Tesis sobre el tema "Poloxamer 407"

O nimodipino é um bloqueador de canais de cálcio usado principalmente na terapia da hemorragia subaracnóidea e no tratamento de distúrbios cognitivos. É praticamente insolúvel em água e, pelo Sistema de Classificação Biofarmacêutica (SCB), é qualificado como classe II e, portanto, sua dissolução é etapa limitante da absorção, podendo apresentar problemas de biodisponibilidade. Assim, o objetivo do trabalho foi desenvolver e caracterizar dispersões sólidas de nimodipino, obtidas com os carreadores PEG 6000 ou Poloxamer 407 e compará-las quanto à melhoria na solubilidade e na dissolução do nimodipino. As dispersões sólidas foram obtidas pelos métodos de fusão e de evaporação do solvente e foram caracterizadas pelas técnicas de calorimetria exploratória diferencial (DSC), espectroscopia de absorção na região do infravermelho (FT-IR) e difração de raios-X, cujos resultados comprovaram a obtenção das dispersões sólidas. As características de solubilidade e de dissolução do nimodipino nas dispersões sólidas e em misturas físicas foram comparadas. As dispersões sólidas contendo poloxamer 407 apresentaram maior eficiência em melhorar a solubilidade e a velocidade de dissolução do nimodipino, o que pode ser explicado pelo seu efeito tensoativo. O aumento da solubilidade das dispersões sólidas preparadas com PEG (DSPEG-10 = 13,2 g.mL-1) foi significativamente maior que aquele devido às misturas físicas de mesma composição (MFPEG-10 = 3,21 g.mL-1) que, por sua vez, apresentaram solubilidade maior que a do fármaco (2,19 g.mL-1). O mesmo ocorreu com a eficiência de dissolução dessas preparações (DSPEG-10 = 69,11% , MFPEG-10 = 15,61% e nimodipino = 11,68%). Maior incremento da solubilidade foi obtido com a dispersão sólida produzida pelo método de evaporação do solvente contendo poloxamer 407 como carreador (SOLVP407-10 = 75,61 g.mL-1).
Nimodipine is a calcium blocker, used in prevention and treatment of ischaemic neurological deficits after aneurismal subarachnoid hemorrhage and cognitive deficit. It exhibits a low solubility in water and it is classified as class two in the Biopharmaceutics Classification System (BCS), thereby dissolution is the ratelimiting step in absorption, which impact on bioavailability. Consequently, the objective of this study was to develop and characterize solid dispersions of nimodipine, prepared with PEG 6000 or Poloxamer 407 and to compare them in terms of nimodipine solubility and dissolution. Solid dispersions were obtained by fusion and solvent methods and they were characterized by differential scanning calorimetry (DSC), infra red spectroscopy (FT-IR) and X-ray diffraction, where results confirmed the formation of solid dispersions. Solubility and dissolution characteristics of nimodipine in solid dispersions and physical mixtures were compared. Solid dispersions containing poloxamer 407 showed better efficiency than PEG in increasing solubility and dissolution rate of nimodipine, and it can be explained due to its surfactant activity. The solubility results obtained with solid dispersions prepared with PEG 6000 (DSPEG-10 = 13,2 g.mL-1) were better than physical mixtures with the same composition (MFPEG-10 = 3,21 g.mL-1) which, in turn, showed increased solubility compared with nimodipine (2,19 g.mL-1). Similar results were observed for dissolution efficiency (DSPEG-10 = 69,11% , MFPEG-10 = 15,61% and nimodipine = 11,68%). The best solubility result was obtained by the formulation prepared by the solvent method with poloxamer 407 as carrier (SOLVP407-10 = 75,61 g.mL-1).

Made available in DSpace on 2017-07-21T14:13:13Z (GMT). No. of bitstreams: 1 Fabiula Franke.pdf: 1832049 bytes, checksum: 9f31a658c71b761b6dda69c029bbafb4 (MD5) Previous issue date: 2014-02-26
The ferulic acid has antioxidant, anti-inflammatory, antithrombotic, anticancer, neuroprotective, cardioprotective and photoprotective activity. However, despite these biological activities, its therapeutic usefulness is limited due to certain unfavorable physicochemical properties, especially the low aqueous solubility. It is classified as a Class II drug by the Biopharmaceutical Classification System and therefore its dissolution is a limiting step of absorption, may present bioavailability problems. Thus, considering the large number of pharmacological properties attributed to ferulic acid, the aim of this study was to develop and characterize solid dispersions containing ferulic acid, hydrophobic, a non-ionic surfactant (Poloxamer 407) and compare them in terms of improving the dissolution of ferulic acid. Solid dispersions were obtained by methods of crushing, kneading, co-evaporation, fusion, spray drying and freeze drying at concentrations of 10 and 20%. The formulations showed a yield between 38.6 and 80.2%. All formulations showed adequate amounts of efficiency of incorporation, greater than 80%. The solid dispersions were characterized by scanning electron microscopy, X-ray diffraction and spectroscopy in the infrared region in Fourier transform, whose results confirmed the acquisition of solid dispersions. The dissolution characteristics of the pure drug and the formulations were compared. Solid dispersions exhibited greater efficiency in improving the speed of dissolution of the ferulic acid, explainable by the effect of Poloxamer 407 surfactant. A highest increase of dissolving was obtained with the formulation obtained by the method of freeze drying at a concentration of 10%, with dissolution efficiency of 93.83%. The dissolution profiles showed the best fit to a monoexponential equation. These results suggest that the solid dispersions prepared with the use of Poloxamer 407, containing the drug, are strategies feasible in the pharmaceutical industry.
O ácido ferúlico tem atividade antioxidante, anti-inflamatória, antitrombótica, anticancerígena, neuroprotetora, cardioprotetora e fotoprotetora. No entanto, apesar dessas atividades biológicas, sua utilidade terapêutica é limitada devido a certas propriedades físico-químicas desfavoráveis, notadamente a baixa solubilidade aquosa. É qualificado como fármaco da Classe II pelo Sistema de Classificação Biofarmacêutica e, portanto, sua dissolução é etapa limitante da absorção, podendo apresentar problemas de biodisponibilidade. Assim, considerando o elevado número de propriedades farmacológicas atribuídas ao ácido ferúlico, o objetivo desse trabalho foi desenvolver e caracterizar dispersões sólidas contendo ácido ferúlico, hidrofóbico, e um surfactante não-iônico Poloxamer 407 e compará-las quanto à melhoria na dissolução do ácido ferúlico. As dispersões sólidas foram obtidas pelos métodos de trituração, malaxagem, coevaporação, fusão, liofilização e spray-drying nas concentrações de 10 e 20%. As formulações apresentaram um rendimento entre 38,6 e 80,2%. Todas as formulações mostraram valores de eficiência de incorporação adequados, superiores a 80%. As dispersões sólidas foram caracterizadas por microscopia eletrônica de varredura, por difração de raios X e por espectroscopia na região do infravermelho com transformada em Fourier, cujos resultados comprovaram a obtenção das dispersões sólidas. As características de dissolução entre o fármaco puro e as formulações foram comparadas. As dispersões sólidas apresentaram maior eficiência em melhorar a velocidade de dissolução do ácido ferúlico, explicável pelo efeito tensoativo do Poloxamer 407. Maior incremento da dissolução foi obtido com a formulação obtida pelo método de liofilização na concentração de 10%, com eficiência de dissolução de 93,83%. Os perfis de dissolução apresentaram o melhor ajuste para a equação monoexponencial. Esses resultados sugerem que as dispersões sólidas elaboradas com o uso do Poloxamer 407, contendo o fármaco, são estratégias viáveis na indústria farmacêutica.

La gonococcie est une infection sexuellement transmissible due au gonocoque. Elle est devenue un problème majeur de santé publique du fait de la multirésistance aux antibiotiques, mais surtout de la résistance au traitement de dernière intention actuellement en vigueur. Lactobacillus crispatus, une bactérie naturelle, commensale du vagin de la femme, s’est montré efficace pour inhiber le gonocoque. Les gels, une forme galénique bien acceptée, sont déjà utilisés pour le traitement des infections genitales de la femme. Disposer d’un gel contenant Lactobacillus crispatus, efficace, facile à administrer par la femme elle-même parait donc attractif pour la prévention de la gonococcie. Ainsi, nous avons conçu un gel à base d’un polymère thermogélifiant, le poloxamer 407 et d’un polymère biocompatible, l’alginate de sodium. Dans un premier temps, une étude physico-chimique du mélange de polymères a permis de retenir les concentrations optimisées. Dans un second temps, la souche de Lactobacillus choisie a été caractérisée et introduite dans le mélange de polymères. Les propriétés physicochimiques dont les caractéristiques rhéologiques, l’expulsion d’un dispositif d’administration, la stabilité, la microstructure ainsi que l’efficacité in vitro du gel obtenu ont été étudiés. Une répartition homogène de Lactobacillus crispatus a été observée dans le gel. Ce système est facilement administrable et possède des propriétés rhéologiques favorables à son étalement et son maintien dans la lumière vaginale. Ce gel a permis d’inhiber la croissance du gonocoque in vitro
Gonorrhea is a sexually transmitted infection caused by Neisseria gonorrhoeae. It has become a major public health issue due to multidrug resistance, especially resistance to the current last-intention treatment.Lactobacillus crispatus, a natural bacterium, commensal to the woman's vagina, has been shown to inhibit Neisseria gonorrhoeae. Gels, a well-accepted dosage form, are already used for the treatment of woman's genital infections. Having a gel containing Lactobacillus crispatus, that is effective, easy to administer by the woman herself, would be ideal for the prevention of gonorrhea. Thus, we designed a gel based on a thermogelling polymer, poloxamer 407, and a biocompatible polymer, sodium alginate. First, a physicochemical study of the polymers mixtures allowed to select the optimized concentrations. Second, the selected Lactobacillus strain was characterized and introduced into the optimized polymer mixture. Physicochemical properties including rheological characteristics, expulsion from a device, stability, microstructure as well as in vitro gel efficacy were studied. A homogeneous distribution of Lactobacillus crispatus was observed in the gel. It was easily administered and its rheological properties were suitable for its spreading and its long reidence time in the vaginal lumen. This gel showed an inhibition of gonococcal growth in vitro

Le traitement des infections sur corps etranger demeure un probleme preoccupant, notamment en chirurgie orthopedique. La vancomycine et la gentamicine occupent chacune une place importante dans le traitement de ce type d'infection. Ce travail evalue la faisabilite et l'efficacite de l'administration locale de ces antibiotiques a l'interieur d'une matrice de poloxamer 407. Les proprietes rheologiques particulieres de ce vehicule permettent son administration sous forme liquide directement au site recherche, et sa gelification in situ a la temperature corporelle. L'association de l'antibiotique au poloxamer n'alterait ni l'activite anti-infectieuse de l'antibiotique, ni les proprietes physiques du gel. L'etude des proprietes diffusionnelles de cette association a montre une liberation prolongee de l'agent anti-infectieux tant in vitro qu'in vivo, chez l'animal sain et infecte. L'adherence bacterienne est une etape primordiale de la colonisation de la surface d'un corps etranger, elle est suivie de la formation d'un biofilm qui enveloppe et protege les germes des defenses de l'hote et de l'activite des antibiotiques. In vitro, nos resultats ont montre que le poloxamer 407 agit de deux manieres sur le developpement de s. Aureus et s. Epidermidis a la surface d'un corps etranger : en diminuant le nombre de bacteries adherentes, et en restaurant la sensibilite des bacteries adherentes residuelles a l'activite des antibiotiques. In vivo, sur un modele d'infection a s. Aureus sur cage tissulaire chez le cobaye, l'administration locale d'une association vancomycine / poloxamer 407 a permis d'inhiber l'adhesion des bacteries au corps etranger et de steriliser le site d'inoculation. Ces donnees suggerent que le poloxamer 407 est un vehicule adapte pour une antibiotherapie locale, particulierement au niveau de zones faiblement vascularisees et/ou lors de l'utilisation d'antibiotiques a faible index therapeutique.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior
As dislipidemias e a obesidade sÃo distÃrbios cuja prevalÃncia vem aumentando no Brasil e no mundo, e sÃo extremamente importantes do ponto de vista da saÃde pÃblica, pois ambas desempenham um importante papel no cenÃrio das doenÃas cardiovasculares. Por terem cunho inflamatÃrio, trazem danos oxidativos aos tecidos e ÃrgÃos, comprometendo seu funcionamento. O Ãleo de coco extra virgem (OCEV), extraÃdo do fruto do coqueiro (Cocos nucifera L.), o coco, à uma gordura saturada rica em Ãcidos graxos de cadeia mÃdia e compostos polifenÃlicos, os quais evidenciaram atividades antimicrobiana, antitrombÃtica e antioxidante. O objetivo do presente estudo à averiguar os efeitos do Ãleo de coco extra virgem sobre o perfil bioquÃmico lipÃdico e antioxidante no tratamento da obesidade e dislipidemia em camundongos, assim como no estresse oxidativo deles decorrentes. A dislipidemia foi induzida por injeÃÃo intraperitoneal de soluÃÃo de poloxamer P-407 em camundongos machos, que foram tratados com fenofibrato ou Ãleo de coco a 3, 6 ou 12mL/Kg (P+OC3, P+OC6 e P+OC12, respectivamente) 2 e 26 horas apÃs a induÃÃo, com coleta 24 e 48 horas pÃs-induÃÃo e dosagem de glicose, triacilglicerÃis e colesterol total. A obesidade foi induzida por raÃÃo hipercalÃrica durante 15 semanas, com tratamento simultÃneo com sibutramina ou Ãleo de coco extra virgem a 5%, 7,5% ou 10% (DH+OC5, DH+OC7,5 e DH+OC10, respectivamente) em peso incorporado à raÃÃo hipercalÃrica, com dosagens de glicose, triacilglicerÃis, colesterol total, HDL e nÃo-HDL, ALT e AST. Ao fim dos protocolos, o fÃgado foi removido para dosagem dos parÃmetros antioxidantes catalase e TBARS. No protocolo de dislipidemia os nÃveis de triacilglicerÃis foram reduzidos em todos os grupos tratados com OCEV (reduÃÃo entre 68,31% e 114,8% em relaÃÃo a P). Catalase (aumento de 203%) e TBARS (reduÃÃo de 70,90%) tiveram resultados benÃficos em P+OC12 em relaÃÃo a P. Na obesidade, a glicemia e colesterol total diminuÃram em DH+OC5 (31,77% e 32,28%, respectivamente). Os nÃveis de HDL aumentaram em todos os grupos que consumiram OCEV, assim como a atividade plasmÃtica de alanina aminotransferase (ALT) (31,60% e 38,89%, respectivamente); a concentraÃÃo plasmÃtica de triacilglicerÃis reduziu-se em DH+OC7,5 (48,55%) em relaÃÃo a DH, assim como a atividade de aspartato aminotransferase (AST) aumentou em DH+OC10 (44,52%). Catalase aumentou em DH+OC5 (145,61%), e TBARS reduziu em DH+OC10 (74,15%). Conclui-se que o OCEV possui efeitos benÃficos sobre parÃmetros bioquÃmicos do perfil lipÃdico e oxidativo de camundongos dislipidÃmicos e obesos.

RODRIGUES, Hector Galdino. Avaliação dos efeitos do óleo de coco (Cocos nucifera L.) extra virgem em protocolos de indução de obesidade por dieta hipercalórica e indução de dislipidemia por poloxamer P-407 em camundongos. 2015. 103 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2015.
Submitted by denise santos (denise.santos@ufc.br) on 2016-03-03T13:29:37Z No. of bitstreams: 1 2015_dis_hgrodrigues.pdf: 1527840 bytes, checksum: b02147464dbb8be18289352d1c9d3f86 (MD5)
Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2016-03-03T14:16:34Z (GMT) No. of bitstreams: 1 2015_dis_hgrodrigues.pdf: 1527840 bytes, checksum: b02147464dbb8be18289352d1c9d3f86 (MD5)
Made available in DSpace on 2016-03-03T14:16:34Z (GMT). No. of bitstreams: 1 2015_dis_hgrodrigues.pdf: 1527840 bytes, checksum: b02147464dbb8be18289352d1c9d3f86 (MD5) Previous issue date: 2015
Dyslipidemia and obesity are disorders whose prevalence is increasing in Brazil and worldwide, and are extremely important in Public Health , as both play important role on cardiovascular diseases development . Due to its inflammatory nature, occurs oxidative damage to tissues and organs, compromising its funcionality . Extra virgin coconut oil (OCEV), extracted from the fruit of the coconut pal m (Cocos nucifera L.), coconut, is a saturated fat rich in medium chain fatty acids and polyphenolic compounds, which showed antimicrobial, antithrombotic and antioxidant activity . The aim of this study is to investigate the effects of extra virgin coconut oil on lipid and antioxidant profile in the treatment of obesity and dyslipidemia in mice as well as in their oxidative stress arising. Dyslipidemia was induced by intraperitonea l injection of poloxamer solution P - 407 in male mice that were treated with fenofibrate or coconut oil to 3, 6 or 12 mL / kg ( P+OC3, P+OC6 e P+OC12 , respectively) 2 and 26 hours after induction, with collection 24 and 48 hours post - induction and dosage of glucose, triglycerides and total cholesterol. Obesity was induced by hypercaloric diet for 15 weeks with simultaneous treatment with sibutramine or extra virgin coconut oil 5%, 7.5% or 10% ( DH+OC5, DH+OC7,5 and DH+OC10 , respectively) by weight incorporated in hypercaloric diet, with determination of glucose, triglycerides, total cholesterol, non - HDL and HDL, ALT and AST. At the end of the protocols, the liver was removed for determination of antioxidant catalase and TBARS parameters. In dyslipidemia protoco l triglycerides levels were reduced in all groups treated with OCEV (reduction from 68.31% to 114.8% relative to P). Catalase (up 203%) and TBARS (down 70.90%) had beneficial results in P + OC12 relative to P. In obesity, blood glucose and total cholestero l decreased by DH + OC5 (31.77% and 32 28%, respectively). HDL levels increased in all groups who consumed OCEV, as well as the plasma activity of alanine aminotransferase (ALT) (31.60% and 38.89%, respectively); the serum triglycerides decreased by DH + O C7,5 (48.55%) compared to HD, as well as the aspartate aminotransferase activity (AST) increased by DH + OC10 (44.52%). Catalase increased by DH + OC5 (145.61%), and TBARS decreased by DH + OC10 (74.15%). It concludes that the OCEV has beneficial effects o n oxidative and lipid profile of dyslipidemic and obese mice
As dislipidemias e a obesidade são distúrbios cuja prevalência vem aumentando no Brasil e no mundo, e são extremamente importantes do ponto de vista da saúde pública, pois ambas desempenham um importante papel no cenário das doenças cardiovasculares. Por terem cunho inflamatório, trazem danos oxidativos aos tecidos e órgãos, comprometendo seu funcionamento. O óleo de coco extra virgem (OCEV), extraído do fruto do coqueiro (Cocos nucifera L.), o coco, é uma gordura saturada rica em ácidos graxos de cadeia média e compostos polifenólicos, os quais evidenciaram atividades antimicrobiana, antitrombótica e antioxidante. O objetivo do presente estudo é averiguar os efeitos do óleo de coco extra virgem sobre o perfil bioquímico lipídico e antioxidante no tratamento da obesidade e dislipidemia em camundongos, assim como no estresse oxidativo deles decorrentes. A dislipidemia foi induzida por injeção intraperitoneal de solução de poloxamer P-407 em camundongos machos, que foram tratados com fenofibrato ou óleo de coco a 3, 6 ou 12mL/Kg (P+OC3, P+OC6 e P+OC12, respectivamente) 2 e 26 horas após a indução, com coleta 24 e 48 horas pós-indução e dosagem de glicose, triacilgliceróis e colesterol total. A obesidade foi induzida por ração hipercalórica durante 15 semanas, com tratamento simultâneo com sibutramina ou óleo de coco extra virgem a 5%, 7,5% ou 10% (DH+OC5, DH+OC7,5 e DH+OC10, respectivamente) em peso incorporado à ração hipercalórica, com dosagens de glicose, triacilgliceróis, colesterol total, HDL e não-HDL, ALT e AST. Ao fim dos protocolos, o fígado foi removido para dosagem dos parâmetros antioxidantes catalase e TBARS. No protocolo de dislipidemia os níveis de triacilgliceróis foram reduzidos em todos os grupos tratados com OCEV (redução entre 68,31% e 114,8% em relação a P). Catalase (aumento de 203%) e TBARS (redução de 70,90%) tiveram resultados benéficos em P+OC12 em relação a P. Na obesidade, a glicemia e colesterol total diminuíram em DH+OC5 (31,77% e 32,28%, respectivamente). Os níveis de HDL aumentaram em todos os grupos que consumiram OCEV, assim como a atividade plasmática de alanina aminotransferase (ALT) (31,60% e 38,89%, respectivamente); a concentração plasmática de triacilgliceróis reduziu-se em DH+OC7,5 (48,55%) em relação a DH, assim como a atividade de aspartato aminotransferase (AST) aumentou em DH+OC10 (44,52%). Catalase aumentou em DH+OC5 (145,61%), e TBARS reduziu em DH+OC10 (74,15%). Conclui-se que o OCEV possui efeitos benéficos sobre parâmetros bioquímicos do perfil lipídico e oxidativo de camundongos dislipidêmicos e obesos.

Le principali forme farmaceutiche per uso oftalmico sono rappresentate dai colliri grazie alla loro semplicità di preparazione, sterilizzazione e somministrazione. Tuttavia, i colliri presentano una bassa biodisponibilità di circa il 5%. Ottimi risultati si sono ottenuti con l’utilizzo di sistemi di veicolazione di farmaci a base lipidica caratterizzati da elevata biocompatibilità. La nostra attenzione è stata rivolta all’utilizzo di due diverse molecole con potente potenziale antiossidante, l’Epigallocatechina-3-gallato (EGCG) e l’Edaravone, le quali hanno dimostrato la loro efficacia nel trattamento e/o prevenzione delle patologie oculari associate allo stress ossidativo. L’obbiettivo finale è lo sviluppo di un sistema di veicolazione di farmaci stabile ed efficiente considerando 3 punti fondamentali: (a) Massimizzare la quantità di farmaco inglobata nel sistema di trasporto lipidico al fine aumentare la quantità di molecola che giunge al sito target. ( b) Stabilità colloidale e caratterizzazione dei sistemi di trasporto. (c) Abilità di proteggere le cellule retinale dalla morte cellulare indotta dallo stress ossidativo. Dai risultati ottenuti possiamo concludere che la percentuale di inglobamento della molecola EGCG risente dell’effetto salino e della composizione lipidica. In particolare, l’utilizzo di MgCl2 in combinazione con una matrice anionica ed, in presenza del Poloxamer-407, ci ha permesso di ottenere un sistema altamente stabile caratterizzato dal 100% di inglobamento. Questo sistema si è dimostrato capace di proteggere le cellule retinali dallo stress ossidativo in misura maggiore rispetto alla molecola veicolata tal quale. L’utilizzo di concentrazioni crescenti ci ha permesso di aumentare l’inglobamento dell’EGCG all’interno di fasi cubiche ed esagonali, altri sistemi di veicolazione di farmaci usati in campo oftalmico. La struttura di tutti i sistemi studiati è stata caratterizzata mediante esperimenti di diffrazione a raggi x e neutroni. Inoltre, l’introduzione di gruppi lipofili costituiti da catene di C-18, oltre a permettere il completo inglobamento delle molecole studiate, ha aumentato la loro capacità di proteggere le cellule retinale dalla morte indotta dallo stress ossidativo.
This thesis presents an extended work concerning the development of lipid-based systems able to prevent and control the ocular diseases associated with oxidative stress. The eye drops dosage forms account for nearly 90% of currently available marketed formulations thanks of their simplicity, safety and acceptance by patients. However, the bioavailability of topically applied drugs is about 5%. The lipid-based nanocarriers, which are highly biocompatible, can carry the antioxidant to the specific site. Among the antioxidants used for ophthalmic applications, the attention was focused on Epigallocatechin-3-gallate and Edaravone molecules, which are well-known for being bioactive in ocular diseases associated with oxidative stress. Since the final aim was to create a stable and efficient delivery system, the design of lipid-based nanocarriers has been based on three critical targets: a) High encapsulation efficiency in order to optimize the delivery of the active principle at the target sites. b) Colloidal stability and characterization of lipid-based systems. c) Ability to protect the retinal cells from oxidative stress-induced cell death. From the obtained results, we concluded that the encapsulation percentage of EGCG inside liposomes showed specific ion effects together with influence of the lipid matrix composition. More in details, the combination of magnesium chloride, anionic matrix and Poloxamer-407 allow us to obtain a system highly stable with 100% EGCG encapsulation that was able to protect retinal cells from oxidative stress. Using increasing concentrations of EGCG we optimized the encapsulation efficiency of catechin inside the cubic and hexagonal phase, others interesting systems used in the ophthalmic field. The structures of all systems were characterized by X-Ray and Neutrons experiments. In addition, the introduction of lipophilic C-18 chain in EGCG and Edaravone molecules also increased their encapsulation efficiency inside a liposomal vector as well as their ability to protect the retinal cells from oxidative stress.

Owing to its strategic position in the liver sinusoid, pathologic and morphologic alterations of the Liver Sinusoidal Endothelial Cell (LSEC) have far-reaching repercussions for the whole liver and systemic metabolism. LSECs are perforated with fenestrations, which are pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Loss of LSEC porosity is termed defenestration, which can result from loss of fenestrations and/ or decreases in fenestration diameter. Gram negative bacterial endotoxin (Lipopolysaccharide, LPS) has marked effects on LSEC morphology, including induction LSEC defenestration. Sepsis is associated with hyperlipidemia, and proposed mechanisms include inhibition of tissue lipoprotein lipase and increased triglyceride production by the liver. The LSEC has an increasingly recognized role in hyperlipidemia. Conditions associated with reduced numbers of fenestrations such as ageing and bacterial infections are associated with impaired lipoprotein and chylomicron remnant uptake by the liver and consequent hyperlipidemia. Given the role of the LSEC in liver allograft rejection and hyperlipidemia, changes in the LSEC induced by LPS may have significant clinical implications. In this thesis, the following major hypotheses are explored: 1. The Pseudomonas aeruginosa toxin pyocyanin induces defenestration of the LSEC both in vitro and in vivo 2. The effects of pyocyanin on the LSEC are mediated by oxidative stress 3. Defenestration induced by old age and poloxamer 407 causes intrahepatocytic hypoxia and upregulation of hypoxia-related responses 4. Defenestration of the LSEC seen in old age can be exacerbated by diabetes mellitus and prevented or ameliorated by caloric restriction commencing early in life

Doctor of Philosophy(PhD)
Owing to its strategic position in the liver sinusoid, pathologic and morphologic alterations of the Liver Sinusoidal Endothelial Cell (LSEC) have far-reaching repercussions for the whole liver and systemic metabolism. LSECs are perforated with fenestrations, which are pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Loss of LSEC porosity is termed defenestration, which can result from loss of fenestrations and/ or decreases in fenestration diameter. Gram negative bacterial endotoxin (Lipopolysaccharide, LPS) has marked effects on LSEC morphology, including induction LSEC defenestration. Sepsis is associated with hyperlipidemia, and proposed mechanisms include inhibition of tissue lipoprotein lipase and increased triglyceride production by the liver. The LSEC has an increasingly recognized role in hyperlipidemia. Conditions associated with reduced numbers of fenestrations such as ageing and bacterial infections are associated with impaired lipoprotein and chylomicron remnant uptake by the liver and consequent hyperlipidemia. Given the role of the LSEC in liver allograft rejection and hyperlipidemia, changes in the LSEC induced by LPS may have significant clinical implications. In this thesis, the following major hypotheses are explored: 1. The Pseudomonas aeruginosa toxin pyocyanin induces defenestration of the LSEC both in vitro and in vivo 2. The effects of pyocyanin on the LSEC are mediated by oxidative stress 3. Defenestration induced by old age and poloxamer 407 causes intrahepatocytic hypoxia and upregulation of hypoxia-related responses 4. Defenestration of the LSEC seen in old age can be exacerbated by diabetes mellitus and prevented or ameliorated by caloric restriction commencing early in life

碩士
國立臺灣大學
醫學工程學研究所
107
Pleural empyema is an inflammatory condition characterized by pus accumulation inside pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause fibroblasts proliferation and deposition of extracellular matrix, which will finally lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through chest drainage tube are frequently used for fibrinolysis in empyema patients. However, urokinase treatment requires multiple instillation (2~3 times per day, for 4~8 days) and is easily flowed out from the chest drainage tube due to its high water solubility. In this in vitro study, we develop a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) and investigate into different combinations of P407 and HA for the optimal effect of urokinase loading and release. The micellization and gelation behavior, gel dissolution, drug release, gel microstructure and fourier transform infrared spectroscopy (FT-IR) of the P407-HA hydrogel are also studied. The addition of HA decrease the critical micellization temperature (CMT) without affecting the micellization intensity and critical gelation temperature (CGT). The P407-HA hydrogel also has better hydrogel property and a more compact microstructure comparing to the P407 alone. The thermo-responsive P407-HA hydrogel may have a promising potential in hydrophilic drugs loading and delivery.

碩士
國立臺灣大學
工程科學及海洋工程學研究所
107
Owing to the rapid development of the science and technology, computational modeling has become one of the most important ways to discover innovative materials. In this thesis, molecular dynamics is used to study physical properties such as glass transition temperature, Young’s modulus and mean square displacement of the materials. In part one, we aimed to remain low Tg and enhance the stiffness of the materials by discussing the physical properties of the polymer electrolytes. We found that as we modified the side chain of the polyethylene oxide, the volume of the functional groups influences the mobility of the polymer a lot and it also affects the physical properties indirectly. Judging from the results, polymer electrolytes materials which are added with fluoro functional groups has no change in glass transition temperature about 250K but has a lot improvement in Young’s modulus about 1.6GPa. The physical properties meet the goal that we aimed to modify. In part two, molecular dynamics is also used to describe the physical properties of the system. It is also found that as we increase the ratio of the water in the artificial corneal material system which is poloxamer 407, Young’s modulus decrease rapidly and the dramatic fluctuations in stress strain diagram because the H2O dominate the physical properties by molecular dynamics simulations. In conclusion, we can preliminary understanding and predict the physical properties of the materials by using molecular dynamics simulations.

Dissertação de mestrado integrado em Engenharia de Polímeros
O objetivo da presente dissertação consiste em desenvolver e avaliar o potencial de uma membrana biopolimérica de acetato de celulose (AC), contendo nanopartículas de prata (Ag-NPs) e/ou alumínio (Al-NPs) no tratamento e remediação de meios aquáticos. Para esse efeito, foram sintetizadas membranas de AC contendo Ag-NPs e/ou Al-NPs através do método de evaporação do solvente, obtendo-se Ag-NPs por redução química do nitrato de prata (AgNO3) com o agente redutor, borohidreto de sódio (NaBH4). As Al-NPs foram obtidas por síntese in situ de um precursor à base de alumínio, o isopropóxido de alumínio (Al(Pr-i-O)3) na presença de ácido clorídrico (HCl). Investigou-se ainda o efeito da estabilização das Ag-NPs através da incorporação de um surfactante, o poloxamer 407 (P407). As membranas de AC contendo Ag-NPs com e sem a presença do P407 foram caracterizadas através de ensaios de microscopia eletrónica de varrimento (SEM), espectroscopia dispersiva de raios-X (EDS), dispersão de luz dinâmica (DLS), espectroscopia de infravermelho por transformada de Fourier (FTIR), análise termogravimétrica (TGA), espectroscopia UV-Visível, análise dinâmico-mecânica (DMA) e medição de ângulos de contacto, assim como através de estudos da atividade antibacteriana. Como o principal objetivo desta dissertação consiste no desenvolvimento de uma membrana de nanocompósito para duas possíveis aplicações no tratamento de água contaminadas, inibir/remover microrganismos e o ião fosfato, foram realizados estudos da atividade antibacteriana, assim como estudos cinéticos de adsorção de fósforo. Da caracterização das membranas obtidas conclui-se que a incorporação de Ag-NPs na matriz de AC induziu uma melhoria das propriedades térmicas e mecânicas relativamente às de AC puro. Enquanto, a incorporação de P407 introduziu modificações superficiais na matriz de AC tornando-a mais hidrofílica. Resultados obtidos no estudo cinético de adsorção de fósforo nas membranas contendo Ag-NPs e Al-NPs confirmaram a eficiência destas membranas na remoção do fósforo. Relativamente ao carácter antibacteriano destas, este foi comprovado in situ, no qual se verificou o efeito bactericida nos testes realizados em águas com bactérias em suspensão.
The aim of this dissertation is to develop and evaluate the potential of a biopolymeric membrane of cellulose acetate (CA), containing silver nanoparticles (Ag-NPs) and/or aluminum nanoparticles (Al-NPs) for the treatment and remediation of aquatic environments. For this purpose, CA membranes containing Ag-NPs and/or Al-NPs were synthesized by solvent casting, resulting in Ag-NPs obtained by chemical reduction of silver nitrate (AgNO3) with the reducing agent, sodium borohydride (NaBH4). The Al-NPs were obtained by in situ synthesis of an aluminum-based precursor, aluminum isopropoxide (Al(Pr-i-O)3) in the presence of hydrochloric acid (HCl). The stabilization effect of Ag-NPs through the incorporation of a surfactant, poloxamer 407 (P407), was also investigated. The CA membranes containing Ag-NPs with and without the presence of P407 were characterized by scanning electron microscopy (SEM), dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), Fourier-transformed infrared spectroscopy (FTIR), thermogravimetry analysis (TGA), ultraviolet-visible absorption spectroscopy, dynamic mechanical analysis (DMA), and contact angle measurement, as well as antibacterial activity studies. Since the main objective of this dissertation is the development of a nanocomposite membrane for two possible applications for contaminated water treatment, able to inhibit/remove microorganisms and phosphate ion, antibacterial activity studies, as well as adsorption kinetics of phosphorus studies, were performed. The characterization of the obtained membranes show that the incorporation of Ag-NPs in the CA matrix induced an improvement of the thermal and mechanical properties of the pure CA. The incorporation of P407 introduced superficial changes in the CA matrix, making the membrane more hydrophilic. Results obtained from the adsorption kinetics of phosphorous studies confirmed the phosphorous removal effectiveness of the CA membranes containing Ag-NPs and Al-NPs. In situ CA membranes containing Ag-NPs and Al-NPs antimicrobial behavior was proved, which revealed the bactericidal effect in the performed tests against suspended bacteria in water.