Study of the improvement of cellulose processing in ionic liquid by using Carbon Dioxide

Se han revisado y analizado varios aspectos del procesado de celulosa en líquidos iónicos. Las ventajas y desventajas del uso de líquidos iónicos en la producción de derivados de celulosa se discutieron para la esterificación y eterificación de celulosa. El dióxido de carbono se presenta como un co-disolvente prometedor para el procesado de lignocelulosa en líquido iónico ya que es un gas inerte sin limitación ambiental que presenta altas solubilidades en líquidos iónicos incluso a bajas presiones, y se puede separar fácilmente de la mezcla por despresurización. El objetivo de este trabajo es estudiar cómo el CO2 puede mejorar diferentes aspectos del procesado de biomasa utilizando líquidos iónicos. Para lograr el objetivo de esta tesis varios aspectos se han tenido en cuenta: Efecto del CO2 en las propiedades de las mezclas CO2 + ILs (equilibrio de fases, puntos de fusión puntos, viscosidades y densidades); Análisis de la influencia de CO2 en procesos de reacción, específicamente en reacciones de sustitución con el fin de producir polímeros derivados de la celulosa, para ello la síntesis bien conocida de acetato de celulosa se elige como modelo de reacción; Estudiar la aplicación de CO2 en la recuperación de materiales valiosos derivados de la celulosa y para lograr este objetivo se obtiene la preparación de aerogeles de celulosa a partir de los líquidos iónicos mediante secado supercrítico.Departamento de Ingeniería Química y Tecnología del Medio AmbienteDoctorado en Ingeniería Química y Ambienta

A study of the transdermal drug diffusion properties of rooperol tetra-acetate

The rapidly growing interest in the potential use of topical drug delivery formulations has resulted in increased use of the skin as a vital port for drug delivery. Extensive research has been conducted in designing vehicles capable of delivering a desired amount of drug to a specific site, to produce the desired pharmacological response. Rooperol tetra-acetate is a lipophilic, cytotoxic drug with the potential for use in the treatment of solar keratosis. For effective pharmacological action, delivery of the drug to the epidermal/dermal junction of the skin is required. A study of the topical penetration properties of rooperol tetra-acetate from different topical bases, each possessing different physico-chemical properties, was performed. The assessment involved a comparison of the diffusion properties under occlusive and non occlusive conditions when the drug was formulated into a gel, Cetomacrogol Cream B.P. (oil-inwater), Simple Ointment B.P. and an extemporaneously prepared water-in-oil topical cream. The in vitro experiments were conducted using polydimethylsiloxane and rat membrane mounted in a Franz diffusion cell. The topical permeation kinetics of rooperol tetra-acetate were determined by exploring the release characteristics of the active ingredient from the vehicles formulated and the permeability properties of the drug through the membranes employed. Further studies involved investigating the utilization of supersaturated systems intended to increase the thermodynamic activity of the drug when formulated into a propylene glycol/water vehicle (with and without polymer). To measure the release of rooperol tetra-acetate into the skin from a topical base it was necessary to, firstly, develop a suitable quantitative method for the analysis of the active drug in the aqueous receptor phase of in vitro diffusion cells. The second stage of product development was the design of an effective delivery system to facilitate the release of the diffusant from its base. A high performance liquid chromatographic method was utilized for the identification and quantification of the active drug. As validation is an important aspect in the development and subsequent utilization of an analytical procedure, the developed HPLC technique was validated by determining the precision, accuracy, range, limit of quantitation and sensitivity of the system. Lastly, the stability of rooperol tetra-acetate at elevated temperatures was assessed and a stability profile of the drug was generated for the three-month period of analysis. The results obtained following chromatographic analysis of the receptor phase sampled during the diffusion experiments indicate that the gel and oil-in-water formulations most effectively promoted the diffusion of rooperol tetra-acetate across polydimethylsiloxane membrane. The water-in-oil system exhibited lower flux rates and the ointment showed the least drug release. Occlusion of the topical vehicle increased the diffusitivity of the permeant from all formulations analysed. The permeation assessment results of the supersaturated systems showed enhanced diffusion of rooperol tetra-acetate across polydimethylsiloxane and rat membrane. The high thermodynamic activity existing in supersaturated systems most effectively increased the driving force for drug diffusion resulting in enhanced percutaneous penetration of rooperol tetra-acetate beyond the release and transport limitations of saturated solutions. These results provide the basis on which an effective topical drug delivery vehicle may be designed for this new drug entity

Applications of Small Heterocycles: Oxetanes as Additives and Cosolvents and Oxazolines as Linkers for Controlled Release from Silica Nanoparticles

In the first chapter of this dissertation, the design and synthesis of bifunctional additives and cosolvents containing an oxetane moiety are described. The use of dimeric oxetanes as additives for reactions involving organometallic agents—namely, organolithium, organozirconium, and organomagnesium reagents was studied. A dimeric bisoxetanyl ether showed promise for solvating organolithium aggregates, but dimeric oxetanyl ethers were not useful additives in hydrozirconation reactions. A bisoxetanyl sulfide is being investigated further as an additive for Grignard reactions. A bisoxetanyl sulfoxide (MMS350) was developed as a dimethylsulfoxide substitute that showed utility for enhancing the aqueous solubility of small organic molecules. In the second chapter, efforts toward the development of agents for protection and mitigation of ionizing radiation damage are outlined. It was discovered that administration of MMS350 prolonged survival in irradiated mice. Moreover, mice given MMS350 in their drinking water had lower incidences of pulmonary fibrosis. Additional analogs of MMS350 were synthesized for further investigation of the molecular and structural requirements for successful sulfoxide-containing radiation protectors. In the third chapter, the design and proof-of-concept study of using an oxazoline linker for functionalization and pH-dependent release of reactive oxygen species (ROS) scavengers from silica nanoparticles is discussed. pH-Dependent hydrolysis of model oxazolines was achieved by modulating the substitution on the oxazoline moiety. Moreover, functionalized silica nanoparticles were successfully endocytosed by macrophages. Our studies have laid the groundwork for the design of covalently modified nanoparticles for delivery of ROS