The effect of the degree of hydrolysis of the PVA and the plasticizer concentration on the color, opacity, and thermal and mechanical properties of films based on PVA and gelatin blends

The objective of this work was to study the color, opacity, crystallinity, and the thermal and mechanical properties of films based on blends of gelatin and five different types of PVA [poly(vinyl alcohol)], with and without a plasticizer. The effect of the degree of hydrolysis of the PVA and the glycerol concentration on these properties was studied using colorimetry, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile mechanical tests. All films were essentially colorless (Delta E* < 5) and with low opacity ( Y <= 2.1). The DSC results were typical of partially crystalline materials, showing some phase separation characterized by a glass transition (T(g) = 40-55 degrees C), related to the amorphous part of the material, followed by two endothermic peaks related to the melting (T(m) = 100-160 and 170-210 degrees C) of the crystallites. The XRD results confirmed the crystallinity of the films. The film produced with PVA Celvol((R)) 418 (DH = 91.8%) showed the highest tensile resistance (tensile strength = 38 MPa), for films without plasticizer. However, with glycerol, the above-mentioned PVA and the PVA Celvol((R)) 504 produced the least resistant films of all the PVA types. But, although the mechanical properties of the blended films depended on the type of PVA used, there was no direct relationship between these properties and the degree of hydrolysis of the PVA. The properties studied were more closely dependent on the glycerol concentration. Finally, the mechanical resistance of the films presented a linear relationship with the glass transition temperature of the films. (c) 2007 Elsevier Ltd. All rights reserved.

Polímeros sintéticos biodegradáveis: matérias-primas e métodos de produção de micropartículas para uso em drug delivery e liberação controlada

Micropartículas produzidas a partir de polímeros sintéticos têm sido amplamente utilizadas na área farmacêutica para encapsulação de princípios ativos. Essas micropartículas apresentam as vantagens de proteção do princípio ativo, mucoadesão e gastrorresistência, melhor biodisponibilidade e maior adesão do paciente ao tratamento. Além disso, utiliza menores quantidade de princípio ativo para obtenção do efeito terapêutico proporcionando diminuição dos efeitos adversos locais, sistêmicos e menor toxidade. Os polímeros sintéticos empregados na produção das micropartículas são classificados biodegradáveis ou não biodegradáveis, sendo os biodegradáveis mais utilizados por não necessitam ser removidos cirurgicamente após o término de sua ação. A produção das micropartículas poliméricas sintéticas para encapsulação tanto de ativos hidrofílicos quanto hidrofóbicos pode ser emulsificação por extração e/ou evaporação do solvente; coacervação; métodos mecânicos e estão revisados neste artigo evidenciando as vantagens, desvantagens e viabilidade de cada metodologia. A escolha da metodologia e do polímero sintético a serem empregados na produção desse sistema dependem da aplicação terapêutica requerida, bem como a simplicidade, reprodutibilidade e factibilidade do aumento de escala da produção.

The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

Natural rubber latex used as drug delivery system in guided bone regeneration (GBR)

In this work, we propose natural rubber latex (NRL) membranes as a protein delivery system. For this purpose Bovine Serum Albumin (BSA) was incorporated into the latex solution for in vitro protein delivery experiments. Different polymerization temperatures were used, from -10 to 27 °C, in order to control the membrane morphology. These membranes were characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), as well as the Lowry Method to measure the BSA release. SEM and AFM microscopy analysis showed that the number, size and distribution of pores in NRL membranes can be varied, as well as its overall morphology. We have found that the morphology of the membrane is the predominant factor for higher protein release, compared with pore size and number of pores. Results demonstrated that the best drug-delivery system was the membrane polymerized at RT (27 °C), which does release 66% of its BSA content for up to 18 days. Our results indicate that NRLb could be used in the future as an active membrane that could accelerate bone healing in GBR.

Drug consumption among medical students in São Paulo, Brazil: influences of gender and academic year

OBJECTIVE: To analyze alcohol, tobacco and other drug use among medical students. METHOD: Over a five-year period (1996-2001), we evaluated 457 students at the Universidade de São Paulo School of Medicine, located in São Paulo, Brazil. The students participated by filling out an anonymous questionnaire on drug use (lifetime, previous 12 months and previous 30 days). The influence that gender and academic year have on drug use was also analyzed. RESULTS: During the study period, there was an increase in the use of illicit drugs, especially inhalants and amphetamines, among the medical students evaluated. Drug use (except that of marijuana and inhalants) was comparable between the genders, and academic year was an important influencing factor. DISCUSSION: Increased inhalant use was observed among the medical students, especially among males and students in the early undergraduate years. This is suggestive of a specific behavioral pattern among medical students. Our findings corroborate those of previous studies. CONCLUSION: Inhalant use is on the rise among medical students at the Universidade de São Paulo School of Medicine. Because of the negative health effects of illicit drug use, further studies are needed in order to deepen the understanding of this phenomenon and to facilitate the development of preventive measures.

High prevalence of drug-resistant tuberculosis and other mycobacteria among HIV-infected patients in Brazil: a systematic review

There is a little-noticed trend involving human immunodeficiency virus (HIV)-infected patients suspected of having tuberculosis: the triple-treatment regimen recommended in Brazil for years has been potentially ineffective in over 30% of the cases. This proportion may be attributable to drug resistance (to at least 1 drug) and/or to infection with non-tuberculous mycobacteria. This evidence was not disclosed in official statistics, but arose from a systematic review of a few regional studies in which the diagnosis was reliably confirmed by mycobacterial culture. This paper clarifies that there has long been ample evidence for the potential benefits of a four-drug regimen for co-infected patients in Brazil and it reinforces the need for determining the species and drug susceptibility in all positive cultures from HIV-positive patients.

Hydrolysis of methyl benzoate from Piper arboreum by Naupactus bipes beetle

A new natural product was isolated from Piper arboreum (Piperaceae) leaves, the methyl 3-geranyl-4-hydroxybenzoate (1). The metabolism of P. arboreum leaves by Naupactus bipes beetle (Germar, 1824 - Coleoptera: Curculionidae) led to the hydrolysis of 1 to 3-geranyl-4-hydroxybenzoic acid (2). The structures of both compounds were determined based on spectroscopic analysis (¹H and 13C NMR, MS, and IR).

Conducting polymer- hydrogel blends for electrochemically controlled drug release devices

Blends formed by electrochemical polymerization of polypyrrole (PPy) into polyacrylamide (PAAm) hydrogels were used as devices for controlled drug release. The influence of several parameters in the synthesis, such as type of hydrogel matrix and polymerization conditions was studied by using a fractional factorial design. The final goal was to obtain an adequate device for use in controlled release tests, based on electrochemical potential control. For controlled release tests, Safranin was used as model drug and release curves (amount of drug vs. time) have shown that these blends are promising materials for this use. The optimized blends obtained were characterized by cyclic voltammetry and Raman spectroscopy.

Pharmacist professionals in the prevention of drug abuse: updating roles, and opportunities

The objective of this paper was to prepare and provide resources to pharmacists and other healthcare professionals, enabling them to carry out a critical analysis on drug abuse, acquiring knowledge in several areas that effectively contribute to their personal development in this professional field. Professionals play a crucial role in the reduction and prevention of substances abuse, since they are able to advise patient about illicit drugs, psychotropic medicines and alcohol abuse. There is an urgent need to specialize pharmacists to act in the national public health service and contribute to actions aimed at the surrounding community.

Topochemical distribution of lignin and hydroxycinnamic acids in sugar-cane cell walls and its correlation with the enzymatic hydrolysis of polysaccharides

Background: Lignin and hemicelluloses are the major components limiting enzyme infiltration into cell walls. Determination of the topochemical distribution of lignin and aromatics in sugar cane might provide important data on the recalcitrance of specific cells. We used cellular ultraviolet (UV) microspectrophotometry (UMSP) to topochemically detect lignin and hydroxycinnamic acids in individual fiber, vessel and parenchyma cell walls of untreated and chlorite-treated sugar cane. Internodes, presenting typical vascular bundles and sucrose-storing parenchyma cells, were divided into rind and pith fractions. Results: Vascular bundles were more abundant in the rind, whereas parenchyma cells predominated in the pith region. UV measurements of untreated fiber cell walls gave absorbance spectra typical of grass lignin, with a band at 278 nm and a pronounced shoulder at 315 nm, assigned to the presence of hydroxycinnamic acids linked to lignin and/or to arabino-methylglucurono-xylans. The cell walls of vessels had the highest level of lignification, followed by those of fibers and parenchyma. Pith parenchyma cell walls were characterized by very low absorbance values at 278 nm; however, a distinct peak at 315 nm indicated that pith parenchyma cells are not extensively lignified, but contain significant amounts of hydroxycinnamic acids. Cellular UV image profiles scanned with an absorbance intensity maximum of 278 nm identified the pattern of lignin distribution in the individual cell walls, with the highest concentration occurring in the middle lamella and cell corners. Chlorite treatment caused a rapid removal of hydroxycinnamic acids from parenchyma cell walls, whereas the thicker fiber cell walls were delignified only after a long treatment duration (4 hours). Untreated pith samples were promptly hydrolyzed by cellulases, reaching 63% of cellulose conversion after 72 hours of hydrolysis, whereas untreated rind samples achieved only 20% hydrolyzation. Conclusion: The low recalcitrance of pith cells correlated with the low UV-absorbance values seen in parenchyma cells. Chlorite treatment of pith cells did not enhance cellulose conversion. By contrast, application of the same treatment to rind cells led to significant removal of hydroxycinnamic acids and lignin, resulting in marked enhancement of cellulose conversion by cellulases.

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

Nitrofurazone (NF) presents activity against Chagas' disease, yet it has a high toxicity. Its analog, hydroxymethylnitrofurazone (NFOH), is more potent against Trypanosoma cruzi and much less toxic than the parent drug, NF. The electrochemical reduction of NFOH in an aqueous medium using a glassy carbon electrode (GCE) is presented. By cyclic voltammetry in anacidic medium, one irreversible reduction peak related to hydroxylamine derivative formation was registered, being linearly pH dependent. However, from pH > 7, a reversible reduction peak at a more positive potential appears and corresponds to the formation of a nitro radical anion. The radical-anion kinetic stability was evaluated by Ip(a)/Ip(c) the current ratio of the R-NO(2)/R-NO(2)-redox couple. The nitro radical anion decays with a second-order rate constant (k(2)) of 6.07, 2.06, and 1.44(X 10(3)) L mol(-1) s(-1) corresponding to pH 8.29, 9.29, and 10.2, respectively, with a corresponding half-time life (t(1/2)) of 0.33, 0.97, and 1.4 s for each pH value. By polishing the GCE surface with diamond powder and comparing with the GCE surface polished with alumina, it is shown that the presence of alumina affects the lifetime of the nitro radical anion. (C) 2009 The Electrochemical Society. [DOI: 10.1149/1.3130082] All rights reserved.

Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system

Background: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich's tumors by the magnetohyperthermia procedure. Methods and materials: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. Results: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). Conclusion: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy.

Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

Background: Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods: B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results: Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19Arf and nutlin-3. Conclusions: To the best of our knowledge, this is the first study to apply both p19Arf and nutlin-3 for the stimulation of p53 activity. These results support the notion that a p53 responsive vector may prove to be an interesting gene transfer tool, especially when combined with p53- activating agents, for the treatment of tumors that retain wild-type p53.

Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

Background: Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs). The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. Methodology/Principal Findings: In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP) and BnP1 (weakly hemorrhagic SVMP) using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition, BnP1 did not accumulate in the tissues. Conclusions/Significance: These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the difference between hemorrhagic and non-hemorrhagic SVMPs, improving the understanding of snakebite pathology.

Increasing the symmetry of drug crystals: a monoclinic conformational polymorph of the platelet antiaggregating agent ticlopidine hydrochloride

Ticlopidine hydrochloride (TICLID (R)) is a platelet antiaggregating agent whose use as a potent antithrombotic pharmaceutical ingredient is widespread, even though this drug has not been well characterized in the solid state. Only the crystal phase used for drug product manufacturing is known. Here, a new polymorph of ticlopidine hydrochloride was discovered and its structure was determined. While the antecedent polymorph crystallizes in the triclinic space group P (1) over bar, the new crystal phase was solved in the monoclinic space group P2(1)/c. Both polymorphs crystallize as racemic mixtures of enantiomeric (ticlopidine)(+) cations. Detailed geometrical and packing comparisons between the crystal structures of the two polymorphs have allowed us to understand how different supramolecular architectures are assembled. It was feasible to conclude that the main difference between the two polymorphs is a rotation of about 120 degrees on the bridging bond between the thienopyridine and o-chlorobenzyl moieties. The differential o-chlorobenzyl conformation is related to changeable patterns of weak intermolecular contacts involving this moiety, such as edge-to-face Cl center dot center dot center dot pi and C-H center dot center dot center dot pi interactions in the new polymorph and face-to-face pi center dot center dot center dot pi contacts in the triclinic crystal phase, leading to a symmetry increase in the ticlopidine hydrochloride solid state form described for the first time in this study. Other conformational features are slightly different between the two polymorphs, such as the thienopyridine puckerings and the o-chlorophenyl orientations. These conformational characteristics were also correlated to the crystal packing patterns.