Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xxii, 220 p.; also includes graphics (some col.). Includes bibliographical references (p. 202-220). Available online via OhioLINK's ETD Center.

Chronic diseases can often be managed by constantly delivering therapeutic amounts of drug for prolonged periods. A controlled release for extended duration would replace the need for multiple and frequent dosing. Local drug release would provide added benefit as a lower dose of drug at the target site will be needed as opposed to higher doses required by whole body administration. This would provide maximum efficacy with minimum side effects. Nonetheless, a problem with the known implantable drug delivery devices is that the delivery rate cannot be controlled, which leads to drug being released in an unpredictable pattern resulting in poor therapeutic management of patients. This dissertation is the result of development of an implantable drug delivery system that is capable of long-term zero order local release of drugs. The device can be optimized to deliver any pharmaceutical agent for any time period up to several years maintaining a controlled and desired rate. Initially significant efforts were dedicated to the characterization, biocompatibility, and loading capacity of nanoporous metal surfaces for controlled release of drugs. The physical characterization of the nanoporous wafers using Scanning electron microscropy (SEM) and atomic force microscopy techniques (AFM) yielded 3.55 x 10⁴ nm³ of pore volume / μm² of wafer surface. In vitro drug release study using 2 - octyl cyanoacrylate and methyl orange as the polymer-drug matrix was conducted and after 7 days, 88.1 ± 5.0 % drug was released. However, the initial goal to achieve zero order drug release rates for long periods of time was not achieved. The search for a better delivery system led to the design of a perforated microtube. The delivery system was designed and appropriate dimensions for the device size and hole size were estimated. Polyimide microtubes in different sizes (125-1000 μm) were used. Micro holes with dimensions ranging from 20-600 μm were fabricated on these tubes using photolithography, laser drilling, or manual drilling procedures. Small molecules such as crystal violet, prednisolone, and ethinyl estradiol were successfully loaded inside the tubes in powder or solution using manual filling or capillary filling methods. A drug loading of 0.05 – 5.40 mg was achieved depending on the tube size and the drug filling method used. The delivery system in different dimensions was characterized by performing in vitro release studies in phosphate buffered saline (pH 7.1-7.4) and in vitreous humor from the rabbit’s eye at 37.0 ± 1.0°C for up to four weeks. The number of holes was varied between 1 and 3. The tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE). Linear release rates with R²>0.9900 were obtained for all groups with CV and EE. Release rates of 7.8±2.5, 16.2±5.5, and 22.5±6.0 ng/day for CV and 30.1±5.8 ng/day for EE were obtained for small tubes (30 μm hole diameter; 125 μm tube diameter). For large tubes (362-542 μm hole diameter; 1000 μm tube diameter), a release rate of 10.8±4.1, 15.8±4.8 and 22.1±6.7 μg/day was observed in vitro in PBS and a release rate of 5.8±1.8 μg/day was observed ex vivo in vitreous humor. The delivery system was also evaluated for its ability to produce a biologically significant amounts in cells stably transfected with an estrogen receptor/luciferase construct (T47D-KBluc cells). These cells are engineered to produce a constant luminescent signal in proportion to drug exposure. The average luminescence of 1144.8±153.8 and 1219.9±127.7 RLU/day, (RLU = Relative Luminescence Units), yet again indicating the capability of the device for long-term zero order release. The polyimide device was characterized for biocompatibility. An automated goniometer was used to determine the contact angle for the device, which was found to be 63.7±3.7degreees indicating that it is hydrophilic and favors cell attachment. In addition, after 72 h incubation with mammalian cells (RAW 267.4), a high cell distribution was observed on the device’s surface. The polyimide tubes were also investigated for any signs of inflammation using inflammatory markers, TNF-α and IL-1β. No significant levels of either TNF-α or IL-1β were detected in polyimide device. The results indicated that polyimide tubes were biocompatible and did not produce an inflammatory response. / text

Orientador: Claudio Airoldi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-21T09:21:18Z (GMT). No. of bitstreams: 1 Vieira_AdrianaPires_D.pdf: 2625082 bytes, checksum: 5ad150ad19ef89615a506cf16abb5e3b (MD5) Previous issue date: 2012 / Resumo: O biopolímero quitosana foi modificado quimicamente a fim de se potencializar suas propriedades. Duas sequências de reações foram realizadas: i) imobilização do metil acrilato seguido da cisteamina, obtendo-se os materiais QMA e QMAC, e ii) imobilização envolvendo o etilenossulfeto, acrilato de metila e cisteamina, obtendo-se os materiais, QE, QEMA e QEMAC. As estruturas correspondentes foram caracterizadas por análise elementar, espectroscopia na região do infravermelho, ressonância magnética nuclear no estado sólido C, termogravimetria, difração de raios X e microscopia eletrônica de varredura. Os novos biopolímeros foram testados para a aplicação em sorção dos cátions de chumbo e cádmio e também do corante aniônico azul reativo e do catiônico verde brilhante. Também foram aplicados para a imobilização e liberação controlada do fármaco ibuprofeno. Os novos biopolímeros obtidos mostraram-se bons sorventes frente aos cátions metálicos e ao corante aniônico. No estudo de cinética de sorção foram utilizadas as equações de pseudo primeira e segunda ordens a fim de verificar o mecanismo que envolve o processo, sendo que o de segunda ordem mostrou-se o mais adequado. Nos experimentos isotérmicos foram utilizadas as equações de Langmuir e Freundlich, onde o modelo de Langmuir foi o que apresentou melhor ajuste. Os materiais também foram utilizados para imobilização e liberação controlada do fármaco, na forma de pastilhas e filmes reticulados com glutaraldeído. Os experimentos mostraram que a liberação é sensível ao pH. As quitosanas quimicamente modificadas permitiram a redução da liberação do fármaco no fluido gástrico, uma vez que os grupos funcionais presentes causam uma diminuição na taxa de intumescimento a pH 1,2, em contraste com o comportamento ocorrido em pH 7,4 que simula o fluido intestinal, onde há um aumento na taxa de intumescimento. Em tais condições a carga negativa do ibuprofeno é eletrostaticamente repelida pela superfície negativa dos derivados da quitosana / Abstract: The chitosan biopolymer is chemically modified in order to enhance its properties.Two sequences of reactions were carried out: i) immobilization of methyl acrylate followed by cysteamine to yield materials QMA and QMAC, and ii) immobilization ethylene sulfide, methyl acrylate and cysteamine to yield materials QE, QEMA, QEMAC. The corresponding structures were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance in solid state C NMR, thermogravimetry, X-ray diffraction and scanning electron microscopy. The new polymers were tested for use in sorption of cations of lead and cadmium and also reactive blue dye anionic and cationic bright green. Were also applied to the immobilization and controlled release of drugs using ibuprofen as a model drug. The new polymers obtained proved to be good sorbents for the metallic cations and the anionic dye. In the sorption kinetics study were used equations first and second pseudo order to verify the mechanism that involves the process, and the second order proved to be the most appropriate. In isothermal experiments were used Langmuir and Freundlich equations, where the Langmuir model showed the best fit. The materials were also used for immobilization and controlled release of the drug in the form of tablets and film crosslinked with glutaraldehyde. The experiments show that the release is pH sensitive. The chemically modified chitosans possible to reduce the release of the drug in the gastric fluid, because functional groups present cause a decrease in swelling rate at pH 1.2. In contrast to the behavior that occurred at pH 7.4 simulated intestinal fluid, where there is an increase in the rate of swelling. Under such conditions the negative charge of ibuprofen is repelled electrostatically by the negative surface of the derivatives of chitosan / Doutorado / Quimica Inorganica / Doutora em Ciências

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Os alquilglicosÃdeos constituem uma nova e interessante classe de surfactantes por serem biodegradÃveis, atÃxicos e sintetizados a partir de fontes renovÃveis e abundantes na natureza. Estas propriedades os tornam potencialmente mais apropriados que outros surfactantes os quais prejudicam o meio ambiente. O presente trabalho trata da sÃntese e caracterizaÃÃo de duas sÃries de alquilglicosÃdeos utilizando os Ãlcoois C10, C16 e C18 como parte hidrofÃbica e glicose e derivados da degradaÃÃo da amilose como partes hidrofÃlicas. A sÃntese dos alquilglicosÃdeos foi realizada atravÃs da reaÃÃo usual de KÃenig-Knorr com algumas modificaÃÃes. A caracterizaÃÃo estrutural dos surfactantes foi acompanhada por ressonÃncia magnÃtica nuclear 1H, 13C (RMN) juntamente com a espectroscopia de absorÃÃo na regiÃo do infravermelho (IV). Os estudos de RMN e IV permitiram caracterizar detalhadamente as junÃÃes entre os grupos hidrofÃlicos e hidrofÃbicos, como predominantemente glicosÃdica. A cromatografia de permeaÃÃo de gel (GPC) mostrou evidÃncias da formaÃÃo dos surfactantes com aproximadamente cinco anÃis glicosÃdicos ligados à cadeia alquÃlica. Estruturas de cristais lÃquidos, identificadas pela presenÃa de pontos de fusÃo duplos, foram observadas atravÃs da tÃcnica de calorimetria exploratÃria diferencial (DSC), revelando as propriedades termotrÃpicas dos surfactantes. O mÃtodo de du NoÃy foi utilizado para determinar a tensÃo superficial e concentraÃÃo micelar crÃtica (cmc) das soluÃÃes aquosas Ãs vÃrias concentraÃÃes. Observou-se que para as duas sÃries de surfactantes, o aumento do comprimento da cadeia alquÃlica levou à reduÃÃo esperada da cmc. As energias envolvidas nos processos de adsorÃÃo e micelizaÃÃo calculadas a partir das isotermas de tensÃo superficial de equilÃbrio versus ln da concentraÃÃo indicam a cooperatividade dos grupos hidrofÃlicos e hidrofÃbicos nestes processos. / Alkyl glucosides constitute a new and interesting class of surfactants, as they are biodegradable, nontoxic, and synthesized from renewable resources. These properties make them substitutes for other surfactants which are potentially damaging to the environment. The present work deals with the synthesis and characterization of two series of alkyl glucosides, which used C10, C16 and C18 alcohols as the hydrophobic part and glucose and glucose residues derived from degradation of amylose (which was essentially free from amilopectin) as hydrophilics parts. The alkyl glucosides synthesis was performed by the usual KÃenigs-Knorr reaction with some modifications. The molecular structures of the surfactants were characterized by 1H, 13C nuclear magnetic resonance (NMR) together with infra-red (IR) spectroscopy. The study by NMR and IR allowed the junctions between hydrophilic head-groups and hydrophobic tailgroups to be characterized predominantly as -glycosidic. Gel permeation chromatography (GPC) showed evidences of the formation of the surfactants with five glucosides rings linked to the alkyl chain. Liquid crystals structures were investigated by the differential scanning calorimetry (DSC) technique confirming the characteristics of thermotropics properties, through the presence of double melting points. The du NoÃy method was used to determine the surface-tension and critical micelle concentration (cmc) of aqueous solutions at various concentrations. For the two series of surfactants, it was observed that the increase of the alkyl chain caused the already expected decrease of cmc. The energies involved in the adsorption and micellization process calculated from the equilibrium surface tension isotherm versus ln concentration indicates co-operativety from the hydrophilics and hydrophobics grups.

Disponibiliza??o em conte?do parcial do trabalho, conforme Termo de Autoriza??o. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-02-14T19:00:46Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-03-06T12:24:50Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Made available in DSpace on 2017-03-06T12:24:50Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) Previous issue date: 2016 / Na ind?stria farmac?utica, os pol?meros s?o capazes de desempenhar a fun??o de matriz para libera??o controlada de f?rmacos. Isto tem como vantagem a minimiza??o dos efeitos adversos dos medicamentos e a otimiza??o do tratamento. Entre os pol?meros utilizados para tal finalidade, tem-se o poli(3-hidroxibutirato) (PHB) conhecido por sua origem natural, um material que se degrada a produtos n?o t?xicos para o organismo, o que garante o seu emprego como biomaterial. Quando utilizado em associa??o a outros pol?meros, s?o denominados Blendas, essas misturas modificam as caracter?sticas f?sico-qu?micas dos pol?meros para serem empregados em finalidades diversas. Desta forma este trabalho teve como objetivo o desenvolvimento de uma matriz polim?rica capaz de ser utilizada para libera??o controlada de f?rmacos. Para tal, foram produzidas duas membranas diferentes uma de PHB e outra de Blenda Poli (3-hidroxibutirato)/Polipropilenoglicol, PHB/PPG (90:10), com concentra??es diferentes de f?rmaco, contendo 5% e 25% em massa. O f?rmaco modelo foi a Sinvastatina. Estes dispositivos foram produzidos por dissolu??o seguida de evapora??o do solvente, formando filmes de 0,5 mm de di?metro que foram analisados quanto a sua degrada??o in vitro e in vivo, em implantes subcut?neos. Os materiais foram analisados utilizando espectroscopia na regi?o do infravermelho, termogravimetria, microscopia eletr?nica de varredura e por testes histol?gicos. Os filmes ? base de PHB, apresentaram degrada??o in vitro e in vivo mais lenta quando comparados ?s blendas, no entanto em ambos os casos, os materiais que continham maior percentual de Sinvastatina apresentaram maior degrada??o e libera??o do f?rmaco. As l?minas histol?gicas revelam a presen?a do tecido em torno dos dispositivos e aus?ncia de inflama??o o que comprova a biocompatibilidade dos materiais estudados. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2016. / In the pharmaceutical industry, the polymers are able to drive the controlled release of drugs. Its brings the advantage of minimizing adverse effects of medicines and optimization of treatment. Among the polymers used for this purpose the poly (3-hydroxybutyrate) has known for their natural origin, its degradation to non-toxic effects to the life tissue which ensures their use as subcutaneous implants. A blend is a mixture of different polymers, these mixtures are able to modify the physicochemical characteristics of the polymers for several uses. This study aimed to develop a polymer matrix can be used as a way for controlled release of drugs. For this purpose, two different membranes were produced, the PHB and a Poly(3-hydroxybutyrate)/Polypropylene glycol blends, PHB/PPG (90:10), with different concentrations of drug with 5% and another 25%. The simvastatin was chosen as a model. These devices were manufactured by casting to form films of 0.5 mm diameter that were analyzed for in vitro and in vivo degradation tests using subcutaneous implants. The materials were analyzed using infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and histological tests. The films based on PHB presented a slower degradation in vitro and in vivo degradation tests when compared to the blends, however in both cases those materials containing a higher percentage of simvastatin has shown the higher degradation and release of the drug. The histological sections showed a tissue colonization and absence of inflammation which demonstrates the biocompatibility of the implants.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-05T19:05:37Z No. of bitstreams: 1 IMARALLY VITOR DE SOUZA RIBEIRO NASCIMENTO - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2760797 bytes, checksum: 7ecba4dc55afbb264d93e04510c69d66 (MD5) / Made available in DSpace on 2018-04-05T19:05:37Z (GMT). No. of bitstreams: 1 IMARALLY VITOR DE SOUZA RIBEIRO NASCIMENTO - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2760797 bytes, checksum: 7ecba4dc55afbb264d93e04510c69d66 (MD5) Previous issue date: 2014-08-29 / Capes / Os sistemas de liberação controlada de fármacos oferecem inúmeras vantagens quando comparados a outros de dosagem convencional tendo os polissacarídeos biodegradáveis ganhando bastante aceitação no desenvolvimento desses sistemas. A quitosana é um exemplo de polissacarídeo biodegradáveis, cuja taxa de liberação pode ser modulada a partir da reticulação iônica com o Tripolifosfato de sódio (TPP). A piperina é um dos principais constituintes da pimenta negra, possuindo diversas ações farmacológicas que podem causar a morte de células cancerígenas e quando conjugada com a quitosana apresenta melhor biodisponibilidade e ação mais rápida. Sendo assim, esse trabalho objetivou desenvolver e avaliar comparativamente membranas poliméricas de quitosana e quitosana reticulada pelo TPP para uso em sistema de liberação controlada de piperina, com a finalidade de obter uma via alternativa para a administração desse fármaco. A piperina foi adicionada sob agitação constante à solução de quitosana e as membranas foram obtidas pelo método de evaporação do solvente. As membranas desenvolvidas foram caracterizadas pelas técnicas de Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR), Difração de Raios X (DRX), Microscopia Ótica (MO), Microscopia Eletrônica de Varredura (MEV), Espectroscopia por Energia Dispersiva de Raios X (EDS), Análise Termogravimétrica (TG), Análise de Calorimetria Exploratória Diferencia (DSC), Eficiência de Carregamento (EC) através da Cromatografia Liquida de Ultra Eficiência (CLUE), Avaliação da Viabilidade Celular dos Macrófagos (MTT). Observou-se na análise por FTIR bandas características da quitosana, do agente reticulante e da piperina, como também bandas que caracterizam uma interação entre a quitosana e a piperina. A técnica de DRX demonstrou alteração no caráter semicristalino da quitosana com a presença da piperina e do tripolifosfato. Foi possível perceber, através das técnicas de MO e MEV, alteração na morfologia da membrana contendo piperina quando comparada a de quitosana pura, com a presença de partículas fibrilares. As análises de TG e DSC evidenciaram que quando a piperina foi adicionada à quitosana esta proporcionou uma maior estabilidade térmica ao sistema. O ensaio eficiência de carregamento evidenciou que a extração do o fármaco foi eficaz e que a reticulação influenciou na extração deste. As membranas desenvolvidas apresentaram potencial citotóxico para as células de câncer mamário humano MCF 7. Nas condições desenvolvidas nesta pesquisa o sistema indicado como referência para ensaios de liberação e novos ensaios biológicos é o sistema MQPR. Diante do exposto o sistema desenvolvido apresenta-se como promissor para a obtenção de um sistema para liberação controlada de fármacos. / Controlled drug delivery systems offer many advantages when compared to other conventional dosage methods with biodegradable polysaccharides gaining enough acceptance in the development of these systems. Chitosan is an example of a biodegradable polysaccharide, whose rate of release can be modulated from the ionic crosslinking with sodium tripolyphosphate (TPP). Piperine is one of the major constituent of black pepper, having many pharmacological actions that can cause the death of cancer cells and when combined with chitosan has better bioavailability and faster action. Therefore, this study aimed to develop and comparatively evaluate polymer membranes of chitosan and crosslinked chitosan by TPP to be used in a controlled release system of piperine, in order to obtain an alternative route for the administration of this drug system. Piperine was added under constant stirring to the solution of chitosan and membranes were obtained by the solvent evaporation method. The developed membranes were characterized by the techniques of Infrared Spectroscopy in the Region Fourier Transform (FTIR), X-ray Diffraction (XRD), Optical Microscopy (OM), scanning electron microscopy (SEM), Energy Dispersive Spectroscopy X-Ray (EDS), Thermogravimetric Analysis (TGA), Scanning Calorimetry Analysis of Difference (DSC), Efficiency Charge (EC) by liquid Chromatography Ultra Efficiency (HPLC), Assessment of Cell Viability of Macrophages (MTT). It was observed by FTIR analysis, bands characteristic of chitosan, the crosslinking agent and piperine, as well as bands characterizing an interaction between chitosan and piperine. The XRD technique showed change in semi-crystalline nature of chitosan in the presence of piperine and tripolyphosphate. It was possible to see, through the techniques of OM and SEM, changes in the morphology of the membrane containing piperine compared to pure chitosan, with the presence of fibrillar particles. TG analysis showed that, when piperine was added to the chitosan it provided a smaller weight loss of the system, showing the interaction between chitosan and piperine. DSC analysis showed that addition of piperine into chitosan provided greater stability to the system. The charging efficiency test showed that the drug can be entrapped by 57% in the uncrosslinked membranes and crosslinking influenced the extraction of drug. The developed membranes showed cytotoxic potential for human breast cancer cells MCF 7. Under the developed conditions in this research, MQPR system was shown as a reference for drug delivery testing and new biological tests. Given the above, the developed system is presented as promising for obtaining a system for controlled release of drugs.

Submitted by ANA KARLA PEREIRA RODRIGUES (anakarla_@hotmail.com) on 2017-08-02T15:41:08Z No. of bitstreams: 1 arquivototal.pdf: 5765942 bytes, checksum: 274481954c5d791369e586a0fa87060c (MD5) / Made available in DSpace on 2017-08-02T15:41:08Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 5765942 bytes, checksum: 274481954c5d791369e586a0fa87060c (MD5) Previous issue date: 2016-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Polymer blends are a prompt and economical way to obtain new materials and have attracted considerable interest. Xanthan gum (GX) and poly (vinyl alcohol) (PVA) are polymers of great interest because of their properties. The high hydrophilic nature of these materials limits their applications, so they need to be submitted to the crosslinking process. In this work were prepared and characterized polymeric films (1% w / v) consisting of xanthan gum and poly (vinyl alcohol) without crosslinking agent and crosslinked with citric acid (CA) by casting for use in controlled drug release. The infrared analysis demonstrated possible interactions between the polymers in the blend and the incorporation of crosslinker into the polymer matrix. The scanning electron microscope revealed that the surfaces of the films are smooth and homogeneous even with the addition of crosslinking agent. The solubility, swelling and permeability to water vapor tests showed synergism between properties of polymers in the blend and citric acid attributed to the film water resistance. The compositions are stable in an inert atmosphere (N2), and films crosslinked with citric acid exhibited better thermal stability when compared with no crosslinking. The thermal degradation kinetics study complemented the results of thermal analysis showing that the PVA films are more stable and the crosslinking agent has improved thermal properties of the films. Biodegradability tests in soil revealed greater degradation to the polymer blends over a period of 160 days. The films exhibited no antimicrobial activity against the microorganisms studied. The application of crosslinked films with citric acid on controlled drug release showed that acetaminophen, propranolol and fluconazole release mechanism was controlled primarily by diffusion, swelling and relaxation of the polymer chains, with constant release profiles for 24 h, demonstrating that the developed films are promising materials for controlled drug release. / Blendas poliméricas representam uma forma rápida e econômica para obtenção de novos materiais e vêm atraindo bastante atenção. A goma xantana (GX) e o poli (álcool vinílico) (PVA) são polímeros de interesse devido as suas propriedades. O alto caráter hidrofílico desses materiais limitam suas aplicações, por isso eles precisam passar pelo processo de reticulação. Neste trabalho foram preparados e caracterizados filmes poliméricos (1% m/v) constituídos por goma xantana e poli (álcool vinílico) sem agente reticulante e reticulados com ácido cítrico (AC) pelo método da evaporação do solvente para aplicação na área de liberação controlada de fármacos. Os dados de espectroscopia de infravermelho sugeriram possíveis interações entre os polímeros na blenda e a incorporação do reticulante na matriz polimérica. A microscopia eletrônica de varredura revelou que as superfícies dos filmes são lisas e homogêneas, mesmo com a adição do agente reticulante. Os ensaios de solubilidade, intumescimento e permeabilidade ao vapor de água mostraram o sinergismo das propriedades dos polímeros na blenda e que o ácido cítrico atribuiu aos filmes resistência à água. As composições mostraram-se estáveis em atmosfera inerte (N2), e os filmes reticulados com ácido cítrico exibiram melhor estabilidade térmica quando comparados com os sem reticulante. O estudo de cinética de degradação térmica complementou os resultados de análise térmica mostrando que os filmes de poli (álcool vinílico) são mais estáveis e que o agente reticulante aumentou as propriedades térmicas dos filmes. Os ensaios de biodegradabilidade em solo mostraram maior degradação para as blendas poliméricas em um período de 160 dias. Os filmes não demonstraram atividade antimicrobiana frente aos microrganismos estudados. A aplicação dos filmes reticulados com ácido cítrico na área de liberação controlada mostrou que o mecanismo de liberação de paracetamol, propranolol e fluconazol foi controlado principalmente por difusão, intumescimento e relaxamento das cadeias poliméricas, apresentando perfis de liberação constantes em 24 h, demonstrando que os filmes desenvolvidos são materiais promissores para liberação controlada de fármacos.