Ivonete B. Araújo

Xylan from corn cobs, a promising polymer for drug delivery: Production and characterization

Although many authors have reported several beneficial effects ascribed to xylan, such as inhibitory action on mutagenicity activity, antiphlogistic effects, and mitogenic and comitogenic activities, few papers have investigated a systematic study on the technological properties of this polymer. The aim of the present work was to evaluate xylan as a promise raw material for the pharmaceutical industry. The water-insoluble xylan samples were extracted from corn cobs following several steps. The obtained powered sample was analyzed by infrared and RMN spectroscopy, and characterized regarding their particle size, bulk and tap densities, compressibility index, compactability, Hausner ratio, and angle of repose. According to the results, infrared and RMN spectroscopy were shown to be able to evaluate the xylan structural conformation and composition, respectively. In addition, rheological data demonstrated that xylan powder obtained from corn cobs may be characterized as a material with low density and very cohesive flow properties.

Influence of the Lipophilic External Phase Composition on the Preparation and Characterization of Xylan Microcapsules—A Technical Note

Scientific studies on new drug delivery systems have significantly increased in the past few years and this growth is expected to continue in the near future (1). Such systems are of great interest because of their ability to improve drug performance in terms of efficacy, safety, and patient compliance (1). In many cases, conventional drug delivery provides an increase of drug concentration at potentially toxic levels (2). Additionally, the need for delivering drugs with fewer side effects has prompted the development of new drug delivery systems (1). Xylan is the second most abundant polymer found in hardwoods and annual plants (3), particularly in agricultural residues such as grain hulls, corn cobs, and corn stalks (4). Depending on the botanical source, the backbone chemical structure may vary. However, the majority of xylans present side chains of different sugars such as 4-O-methyl-d-glucoronic acid, O-acetyl-l-arabinose, l-arabinose, and d-glucoronic acid bond by a glycosidic linkage to the backbone (3). Because of its complex structure, the complete degradation of xylan requires the activity of several enzymes which are specifically produced by human colonic microflora (5). Therefore, xylan microcapsules may represent a novel and promising colon-specific drug delivery system. Microcapsules based on natural polymers may be produced by means of a variety of methods. Emulsion solvent extraction, emulsion solvent evaporation and interfacial cross-linking polymerization are the most commonly employed processes for the production of microcapsules (4). One of the critical parameters in the microencapsulation process is the external phase used in the emulsification step (6). In fact, the external phase can influence the microcapsules morphology, their aggregation state, and mainly the release of the microencapsulated active compound (7). Because the production of xylan-based microcapsules is a subject barely studied by scientists worldwide, the aim of this work was to evaluate the influence of the lipophilic external phase composition on the production and mean particle size of xylan microcapsules produced by interfacial cross-linking polymerization.

how can micelle systems be rebuilt by a heating process

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were then diluted at four different concentrations (50 mg · L−1, 5 mg · L−1, 0.5 mg · L−1, and 0.05 mg · L−1) to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC) from human donors and Candida parapsilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival rate from Cp. The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg · L−1). For K+ leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp (P < 0.05). AmB-DOC-H and AmB-DOC also revealed a similar profile of activity against Cp with an equivalent survival rate. In short, AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as AmB-DOC against fungal cells. The results highlight the importance of this new procedure as a simple, inexpensive, and safe way to produce a new kind of micelle system for the treatment of systemic fungal infections.

Prospective study for the development of emulsion systems containing natural oil products

Copaiba oil, when used as anti-inflammatory and anti-infective agent, presents two major problems: i) low absorption and bioavailability and ii) an unpleasant taste. Once an appropriate emulsion was achieved, the samples were prepared using different surfactant binary mixtures to obtain a range of HLB values between 4.5 and 16.5. The HLB value of copaiba oil was 14.8; this system has been stable for more than one year, and the pseudo-ternary diagrams were useful to describe the component proportions. These results indicated that the copaiba oil emulsion might be a promising vehicle for topical delivery of drugs and active cosmetic ingredients.

Development of superparamagnetic microparticles for biotechnological purposes.

Aqueous suspensions containing magnetic microparticles have been increasingly used in biosciences and biotechnology. This work describes an experimental procedure to produce superparamagnetic microparticles. The particles were prepared based on the coprecipitation of iron salts in alkaline medium. Afterwards, characterization was performed. Characterization data demonstrated that magnetite was the dominant phase in the analyzed sample, and 50% of them were in the size range of 0.5–5μm. The results suggest that the experimental protocol provided a simple synthesis route to produce superparamagnetic microparticles. Such properties may be very useful for biotechnological purposes.

Decrease in Fungizone™ Toxicity Induced by the Use of Lipofundin™ As a Dilutent: An In Vitro Study

The aim of this work was to develop an in vitro experimental protocol for the evaluation of toxicity and efficacy of an amphotericin B (AmB) micelle system, Fungizone, which was previously diluted with a lipid based emulsion for parenteral use, named Lipofundin LCT/MCT-20%. Two cell models were used for the experiments: Red Blood Cells (RBC) from human donnors and Candida tropicalis (Ct). These models were used to perform the toxicity and activity of the Fungizone/ Lipofundin admixture (AmB-LP) and the Fungizone (AmB-M) alone. While potassium (K+) and hemoglobin leakage from RBC were the parameters used to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-LP and AmB-M were assessed by K+ leakage or cell survival rate (CSR) from Ct. The results show that the toxicity of AmB-LP to RBC was concentration dependent concerning the K+ leakage; while at high concentrations, 5 and 50 mg x mL(-1), the leakage was 50.91 +/- 2.09% and 95.71 +/- 0.64%, respectively, at a concentration of 0.5 mg x mL(-1) this value was 17.16 +/- 1.57% and the value tended to zero for the lowest concentration studied, 0.05 mg x mL(-1). Surprisingly, AmB-LP induced very low hemoglobin leakage for all concentrations studied. At the highest concentration, 50 mg x mL(-1), this value was around 3%. When the cell model was Ct, the results changed completely. Not only high concentrations of AmB-LP, but also lower ones were able to induce a K+ permeability of around 100%. The CSR parameter showed an inverse correlation with the concentration; high values, between 50 and 5 mg x mL(-1), resulted in a CSR of around 8%. On the other hand, for lower concentration values, 0.05 and 0.5 mg x mL(-1), this one was around 80%. The same profile of activity against Ct was found for AmB-M. Only a small variation was found for the K+ leakage at 0.05 mg x mL(-1) that presented a value of 96.99 +/- 2.53%. However, AmB-M seemed to be much more toxic than AmB-LP. Its induction of hemoglobin leakage started at 0.5 mg x mL(-1) and reached the 100% at 5 mg x mL(-1). K+ leakage results were worse. The intermediate concentrations of study, 0.5 and 5 mg x mL(-1), presented a significant increase compared to AmB-LP. All together these results reveal that the activity of AmB is not only concentration dependent, but also depends on the drug carrier in which this compound was inserted. The AmB-LP preparation showed the same efficacy as AmB-M, but with a low toxicity. Therefore, AmB-LP presented a higher therapeutic index that permits the administration of high concentration of AmB without revealing side effects. However, the simple mixture of two complex pharmaceutical entities, as micelles and emulsions, should be analyzed carefully to assure that physicochemical stability is not reduced and thereby cause a different biodistribution in vivo.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

PURPOSE Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon (AmB-D) and two new different AmB formulations. METHODS three products were studied: Fungizon, and two Fungizon /Lipofundin admixtures, which were diluted through two methods: in the first one, Fungizon was previously diluted with water for injection and then, in Lipofundin (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05 mg x L(-1)). RESULTS The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg x L(-1), although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. CONCLUSION The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.

Analgesic efficacy of lidocaine and multimodal analgesia for chest tube removal: A randomized trial study

Objetivo: evaluar la eficacia analgesica de la lidocaina subcutanea y la analgesia multimodal para la remocion del tubo toracico despues de la cirugia cardiaca. Metodos: sesenta voluntarios fueron asignados aleatoriamente en dos grupos; 30 participantes en el grupo experimental recibieron lidocaina subcutanea al 1%, y 30 controlos recibieron un regimen de analgesia multimodal que comprende agentes antiinflamatorios sistemicos y opioides. La intensidad y calidad del dolor y rasgo y estado de ansiedad se evaluaron. La asociacion entre las variables independientes y el resultado final han sido evaluados por medio de la prueba de Chi-cuadrado con correccion de Yates y la prueba exacta de Fisher. Resultados: los grupos no mostraron diferencias significativas con respecto a la intensidad del dolor despues de la retirada del tubo toracico (p= 0,47). Los descriptores de dolor mas frecuentes informados por los participantes fueron apretado, agudo, punzante, ardiente e insoportable. Conclusion: el presente estudio sugiere que el efecto analgesico de la administracion subcutanea de lidocaina al 1% combinada con la analgesia multimodal es eficaz.

Eficacia analgésica de la lidocaína y la analgesia multimodal para la remoción del tubo torácico: Un estudio con ensayo aleatorio

Objetivo: evaluar la eficacia analgesica de la lidocaina subcutanea y la analgesia multimodal para la remocion del tubo toracico despues de la cirugia cardiaca. Metodos: sesenta voluntarios fueron asignados aleatoriamente en dos grupos; 30 participantes en el grupo experimental recibieron lidocaina subcutanea al 1%, y 30 controlos recibieron un regimen de analgesia multimodal que comprende agentes antiinflamatorios sistemicos y opioides. La intensidad y calidad del dolor y rasgo y estado de ansiedad se evaluaron. La asociacion entre las variables independientes y el resultado final han sido evaluados por medio de la prueba de Chi-cuadrado con correccion de Yates y la prueba exacta de Fisher. Resultados: los grupos no mostraron diferencias significativas con respecto a la intensidad del dolor despues de la retirada del tubo toracico (p= 0,47). Los descriptores de dolor mas frecuentes informados por los participantes fueron apretado, agudo, punzante, ardiente e insoportable. Conclusion: el presente estudio sugiere que el efecto analgesico de la administracion subcutanea de lidocaina al 1% combinada con la analgesia multimodal es eficaz.

Eficácia analgésica da lidocaína e analgesia multimodal na remoção do dreno torácico: Um estudo randomizado controlado

Objetivo: evaluar la eficacia analgesica de la lidocaina subcutanea y la analgesia multimodal para la remocion del tubo toracico despues de la cirugia cardiaca. Metodos: sesenta voluntarios fueron asignados aleatoriamente en dos grupos; 30 participantes en el grupo experimental recibieron lidocaina subcutanea al 1%, y 30 controlos recibieron un regimen de analgesia multimodal que comprende agentes antiinflamatorios sistemicos y opioides. La intensidad y calidad del dolor y rasgo y estado de ansiedad se evaluaron. La asociacion entre las variables independientes y el resultado final han sido evaluados por medio de la prueba de Chi-cuadrado con correccion de Yates y la prueba exacta de Fisher. Resultados: los grupos no mostraron diferencias significativas con respecto a la intensidad del dolor despues de la retirada del tubo toracico (p= 0,47). Los descriptores de dolor mas frecuentes informados por los participantes fueron apretado, agudo, punzante, ardiente e insoportable. Conclusion: el presente estudio sugiere que el efecto analgesico de la administracion subcutanea de lidocaina al 1% combinada con la analgesia multimodal es eficaz.