Desenvolvimento de uma formulação cólon específica visando o tratamento da colite ulcerativa

Micro and nanoparticulate systems as drug delivery carriers have achieved successful therapeutic use by enhancing efficacy and reducing toxicity of potent drugs. The improvement of pharmaceutical grade polymers has allowed the development of such therapeutic systems. Microencapsulation is a process in which very thin coatings of inert natural or synthetic polymeric materials are deposited around microsized particles of solids or around droplets. Products thus formed are known as microparticles. Xylan is a natural polymer abundantly found in nature. It is the most common hemicellulose, representing more than 60% of the polysaccharides existing in the cell walls of corn cobs, and is normally degraded by the bacterial enzymes present in the colon of the human body. Therefore, this polymer is an eligible material to produce colon-specific drug carriers. The aim of this study was to evaluate the technological potential of xylan for the development of colon delivery systems for the treatment of inflammatory bowel diseases. First, coacervation was evaluated as a feasible method to produce xylan microcapsules. Afterwards, interfacial cross-linking polymerization was studied as a method to produce microcapsules with hydrophilic core. Additionally, magnetic xylan-coated microcapsules were prepared in order to investigate the ability of producing gastroresistant systems. Besides, the influence of the external phase composition on the production and mean diameter of microcapsules produced by interfacial cross-linking polymerization was investigated. Also, technological properties of xylan were determined in order to predict its possible application in other pharmaceutical dosage forms

Micro and nanosystems for delivering local anesthetics

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

Study of the interaction between cardiolipin bilayers and methylene blue in polymer-based Layer-by-Layer and Langmuir films applied as membrane mimetic systems

An increase of the reports involving mimetic systems has been observed. Briefly, these systems use biological phospholipids to exploit specific interactions between membrane-models and drugs. Here, the Layer-by-Layer (LbL) and Langmuir techniques were used to investigate the interaction between cardiolipin (CLP-negative phospholipid) and a cationic-like drug methylene blue (MB). Supported by a cationic polyelectrolyte (PAH), LbL films containing PAH/(CLP + MB) and PAH/(CLP + MB + AgNP) were grown up to 14 bilayers. The optical microscopy analysis revealed a decrease of the CLP vesicle sizes in the presence of MB as a possible consequence of the MB action onto the mechanical properties of the CLP membrane. From FTIR spectra, changes mainly related to peak position and band intensity and shape were observed in the spectra from PAH/CLP when in the presence of MB. The latter supports that the interactions between the phosphate and amine charged groups from CLP and PAH, respectively, established during the LbL film fabrication, besides the CLP hydrocarbon environment, are influenced by the presence of MB. Using the micro-Raman technique, a chemical mapping was build based on MB spectrum by resonance Raman scattering (RRS) and surface-enhanced resonance Raman scattering (SERRS). The later phenomenon was activated by Ag nanoparticles (AgNPs) trapped within the LbL film allowing collecting spectra for a single bilayer of PAH/(CLP + MB + AgNP). A rough estimation showed a SERRS amplification of 10(3) in comparison to RRS spectra. As a complementary approach, Langmuir films of CLP in the presence of co-spread MB were investigated through surface pressure vs mean molecular area (pi-A) isotherms. The results showed that for concentrations of MB below 100 mol%, the drug is expelled to water subphase for high values of surface pressure (condensed phase). For concentration at 100% and higher, the MB keeps bound to CLP floating monolayer. (C) 2010 Elsevier B.V. All rights reserved.

Drug delivery systems: Past, present, and future

Drug delivery systems are essential components of drugs controlled release. In the last decades, several drug delivery technologies have emerged including capsules, liposomes. microparticles, nanoparticles, and polymers. These components must be biocompatible, biodegradable, and display a desired biodistribution providing a long-term availability of the therapeutic at specific target over time.

Subconjunctival Delivery of Antibiotics in a Controlled-Release System A Novel Anti-infective Prophylaxis Approach for Cataract Surgery

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

A Single Intraoperative Sub-Tenon's Capsule Injection of Triamcinolone and Ciprofloxacin in a Controlled-Release System for Cataract Surgery

PURPOSE. To compare intraoperative injection of triamcinolone and ciprofloxacin in a controlled-release system (DuoCat) with prednisolone and ciprofloxacin eye drops after cataract surgery.METHODS. In this randomized, double-masked, controlled trial, a total of 135 patients undergoing cataract surgery were randomly allocated to two groups: 67 patients treated after surgery with prednisolone 1% and ciprofloxacin 3% eye drops four times daily (week 1), three times daily (week 2), twice daily (week 3), and once daily (week 4) and 0.3% ciprofloxacin drops four times daily (weeks 1 and 2), and 68 patients treated at the end of surgery with a sub-Tenon's injection of 25 mg triamcinolone and 2 mg ciprofloxacin in biodegradable microspheres. The patients were examined on postoperative days 1, 3, 7, 14, and 28. The main outcome measures were postoperative anterior chamber cell and flare, intraocular pressure (IOP), lack of anti-inflammatory response, and presence of infection.RESULTS. No significant differences were observed between the groups in anterior chamber cell (P > 0.14) and flare (P > 0.02) at any postoperative visits. The mean (99% confidence interval) differences in IOP between the prednisolone and triamcinolone groups on days 1, 3, 7, 14, and 28 were -0.4 mm Hg (-2.1 to 1.3), 0.0 mm Hg (-1.4 to 1.3), 0.0 mm Hg (-1.1 to 1.1), -0.2 mm Hg (-1.1 to 0.8), and -0.1 mm Hg (-1.1 to 0.9), respectively. No patient had a postoperative infection.CONCLUSIONS. One injection of DuoCat had a therapeutic response and ocular tolerance that were equivalent to conventional eye drops in controlling inflammation after cataract surgery. (Clinical-Trials. gov number, NCT00431028.) (Invest Ophthalmol Vis Sci. 2009; 50: 3041-3047) DOI: 10.1167/iovs.08-2920

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

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Preparation and characterization of free films of high amylose/pectin mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis

Importance of the field: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Area covered in this review: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.What the reader will gain: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.Take home message: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.

Metronidazole release using natural rubber latex as matrix

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

Modelling post-release survival of reintroduced Red-billed Curassows Crax blumenbachii

Modelling post-release survival probabilities of reintroduced birds can help inform 'soft-release' strategies for avian reintroductions that use captive-bred individuals. We used post-release radiotelemetry data to estimate the survival probabilities of reintroduced captive-bred Red-billed Curassow Crax blumenbachii, a globally threatened Cracid endemic to the Brazilian Atlantic Rainforest. Between August 2006 and December 2008, 46 radiotagged Curassows from the Crax Brazil breeding centre were reintroduced to the Guapiacu Ecological Reserve (REGUA), Rio de Janeiro state, Brazil, in seven different cohorts. Reintroduced birds were most vulnerable during the first 12 months post-release from natural predation, domestic dogs and hunting. Annual post-release survival probability was high (75%) compared with published estimates for other Galliform species. However, when considering survival in all birds transported to REGUA (some birds died before release or were retained in captivity) and not only post-release survival, phi in this study was closer to estimates for other species (60%). The duration of the pre-release acclimatization period within the soft-release enclosure and the size of the released cohorts both positively influenced post-release survival of reintroduced Curassows. Our results are relevant to future Cracid reintroductions and highlight the importance of utilizing post-release monitoring data for evidence-based improvements to soft-release strategies that can significantly enhance the post-release survival of captive-bred birds.

Diffusion-controlled growth of aggregates in layer-by-layer films of poly(o-methoxyaniline)

The adsorption process in layer-by-layer (LBL) films of poly(o-methoxyaniline) alternated with poly(vinyl sulfonic acid) is explained using the Avrami equation. This equation was used due to its mathematical simplicity and adequate description of experimental data in real polymer systems. The Avrami parameters are a convenient means to represent empirical data of crystallization, and if microscopic knowledge is available these parameters can also be associated with adsorption mechanisms. The growth of spherulites in the LBL films was studied as a function of time using atomic force microscopy and the data were used to estimate the number and radii of aggregates, from which the Avrami parameters were determined. We find that the adsorption mechanism may correspond to a tri dimensional, diffusion-controlled growth, with increasing nucleation rate, consistent with results from kinetics of adsorption.

Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia

The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 12 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 12 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1-2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration increased and haematocrit decreased during halothane anaesthesia. The concentrations of met-enkephalin, dynorphin and catecholamines did not change and those of β-endorphin, adrenocorticotrophin, arginine vasopressin and cortisol increased during halothane anaesthesia. Halothane appeared to be a major stimulus to pituitary adrenocortical activation because the adrenocortical secretion was proportional to the amount of halothane inhaled. β-endorphin increased proportionally more than adrenocorticotrophin and their plasma concentrations were not correlated, suggesting that they have independent secretion mechanisms.

Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [ 3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 ± 4.2 vs 8.4 ± 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a single dose significantly enhanced the basal motor activity (38.3 ± 4.5 vs 8.4 ± 3.5 s) and increased the duration of exploratory activity (38.3 ± 4.5 vs 32.1 ± 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and relase assays. The inhibition of uptake and release of [ 3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Release of formaldehyde by 4 endodontic sealers

Objective. The purpose of this study was to evaluate the release of formaldehyde by some root canal filling materials. Study design. Two older endodontic sealers, AH 26 and Endomethasone, and 2 recently available sealers, AH Plus and Top Seal, were analyzed. Infrared and electronic spectroscopy were used to determine formaldehyde content after set of the materials. Results. Analysis showed that the AH 26 and Endomethasone sealers released formaldehyde. Although the AH Plus and Top Seal sealers have similar chemical composition, they released formaldehyde in a minimal concentration. Conclusions. The AH 26 and Endomethasone sealers released formaldehyde after setting; however, a minimum release was observed for the AH Plus and Top Seal sealers. Copyright © 1999 by Mosby, Inc.