymer networks and polyelectrolyte complexation techniques. Beads of chitosan (CH) and cashew gum (CG)/CH were further crosslinked with genipin obtained from âgenipapoâ fruits. This crosslinking agent was characterized by proton and carbon nuclear magnetic resonance and infrared spectroscopy. Beads of CH and CH/CG were doped with sodium diclofenac and characterized by Fourier Transform Infrared spectroscopy and Electron Microscopy. Beads degree of swelling and the drug release kinetics were also determined. It was found that CH/CG beads contained up to 83 % CG and maximum swelling occurred at pH 1.2. The higher the crosslinking density, the lower were the swelling degree and the diffusion coefficient. Moreover, drug release was also found to decrease with increasing crosslinking density and no drug release occurred at pH 7.4 for CH/CG beads crosslinked with genipin, although non-crossliked bead did release the drug at that pH. CH/CG beads drug release was found to follow a non-Fickian mechanism. Polyelectrolyte complexes of chitosan and carboxymethylated cashew gum (CCM) in beads form were also investigated regarding the effects of molar mass and degree of substitution of CCM on the swelling degree and on bovine serum albumin (BSA) release. Data obtained revealed that both of molar mass and degree of substitution affect beads swelling degree and water diffusion coefficient

Thesis (PhD (Process Engineering))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The ongoing trend in papermaking industries is to lower production costs by increasing the low cost filler content in the sheets. However, the disruption of inter-fibre bonding is accompanied by a deterioration of paper stiffness and mechanical properties if filler content exceeds 18 wt%. Polysaccharide solutions, such as starch, are often used as a low cost biodegradable additive to improve internal sheet strength when added to the wet-end of production. The amount of starch that can be added is however limited as only a small percentage will be retained in the paper web. A dual additive multifunctional polysaccharide system was developed to allow higher filler loading levels without detrimental deterioration in paper properties. In order to achieve a larger surface area for fibre/filler interaction and to reduce drainage losses, at least one of these additives was in particulate form. Anionic, cationic, and unsaturated derivatives were prepared using sodium monochloroacetate, 3-chloro-2-hydroxypropyltrimethylammonium chloride, and allyl bromide, respectively. The degree of substitution was determined by 1H-NMR spectroscopy and back titration methods and the interaction of the ionic modified derivatives with paper components was determined using fluorescence microscopy. Anionic modified polysaccharide particles were prepared using techniques such as macrogel ultrasonification, water-in-water emulsification, and in-situ cross-linking and carboxymethylation of granular starch. A process of adding sequential layers of oppositely charged polyelectrolyte layers onto the filler particles was also investigated. A novel approach of preparing modified particles with tailored size and distribution using microfluidics was studied and modelled using response surface methodology. Hand sheets were prepared using the dual additive system and improvements in stiffness, tear resistance, breaking length, and folding endurance were observed. The modified granular maize starch particles had a pre-eminent effect on improving stiffness at higher filler loadings (14% improvement at 30 wt% filler loading), while bulky particles prepared using microfluidics showed a more consistent improvement (between 6% and 10%) across the loading range. Overall improvements gained by the introduction of multi-layered soluble polymers onto fillers suggest that the introduction of nanotechnology to the papermaking process should be of potential benefit to the industry. Furthermore, the dual additive system developed during the course of this study should also be tested on a continuous pilot plant papermaking process. / AFRIKAANSE OPSOMMING: Die papierindustrie neig voortdurend daarna om produksiekostes te verlaag deur die persentasie lae koste vulstof wat gebruik word te verhoog. Aangesien die vulstof vesel kontak belemmer, gaan hoër vlakke (> 18 wt%) egter gepaard met ’n verlaging in papier styfheid en meganiese eienskappe. Polisakkaried oplossings, soos byvoorbeeld stysel, word dikwels gebruik as lae koste vergaanbare bymiddel om papier intern te versterk wanneer dit voor die vormingsproses bygevoeg word. Slegs ’n beperkte hoeveelheid stysel word egter behou in die papier matriks en oormatige oplossings ontsnap tydens dreinering in die afvalwater. ’n Dubbele multi-funksionele polisakkaried bymiddelsisteem was ontwikkel wat ongewensde verwakking in papiereienskappe verminder tydens vulstof verhogings. Ten minste een van die bymiddels was in partikelvorm om sodoende ’n groter oppervlak te bied vir vesel/vulstof interaksie en om dreineringsverliese te verminder. Anioniese, kationiese, sowel as onversadigde derivate was berei deur onderskeidelik gebruik te maak van natrium monochloroasetaat, 3-chloro-2-hidroksiepropieltrimetielammonium chloried, en alliel bromied. Die graad van substitutiese was bepaal met behulp van 1H-KMR spektroskopie sowel as titrasie tegnieke terwyl die ioniese interaksie van die gemodifiseerde stysels met die papierkomponente ondersoek was met behulp van fluoressensie mikroskopie. Anioniese polisakkaried partikels was berei met tegnieke soos makro-jel ultrasonifikasie, water-in-water emulsifikasie, en in-situ kruisbinding en karboksiemetielasie van stysel granulate. ’n Proses was ook ondersoek waar vulstof partikels omhul was in verskeie lae poliëlektroliet oplossings. ’n Nuwe benadering was toegepas waar gemodifiseerde partikels met voorafbepaalde grootte en verspreiding berei is deur gebruik te maak van mikrofluïdika en gemodelleer met behulp van oppervlakte ontwerp metodeleer. Papier toetse was uitgevoer met die bymiddelsisteem en algehele verbetering in styfheid, skeurweerstand, breeklengte, en voulydsaamheid is waargeneem. Die gemodifiseerde stysel granulate het die grootste verbetering in styfheid by hoë vulstofladings getoon (14% verbetering by 30 wt% vulstoflading) terwyl die groter mikrofluïdika-bereide partikels algehele verbetering (tussen 6% en 10%) getoon het oor die hele vulstoflading reeks. Die verbeteringe in styfheid sowel as meganiese eienskappe van papier voorberei met poliëlektroliet omhulde vulstof toon dat aanwending van nanotegnologie in hierdie bedryf potensieel voordelig kan wees. Opskalering van die polisakkaried bymiddels ontwikkel gedurende hierdie studie behoort uitgevoer te word vir verdere toetse op ’n kontinue papier loodsaanleg.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-01-31T12:37:20Z No. of bitstreams: 1 arquivototal.pdf: 2719783 bytes, checksum: 00456e5b8ca69f853baec641a28cd6f2 (MD5) / Made available in DSpace on 2017-01-31T12:37:20Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2719783 bytes, checksum: 00456e5b8ca69f853baec641a28cd6f2 (MD5) Previous issue date: 2016-04-01 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The β-D-glucans are polysaccharides constituting the cell wall of yeasts such as Saccharomyces cerevisiae. Evidence shows polymers have several beneficial effects, mainly related to immunomodulation. However, their action on platelet and endothelial function is understudied. This study aimed to evaluate the effect of (1-3) (1-6) β-D-glucan extracted from S. cerevisiae and derivative carboxymethylated (CM-G) on vascular and platelet function in rats. The animals were treated orally with CM-G and BG-Sc at a dose of 20 mg/kg daily for eight days and the controls received saline as placebo. At end, were collected blood and thoracic aortic artery to study platelet activation and aggregation by light transmission, flow cytometry, vascular reactivity and cytokine assay. In vitro studies of platelet activation and aggregation induced by adenosine diphosphate (ADP) and collagen were conducted with CM-G at different concentrations (100 and 300 μg/mL). Significant reduction in IL-8 levels (4,18 ± 0,72 pg/mL) in the group treated with CM-G was also found when compared to control (22,7 ± 6,9 pg/mL) and the BG-Sc group (16,4 ± 2,4 pg/mL). The reactivity studies shows BG-Sc and CM-G had no influence on vascular response to phenylephrine (PHE) compared to the control. In the group treated with BG-SC, the response to vasorelaxantes agents such as acetylcholine (ACH; Emax = 90,2 ± 14,1%; pD2 = 6,36 ± 0,30 M) and sodium nitroprusside (SNP; Emax = 92,3 ± 2,4%; pD2 = 10,21 ± 0,10M) were impaired compared to controls (ACH: Emax = 100 ± 7,5%; pD2 = 8,17 ± 0,25 M; SNP: Emax = 100 ± 9,5%; pD2 = 11,18 ± 0,27 M). However, treatment with CM-G (max = 93,1 ± 2,7%; pD2 = 11,71 ± 0,07 M) increased the potency of NPS when compared with the control (Emax = 100 ± 9.5%; pD2 = 11.18 ± 0.27). In vitro studies of platelet aggregation by light transmission reveals CM-G inhibited the aggregation stimulated by ADP in doses of 100 and 300 mg/ml, reaching 25,7 ± 2,7% and 14,8 ± 3,2% of aggregation, respectively. When aggregation was induced by collagen, only the dose 300 mg/ml had inhibitory activity (33 ± 6,2%). The antiplatelet effect was similar to acetylsalicylic acid when the aggregation was generate by ADP. Aggregation inhibition was also demonstrated by flow cytometry, however was observed that CM-G had no effect on platelet activation. In treated animals, there was inhibition of platelet aggregation induced by ADP (45% ± 3,9 and 45 ± 6%, respectively). However, when induced by collagen, antiplatelet effect was observed only in animals receiving the BG-Sc (22,6 ± 7,7%). The treatment and in vitro aggregation assays suggest that CM-G appears to be more selective for ADP. The findings indicate the CM-G and BG-Sc feature antiplatelet effect and modulating vascular function. Thus, the use of these polysaccharides may be a possible tool for the prevention of cardiovascular diseases / As β-D-glucanas são polissacarídeos constituintes da parede celular de leveduras, como a Saccharomyces Cerevisae. Evidências mostram que esses polímeros possuem diversos efeitos benéficos, principalmente relacionados a imunomodulação. Entretanto, a sua ação sobre a função plaquetária e endotelial é pouco estudada. Assim, este estudo teve como objetivo avaliar o efeito da (1-3) (1-6) β-d-glucana extraída de S. cerevisae e do seu derivado carboximetilado (CM-G) sobre a função vascular e plaquetária em ratos. Os animais foram tratados por via oral com CM-G e BG-Sc na dose de 20 mg/Kg, diariamente, durante oito dias, e os controles receberam solução salina como placebo. Ao final, foram coletados o sangue e a artéria aorta torácica para estudos de agregação e ativação plaquetária por transmissão luminosa, citometria de fluxo, reatividade vascular e dosagem de citocinas. Foram realizados estudos in vitro de agregação e ativação plaquetária induzida por adenosina difosfato (ADP) e colágeno com a CM-G em diferentes concentrações (100 e 300 μg/mL). Constatou-se redução significativa dos níveis de IL-8 (4,18±0,72 pg/mL) no grupo tratado com CM-G ao se comparar com o grupo controle (22,7±6,9 pg/mL) e com o grupo BG-Sc (16,4±2,4 pg/mL). Os estudos de reatividade mostraram que a BG-Sc e a CM-G não exerceram influência sobre a resposta vascular da fenilefrina (PHE) em relação ao controle. No grupo tratado com BG-SC, a resposta aos agentes vasorelaxantes acetilcolina (ACH; Emax = 90,2 ± 14,1%; pD2 = 6,36 ± 0,30 M) e nitroprussiato de sódio (NPS; Emax = 92,3± 2,4%; pD2 = 10,21 ± 0,10M) foram prejudicadas em relação aos controles (ACH: Emax = 100 ± 7,5%; pD2 = 8,17 ± 0,25 M; NPS: Emax = 100 ± 9,5%; pD2 = 11,18 ± 0,27 M). Porém, o tratamento com a CM-G (Emax = 93,1 ± 2,7 %; pD2 = 11,71 ± 0,07 M) aumentou a potência do NPS quando comparado com o controle (Emax = 100 ± 9,5%; pD2 = 11,18 ± 0,27 M). Os estudos de agregação plaquetária in vitro por transmissão luminosa revelam que a CM-G inibiu a agregação estimulada por ADP nas doses de 100 e 300 μg/mL, atingindo 25.7±2.7% e 14.8±3.2% de agregação, respectivamente. Quando a agregação foi induzida pelo colágeno, apenas a dose 300 μg/mL teve ação inibitória (33 ± 6,2%). O efeito antiagregante foi similar ao ácido acetilsalicílico quando a agregação foi induzida por ADP. Inibição da agregação também foi demonstrada na técnica de citometria de fluxo, porém observou-se que a CM-G não afetou a ativação plaquetária. Nos animais tratados, verificou-se inibição da agregação plaquetária induzida por ADP (45 ± 3.9% e 45 ± 6 %, respectivamente). Entretanto, quando induzido por colágeno, o efeito antiagregante foi visto apenas nos animais que receberam BG-Sc (22.6 ± 7.7%). O tratamento e os ensaios de agregação in vitro sugerem que a CM-G parece ser mais seletiva para o ADP. Os achados indicam que a CM-G e a BG-Sc apresentam efeito antiagregante e moduladora da função vascular. Assim, o uso desses polissacarídeos pode ser uma possível ferramenta para a prevenção de doenças cardiovasculares.