Sistemas microemulsionados como carreador lipídico para fármacos insolúveis

Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market

Novo sistema de aplicação de drogas em cirurgias oftalmológicas

The topical corneal application of antimitotic mitomycin-C (MMC) during refractive surgery is still characterized by a lack of standardization and considerable empirism. For this reason the creation of a system capable of reliable drug delivery represents a beneficial innovation for patients submitted to these procedures. Objective: Elaborate a new MMC delivery system during the transoperatory period of photorefractive keratectomy (PRK) followed by patent application. Methods: The project consists of an in vitro experimental study to create an MMC (0.02%) release system. The drug was impregnated in sterile Whatman® 41 paper filter discs with a diameter of 8 mm. After drying, the discs were applied to antibiogram plates seeded with Staphylococcus epidermidis (American Type Culture Collection ATCC 12228), followed by the addition of a drop of sterile water. At the end of 1 minute, the discs were removed and the plates incubated for 48 hours at 35oC. Mean drop volume in the collyrium flasks was measured using analytical balance weighing. The inhibition halo (mm) was correlated with the MMC impregnated into the disc. After completion of the invention design a patent application was lodged at the National Institute of Industrial Property. Results: The correspondence between MMC-produced inhibition halos indicated that a dose of 16μg was ideal for impregnating into the discs. The mean drop volume obtained from the collyrium flasks was 37.7 μL. A minute after the application of one drop of balanced saline solution, the system released an adequate concentration for PRK surgery. Conclusion: A new MMC delivery system was created for transoperatory application in photorefractive keratectomy (PRK). Publication of the patent application (number PI 0704739-8) gives the authors exclusive intellectual property rights. The study was sponsored by Ophthalmos Indústria e Comércio de Produtos Farmacêuticos S.A. (São Paulo-SP, Brazil) and received the indispensable scientific contribution of researchers from the fields of Pharmacy, Medicine, Biology, Statistics and Law, characterizing the work as multidisciplinary, in accordance with norms established by the Postgraduate Health Sciences Program of the Federal University of Rio Grande do Norte (UFRN)

Desenvolvimento de sistemas magnéticos com potencialidades terapêuticas para vetorização de fármacos

Magnetic targeting is being investigated as a means of local delivery of drugs, combining precision, minimal surgical intervention, and satisfactory concentration of the drug in the target region. In view of these advantages, it is a promising strategy for improving the pharmacological response. Magnetic particles are attracted by a magnetic field gradient, and drugs bound to them can be driven to their site of action by means of the selective application of magnetic field on the desired area. Helicobacter pylori is the commonest chronic bacterial infection. The treatment of choice has commonly been based upon a triple therapy combining two antibiotics and an anti-secretory agent. Furthermore, an extended-release profile is of utmost importance for these formulations. The aim of this work was to develop a magnetic system containing the antibiotic amoxicillin for oral magnetic drug targeting. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. The second step was coating the particles and amoxicillin with Eudragit® S-100 by spray-drying technique. The system obtained demonstrated through the characterization studies carried out a possible oral drug delivery system, consisting in magnetite microparticles and amoxicillin, coated with a polymer acid resistant. This system can be used to deliver drugs to the stomach for treatment of infections in this organ. Another important finding in this work is that it opens new prospects to coat magnetic microparticles by the technique of spray-drying.

Micropartículas poliméricas à base de xilana e Eudragit® S-100 contendo mesalazina visando à liberação cólon-específica

Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

Nanopartíulas de magnetita com oxacilina obtida por moagem de alta energia para aplicações biomédicas

The drug targeting has been the subject of extensive studies in order to develop site-specific treatments that minimize side effects and become more effective anticancer therapy. Despite considerable interest in this class, drugs like antibiotics also have limitations, and have been neglected. Using new pharmaceutical technologies, the use of magnetic vectors appear as promising candidate for drug delivery systems in several studies. Small magnetic particles bound to the drug of interest can be modulated according to the orientation of a magnet outside the body, locating and holding in a specific site. In this work, we propose the use of High Energy Milling (HEM) for synthesis of a magnetic vector with characteristics suitable for biomedical applications by intravenous administration, and for the formation of an oxacillin-carrier complex to obtain a system for treating infections caused by Staphylococcus aureus. The results of the variation of milling time showed that the size and structural properties of the formed material change with increasing milling time, and in 60 hours we found the sample closest to the ideal conditions of the material. The vector-drug system was studied in terms of structural stability and antimicrobial activity after the milling process, which revealed the integrity of the oxacillin molecule and its bactericidal action on cultures of Staphylococcus aureus ATCC

Micropartículas de poli (ácido láctico)/ poloxámero obtids por spray drying para liberação modificada de metotrexatro

New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic® (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application

Utilização intracoágulo de espuma fibrinolítica - preparação, caracterização e atividade in vitro de uma espuma de estreptoquinase e proposta de uma nova abordagem terapêutica

Foam was developed as a novel vehicle for streptokinase with the purpose of increasing the contact time and area between the fibrinolytic and the target thrombus, which would lead to a greater therapeutic efficacy at lower doses, decreasing the drug s potential to cause bleeding. Fibrinolytic foams were prepared using CO2 and human albumin (at different v:v ratios), as the gas and liquid phases, respectively, and streptokinase at a low total dose (100,000 IU) was used as fibrinolytic agent conveyed in 1 mL of foam and in isotonic saline solution. The foams were characterized as foam stability and apparent viscosity. The thrombolytic effect of the streptokinase foam was determined in vitro as thrombus lysis and the results were compared to those of a fibrinolytic solution (prepared using the same dose of streptokinase) and foam without the fibrinolytic. In vitro tests were conducted using fresh clots were weighed and placed in test tubes kept at 37 ° C. All the samples were injected intrathrombus using a multiperforated catheter. The results showed that both foam stability and apparent viscosity increased with the increase in the CO2:albumin solution ratio and therefore, the ratio of 3:1 was used for the incorporation of streptokinase. The results of thrombus lysis showed that the streptokinase foam presented the highest thrombolytic activity (44.78 ± 9.97%) when compared to those of the streptokinase solution (32.07 ± 3.41%) and the foam without the drug (19.2 ± 7.19%). We conclude that fibrinolytic foam showed statistically significant results regarding the enhancement of the lytic activity of streptokinase compared to the effect of the prepared saline solution, thus it can be a promising alternative in the treatment of thrombosis. However, in vivo studies are needed in order to corroborate the results obtained in vitro

Isolation of nanocellulose from pineapple leaf fibres by steam explosion

Steam explosion process is employed for the successful extraction of cellulose nanofibrils from pineapple leaf fibres for the first time. Steam coupled acid treatment on the pineapple leaf fibres is found to be effective in the depolymerization and defibrillation of the fibre to produce nanofibrils of these fibres. The chemical constituents of the different stages of pineapple fibres undergoing treatment were analyzed according to the ASTM standards. The crystallinity of the fibres is examined from the XRD analysis. Characterization of the fibres by SEM. AFM and TEM supports the evidence for the successful isolation of nanofibrils from pineapple leaf. The developed nanocellulose promises to be a very versatile material having the wide range of biomedical applications and biotechnological applications, such as tissue engineering, drug delivery, wound dressings and medical implants. (C) 2010 Elsevier Ltd. All rights reserved.

On the release of metronidazole from natural rubber latex membranes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nitric oxide release using natural rubber latex as matrix

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Zidovudine-Loaded PLA and PLA-PEG Blend Nanoparticles: Influence of Polymer Type on Phagocytic Uptake by Polymorphonuclear Cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Improvement of antischistosomal activity of praziquantel by incorporation into phosphatidylcholine-containing liposomes

Praziquantel (PZQ) is effective against all known species of Schistosomes that infect humans. The failure of mass treatment of schistosomiasis has been attributed to the fact that therapy is not sufficiently long-lasting. This effect may be due to the low bioavailability of PZQ that has a low hydrosolubility and fast metabolism. Liposomes have been used to prolong drug levels. reduce the side effects, direct drugs to specific sites and increase bioavailability after administration. The aim of this work was to study the effect of phosphatidylcholine (PC)-containing liposomes to vehiculate PZQ to improve the treatment of schistosomiasis. The in vitro Study was carried out using Schistosoma mansoni parasites recovered by perfusion from the hepatic portal system of infected mice. Suspensions of liposomes with PZQ and free PZQ were administered p.o. in mice after 14 days of infection. The effect of both preparations in vitro on S. mansoni culture was similar. In the in vivo test, PZQ-liposomes caused a decrease in amounts of eggs and parasites. Liposomes improve the antischistosomal activity of praziquantel. This can be used as a starting point to investigate alternative administration routes or dosage forms and to examine the mechanism of intestinal absorption of PRZ © 2005 Elsevier B.V. All rights reserved.

Inclusion complex of piroxicam with beta-cyclodextrin and incorporation in hexadecyltrimethylammonium bromide based microemulsion

The interaction of piroxicam with beta-cyclodextrin (beta-CD), hexadecyltrimethylammonium bromide-based microemulsion (ME), and ME in the presence of beta-CD aimed at the optimization of topical drug delivery was studied. UV-VIS absorption spectra at pH 5.5 were obtained with and without beta-CD and ME. The stability constant (K) values for the piroxicam/beta-CD complex in the pH range 4.5-6.0 varied from 87 to 29 M-1. The cationic microemulsion was characterized by pseudo-ternary phase diagram. The association constant (K-s) of piroxicam/ME was determined using the framework of the pseudophase model. The value of K-s obtained for piroxicam at pH 5.5 was 132 M-1. At the same pH, the value of K-s for the incorporation of piroxicam/beta-CD complex in the ME was 150 M-1. (C) 1999 Elsevier B.V. B.V. All rights reserved.

Semisolid systems containing propolis for the treatment of periodontal disease: In vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G ''), and dynamic viscosity (n') at 5 degrees C, G '' exceeded G'. At 25 and 37 degrees C, n' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation. (c) 2007 Wiley-Liss, Inc.

Alginate-chitosan systems: In vitro controlled release of triamcinolone and in vivo gastrointestinal transit

The aim of this study was to develop multiparticulate therapeutic systems of alginate (AL) and chitosan (CS) containing triamcinolone (TC) to colonic drug delivery. Multiparticulate systems of AL-CS, prepared by a complex coacervation/ionotropic gelation method, were characterized for morphological and size aspects, swelling degree, encapsulation content and efficiency, in vitro release profile in different environments simulating the gastrointestinal tract (GIT) and in vivo gastrointestinal transit. The systems showed suitable morphological characteristics with particle diameters of approximately 1.6 mm. In simulated gastric environment, at pH 1.2, the capsules presented low degree of swelling and in vitro release of drug. A higher swelling degree was observed in simulated enteric environment, pH 7.5, followed by erosion. Practically all the drug was released after 6 h of in vitro assay. The in vivo analysis of gastrointestinal transit, carried out in rats, showed that the systems passed practically intact through the stomach and did not show the same profile of swelling observed in the in vitro tests. It was possible to verify the presence of capsules in the colonic region of GIT. The results indicate that AL-CS multiparticulate systems can be used as an adjuvant for the preparation of therapeutic systems to colonic delivery of drugs. (C) 2010 Elsevier Ltd. All rights reserved.