Ligand Exchange Inducing Efficient Incorporation of CisPt Derivatives into Ureasil-PPO Hybrid and Their Interactions with the Multifunctional Hybrid Network

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 Å resolution

Background: Glucosamine 6-phosphate deaminase from Escherichia coli is an allosteric hexameric enzyme which catalyzes the reversible conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate and ammonium ion and is activated by N-acetyl-D-glucosamine 6-phosphate. Mechanistically, it belongs to the group of aldose-ketose isomerases, but its reaction also accomplishes a simultaneous amination/deamination. The determination of the structure of this protein provides fundamental knowledge for understanding its mode of action and the nature of allosteric conformational changes that regulate its function. Results: The crystal structure of glucosamine 6-phosphate deaminase with bound phosphate ions is presented at 2.1 Å resolution together with the refined structures of the enzyme in complexes with its allosteric activator and with a competitive inhibitor. The protein fold can be described as a modified NAD-binding domain. Conclusions: From the similarities between the three presented structures, it is concluded that these represent the enzymatically active R state conformer. A mechanism for the deaminase reaction is proposed. It comprises steps to open the pyranose ring of the substrate and a sequence of general base-catalyzed reactions to bring about isomerization and deamination, with Asp72 playing a key role as a proton exchanger.

Sistemas para liberação colônica: Uma alternativa para a veiculação de fármacos para efeito local ou sistêmico

Problems related to the systemic administration of drugs, such as biodistribution, difficulty of targeting, necessity of high doses to achieve adequate levels of the drug in specific sites, toxicity, and undesirable side effects have lead to the development of systems able to direct the drug to specific sites in the body. Among the possible organs to the targeting of drugs, the colon can be used for local and systemic therapies. By developing such systems some models have been tested, using pH dependent release, release controlled by enzymatic degradation, time controlled release systems and pressure controlled release systems. This review presents an overview of the colonic release of drugs and the strategies used to achieve such targeting.

Encapsulação da rifampicina em matrizes poliméricas flutuantes obtidas por liofilização a partir de metilcelulose e ftalato de hidroxipropilmetilcelulose. Avaliação da liberação in vitro

Floating multiparticles for oral administration with different compositions were studied from a matricial polymeric system to obtain sustained release. The polymers used in the multiparticles constitution were methylceullose (MC) and hydroxypropylmethylcelullose phthalate (HPMCP) in several proportions. Spherical and isolated structures were obtained using HPMCP/MC in the range from 1:3 to 1: 13. The diameters of the floating multiparticles were in the range from 3 to 3.25 mm, while the non-floating particles were between 1.75 and 2.1 mm. The morphological analysis by confocal microscopy showed that the probable mechanism of drug release was the diffusion from the inner of particles to external media. The encapsulation of hydrophilic model substances (tartrazin and bordeaux S), showed that the maximum incorporation was about 38%, while for the lipophilic model substances (rifampicin) was 45%. The in vitro release of rifampicin in acid medium was dependent on the ratio HPMCP/MC. In alkaline medium the release followed a two-step profile, with slow release in the initial times and subsequent increase in the higher times The initial drug delivery profile was not dependent on the MC/HPMCP ratio and can be related with the release of the antibiotic from multiparticle inner caused by the swelling of polymers by the presence of water in the system. However, afterwards the release proceeds with typical profile of process involving hydrogels systems.

Polissacarídeos biodegradáveis úteis para a preparação de sistemas de liberação controlada de fármacos. Parte 1: Quitosana

Due to an increasing interest, a vast number of biodegradable polymers have been obtained recently. Polymers naturally produced, such as cellulose, starch, chitosan and alginate, represent biodegradable materials, with low toxicity and low cost. Among polysaccharides, chitosan has been of great interest of the industrial and academic research, due to its special qualities of biodegradability and biocompatibility and, on the other hand, to the versatility of its use in several physical forms and products. A significant growth in the development of new dosage forms capable to deliver the drug in a controlled and targeted way has been observed in these last years. Such pharmaceutical forms search, mainly, the reduction of the dose administered and of the administration frequency, the reduction of adverse side effects and, consequently, a better patient compliance. The present paper describes the use of chitosan in pharmaceutical products, especially in drug controlled delivery systems.

Microemulsões: Estrutura e aplicações como sistema de liberação de fármacos

Depending on formula composition, microemulsions may be used as a vehicle for drug administration. In this work the main applicable parameters used in the development of pharmaceutical microemulsions (ME) are analyzed. The conceptual description of the system, theoretical parameters related to formation of internal phases and some aspects of ME stability are described. The pseudo ternary phase diagram is used to characterize ME boundaries and to describe different structures in several regions of the diagram. Some applications of ME as drug delivery systems for different administration routes are also analyzed. ME offer advantages as drug delivery systems, because they favor drug absorption, being in most cases faster and more efficient than other methods in delivering the same amount of drug.

Antenatal corticosteroid use and clinical evolution of preterm newborn infants

Objectives: To describe the use of antenatal corticosteroid and clinical evolution of preterm babies. Methods: An observational prospective cohort study was carried out. All 463 pregnant women and their 514 newborn babies with gestational age ranging from 23 to 34 weeks, born at the Brazilian Neonatal Research Network units, were evaluated from August 1 to December 31, 2001. The data were obtained through maternal interview, analysis of medical records, and follow-up of the newborn infants. Data analysis was performed with the use of chi-square, t Student, Mann-Whitney, and ANOVA tests and multiple logistic regression, with level of significance set at 5%. Results: Treatment was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented better Apgar scores at the 1st and 5th minute, reduced need for intervention in the delivery room and lower SNAPPE II. They were born with higher birth weight, longer gestational age and needed less surfactant use, ventilation, and oxygenation time. After multiple logistic regression, the use of antenatal corticosteroid independently improved birth conditions, decreased ventilation time, being related to increased occurrence of neonatal sepsis. Conclusions: The use of corticosteroid was associated with better prenatal care and birth conditions, better preterm evolution but higher risk of infection. Copyright © 2004 by Sociedade Brasileira de Pediatria.

Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: Comparative effects of helium and nitrogen

Background: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. Methods: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. Results: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 ± 13 vs. 383 ± 84 μg/g in noninfected piglets and 10 ± 3 vs. 129 ± 108 μg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 ± 141 μg/g; P < 0.001) and no significant change in infected piglets (111 ± 104 μg/g). Conclusion: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Estudos sobre liberação controlada e vetorização de drogas através de lipossomas

The text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to infectious diseases. Liposomes have several pharmaceutical applications and this manuscript is primarily focused on the potential of this colloidal system as an antibiotic carrier system and of administration through several accesses via to organism. Numerous case studies in which liposomes have successfully been used to improve pharmacological drug effect are presented. Mechanisms involved in drug delivery, application possibilities, research and development and efforts to reach these objectives are discussed. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Ethylcelullose microspheres containing sodium diclofenac: Development and characterization

The objective of the present study was the development and characterization of ethylcellulose microspheres containing diclofenac and the determination of the in vitro drug release profile. Microspheres were prepared by emulsification/solvent evaporation method using ethyl acetate as solvent for the polymer and water as non solvent. The microspheres were characterized by morphologic and granulometric analyses. The amount of encapsulated drug as well as its release profile in vitro were also determined. The product obtained was microparticles with smooth surface and narrow size distribution, about 50% of the particles being smaller than 5 μm. The methodology used allowed drug encapsulation with a good yield and the system provided a controlled release of diclofenac.

Estratégias biotecnológicas para a liberação controlada de antígenos e adjuvantes em vacinas através de lipossomas

Liposomes (LP) are colloidal systems with ability to compartmentalize therapeutic molecules in order to improve biological activity, decreases the potential toxicity, and to obtain prolonged effect. In this work it was discussed the role of the various liposomes types to encapsulate drug molecules able to provoke some immunological response (drugs, antigens and DNA). The effect of the liposomes and the parameters about the formation of the structures are also analyzed. Detailed literature review shows that, depending on the molecules polarity and the superficial charge of the liposome structures, the system may be efficiently used to optimize the therapeutic effects by means of the release control or through a drug delivery mechanism.

Magnetic multiparticulate colonic delivery systems evaluated by AC Biosusceptometry

The biomagnetic technique called Alternate Current Biosusceptometry (ACB) is a proposal to evaluate a multiparticulate drug delivery system in the human gastrointestinal tract. Results show that ACB was able to quantify the gastrointestinal transit and spreading of the magnetic material and is an attractive tool for pharmaceutical research. © 2007.

Ureasil-polyether hybrid film-forming materials

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules. © 2012 Elsevier B.V.

Development and in vitro evaluation of coated pellets containing chitosan to potential colonic drug delivery

In this work pellets containing chitosan for colonic drug delivery were developed. The influence of the polysaccharide in the pellets was evaluated by swelling, drug dissolution and intestinal permeation studies. Drug-loaded pellets containing chitosan as swellable polymer were coated with an inner layer of Kollicoat® SR 30 D and an outer layer of the enteric polymer Kollicoat® MAE 30 DP in a fluidized-bed apparatus. Metronidazole released from pellets was assessed using Bio-Dis dissolution method. Swelling, drug release and intestinal permeation were dependent on the chitosan and the coating composition. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. The film coating was found to be the main factor controlling the drug release and the chitosan controlling the drug intestinal permeation. Coated pellets containing chitosan show great potential as a system for drug delivery to the colon. © 2012 Elsevier Ltd.