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.

Síndrome das pernas inquietas: Diagnóstico e tratamento. Opinião de especialistas Brasileiros

This article contains the conclusions of the November 17-18, 2006 meeting of the Brazilian Study Group of Restless Legs Syndrome (GBE-SPI) about diagnosis and management of restless legs syndrome (RLS). RLS is characterized by abnormal sensations mostly but not exclusively in the legs which worsen in the evening and are improved by motion of the affected body part. Its diagnosis is solely based on clinical findings. Therapeutic agents with efficacy supported by Class I studies are dopamine agonists, levodopa and gabapentine. Class II studies support the use of slow release valproic acid, clonazepan and oxycodone. The GBE-SPI recommendations for management of SPI are sleep hygiene, withdrawal of medications capable of worsening the condition, treatment of comorbidities and pharmacological agents. The first choice agents are dopaminergic drugs, second choice are gabapentine or oxycodone, and the third choice are clonazepan or slow release valproic acid.

Cloreto de potássio revestido em efeito residual no feijoeiro de inverno irrigado na região de cerrado

In order to maintain the nutrients available to plants have been studied controlled release fertilizers. In this context, the objective was to evaluate the residual effect of doses of potassium chloride, coated or not, applied in the corn crop, regarding the crop components and grains yield of irrigated winter common bean, cultivated in followed, in Cerrado region. The experiment was conducted in Selvíria - MS, Brazil, 51°22- west longitude and 20°22- south latitude, in a clayey Oxisol, in 2009 and 2010. A randomized block design with four repetitions was used, disposed in a factorial scheme 4 x 2, being: four K2O doses (0, 40, 80 and 120 kg ha-1) and two potassium sources (potassium chloride and coated potassium chloride by polymers) applied at sowing in the corn crop. The coated potassium chloride by polymers have the same residual effect as conventional KCl, because it provides results similar for the K and chlorophyll leaf contents, crop components and grains yield of winter common bean irrigated. The increment of potassium doses in the previous crop (corn) have residual effect, because it influenced positively the number of grains per plant in 2009 and increased linearly the chlorophyll leaf content and the grains yield of winter common bean irrigated in 2010, regardless of the source used for K.

Fontes e épocas de aplicação de nitrogênio em trigo em plantio direto no cerrado

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

Doses de lodo de esgoto compostado em produção de tapete de grama esmeralda imperial

The efficiency of nitrogen fertilization for sod production can be increased by using slow-release sources such as sewage sludge compost, which, due to its characteristics can be a substitute of part or all inorganic fertilization for grass. No results were found for the use of sludge compost in sod production in Brazil. This study evaluated the effect of rates of sewage sludge compost on the production of zoysiagrass. Treatments consisted of five rates of composted sewage sludge compost (0, 12, 24, 36 and 48 Mg ha-1, on a dry basis), plus a treatment of inorganic fertilization (300 kg ha-1 N, 80 kg ha-1 P2O5, and 200 kg ha-1 K2O). The results indicated different mineralization rates of the organic compounds present in the sludge; 120 days after sludge application, more Mg (100 %), K (90 %) and N (67 %) has been released than S (57 %), P (40 %) and Ca (31 %). The use of composted sewage sludge for zoysiagrass adequately supplied nutrients when applied to the soil surface at rates more than 36 Mg ha-1. After sod cutting, the rates of sewage sludge compost provided a linear increase in potential soil acidity, soil contents of OM, P, S, Fe, Cu, Mn, Zn, Cu and Ni, and linear decrease in pH, soil concentration of Ca and Mg and base saturation. Compost rates, increasing from 0 to 48 Mg ha-1, reduced the sod mass, reaching values of 4.0 kg/sod at the highest rate. High compost doses (36 and 48 Mg ha-1, respectively) also induced the highest resistance, with values in the order of 35 and 33 kgf.

Adubação com KCl revestido na cultura do milho no Cerrado

The use of coated potassium chloride can provide greater absorption of potassium resulting in the alteration of leaf contents, production components and grain yield. The objective of this study was to evaluate the effect of potassium doses using potassium chloride conventional or coated by polymer, in the corn crop under conditions of brazilian Savanna with low altitude. The experiment was conducted in Selviria, MS, Brazil, in a clayey Oxisol. The treatments consisted of four doses of K2O (0, 40, 80 and 120 kg ha(-1)), applied at sowing, and two sources: potassium chloride and potassium chloride coated by polymers. A randomized block design with eight treatments and four replications was used. The coated KCl is not efficient under the soil and climatic conditions studied, because it provided results similar to the conventional KCl for the K foliar content, crop components and grain yield of irrigated corn. The increment of K2O doses influenced positively the K and chlorophyll leaf contents, plant and spike insertion height and the number of rows and grains per spike. The maximum mean yield obtained was with 83.5 kg ha(-1) of K2O.

Reprodução de papagaio-verdadeiro (Amazona aestiva) em cativeiro: perfil anual de esteróides sexuais e ensaio de estímulo hormonal exógeno

Pós-graduação em Medicina Veterinária - FCAV

Liberação controlada de nutrientes e novos sistemas para avaliação de espécies químicas empregadas na fertilização

Pós-graduação em Química - IQ

Effectiveness of Milorganite® as a Repellent to Protect Ornamental and Agronomic Plants From Deer Over-Browsing

When deer populations become locally overabundant, browsing of ornamental and agronomic plants negatively affects plant establishment, survival, and productivity. Milorganite® is a slow-release, organic fertilizer produced from human sewage. We tested Milorganite® as a deer repellent on chrysanthemums (Chrysanthemums morifolium) in an urban/suburban environment, and soybeans (Gycine max) in a rural agriculture environment. Six beds of chrysanthemums at two sites were monitored for 28 to 35 days. Treatment plants received a top dressing of 104 grams of Milorganite® (1120.9 kg/ha). Milorganite® treated plants had more (P < 0.001) terminal buds and achieved greater height (P < 0.002) compared to controls at one site, however damage observed was similar at the second site. In a second experiment, 0.2-ha plots of soybeans (Glycine max) were planted on five rural properties in northeastern Georgia and monitored for ≥ 30 days. Treated areas received 269 kg/ha of Milorganite®. In 4 of 5 sites, Milorganite® delayed browsing on treated plants from 1 week to > 5 weeks post-planting. Duration of the protection appeared to be related to the difference in deer density throughout most of the study areas. Results of this study indicate Milorganite® has potential use as a deer repellent.

The Probe, Issue 206 – November 1999

Wildlife Damage Conferences: When, Where, and Why? -- Robert M. Timm, Editor, THE PROBE Booklet Review:"The Problem with Skunks!!" by Edward Kellems (34 pages, illustrated. $14.95) New NWCO Web Page url is http://www.wildlifedamagecontrol.com/nwcoa.htm Abstracts from the 2nd International Wildlife Management Congress, Hungary Human Disturbance as a Design Factor to Aid Displacement of Canada Geese from Urban Parks -- P. C. Whitford, Biology Department, Capital University, Columbus, OH Leopard Problems in Nepal -- T. M. Maskey, National Parks and Wildlife Conservation Department, Kathmandu, Nepal Elk-human Conflict Management in Banff National Park, Alberta, Canada -- J. A. McKenzie, Banff National Park Wildlife Laboratory The Avoidance of Virtual Barriers by Wolves in Captivity -- M. Musiani*, E. Visalberghi*, andL. Boitani, *CNR Psychology Institute, Rome, Italy Successful Field Trials of a New Slow-Release Capsaicin-Based Animal Repellent for Reducing a Variety of Human-Wildlife Conflicts in Israel -- S. C. Nemtzov, Dept. of Terrestrial Ecology, The Nature and National Parks Protection Authority, Jerusalem, Israel Educational Workshops: A Proactive Approach to Conflict Resolution in Wildlife Management -- K. B. Reis, H. R. Campa III, R. B. Peyton, and S. Winterstein, Dept. of Fisheries & Wildlife, Michigan State University, East Lansing, MI Traps and Trapping in Sweden -- T. Svensson, Swedish Environmental Protection Agency, Stockholm, Sweden Actual Problems of Predator Management in Hungary -- L. Szemethy, M. Heltai, and Z. Biro, Dept. of Wildlife Biology & Management, Godollo University of Agricultural Sciences, Godollo, Hungary Crop and Livestock Depredation by Wildlife -- N. Udaya Sekhar, Centre for Int'I. Environment & Development Studies, Aas, Norway Conservation of the Iberian Wolf in Portugal—The Everlasting Conflict with Man -- J. V. Vingada*, C. Eira, S. Scheich, C. Fonseca, M. Soares, F. L. Correia, M. Fana* P. Carmo, A. Ferreira, A. Soares, and B. Bobek. *Dept. deBiologia da Universidade do Minho, Campus de Gualtar, Portugal Barkpeeling Damage in Relation to Red Deer Density and Forest Structure in Austria -- F. H. Voelk, Institute of Wildlife Biology & Game Management, Universitaetfuer Bodenkultur Wien, Vienna, Austria Human-Wildlife Conflict Resolution: National Imperatives and Strategies -- P. 0. Wander a Kenya Wildlife Service, Nairobi, Kenya An Overview and Evaluation of Deer Herd Management Programs in Urban and Suburban Communities of the USA -- R. J. Warren, Warnell School of Forest Resources, Univ. of Georgia, Athens, GA

Applying the National Institute for Clinical Excellence criteria to patients treated with the Genous (TM) Bio-engineered R stent (TM): a sub-study of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry

The National Institute for Clinical Excellence (NICE) guidelines recommend the use of bare-metal stents (BMS) in non-complex lesions with a low risk of restenosis (diameter a parts per thousand yen3 mm and lesion length a parts per thousand currency sign15 mm) and the use of drug-eluting stents (DES) in more complex lesions with a high risk of restenosis (diameter < 3.0 mm or lesion length > 15 mm). However, the guidelines were created based on studies evaluating BMS and DES only. We performed an analysis of patients undergoing non-urgent percutaneous coronary intervention with the novel endothelial cell capturing stent (ECS). The ECS is coated with CD34(+) antibodies that attract circulating endothelial progenitor cells to the stent surface, thereby accelerating the endothelialization of the stented area. We analyzed all patients enrolled in the worldwide e-HEALING registry that met the NICE criteria for either low-risk or high-risk lesions and were treated with a parts per thousand yen1 ECS. The main study outcome was target vessel failure (TVF) at 12-month follow-up, defined as the composite of cardiac death or MI and target vessel revascularization (TVR). A total of 4,241 patients were assessed in the current analysis. At 12-month follow-up, TVF occurred in 7.0% of the patients with low-risk lesions and in 8.8% of the patients with high-risk lesions (p = 0.045). When evaluating the diabetic patients versus the non-diabetic patients per risk group, no significant differences were found in TVF, MI or TVR in either risk group. The ECS shows good clinical outcomes in lesions carrying either a high or a low risk of restenosis according to the NICE guidelines with comparable rates of cardiac death, myocardial infarction, and stent thrombosis. The TVF rate with ECS was slightly higher in patients with high-risk lesions, driven by higher clinically driven TLR. The risk of restenosis with ECS in patients carrying high-risk lesions needs to be carefully considered relative to other risks associated with DES. Furthermore, the presence of diabetes mellitus did not influence the incidence of TVF in either risk group.

Bioremediation of PAHs - Limitations and soultions

Introduction 1.1 Occurrence of polycyclic aromatic hydrocarbons (PAH) in the environment Worldwide industrial and agricultural developments have released a large number of natural and synthetic hazardous compounds into the environment due to careless waste disposal, illegal waste dumping and accidental spills. As a result, there are numerous sites in the world that require cleanup of soils and groundwater. Polycyclic aromatic hydrocarbons (PAHs) are one of the major groups of these contaminants (Da Silva et al., 2003). PAHs constitute a diverse class of organic compounds consisting of two or more aromatic rings with various structural configurations (Prabhu and Phale, 2003). Being a derivative of benzene, PAHs are thermodynamically stable. In addition, these chemicals tend to adhere to particle surfaces, such as soils, because of their low water solubility and strong hydrophobicity, and this results in greater persistence under natural conditions. This persistence coupled with their potential carcinogenicity makes PAHs problematic environmental contaminants (Cerniglia, 1992; Sutherland, 1992). PAHs are widely found in high concentrations at many industrial sites, particularly those associated with petroleum, gas production and wood preserving industries (Wilson and Jones, 1993). 1.2 Remediation technologies Conventional techniques used for the remediation of soil polluted with organic contaminants include excavation of the contaminated soil and disposal to a landfill or capping - containment - of the contaminated areas of a site. These methods have some drawbacks. The first method simply moves the contamination elsewhere and may create significant risks in the excavation, handling and transport of hazardous material. Additionally, it is very difficult and increasingly expensive to find new landfill sites for the final disposal of the material. The cap and containment method is only an interim solution since the contamination remains on site, requiring monitoring and maintenance of the isolation barriers long into the future, with all the associated costs and potential liability. A better approach than these traditional methods is to completely destroy the pollutants, if possible, or transform them into harmless substances. Some technologies that have been used are high-temperature incineration and various types of chemical decomposition (for example, base-catalyzed dechlorination, UV oxidation). However, these methods have significant disadvantages, principally their technological complexity, high cost , and the lack of public acceptance. Bioremediation, on the contrast, is a promising option for the complete removal and destruction of contaminants. 1.3 Bioremediation of PAH contaminated soil & groundwater Bioremediation is the use of living organisms, primarily microorganisms, to degrade or detoxify hazardous wastes into harmless substances such as carbon dioxide, water and cell biomass Most PAHs are biodegradable unter natural conditions (Da Silva et al., 2003; Meysami and Baheri, 2003) and bioremediation for cleanup of PAH wastes has been extensively studied at both laboratory and commercial levels- It has been implemented at a number of contaminated sites, including the cleanup of the Exxon Valdez oil spill in Prince William Sound, Alaska in 1989, the Mega Borg spill off the Texas coast in 1990 and the Burgan Oil Field, Kuwait in 1994 (Purwaningsih, 2002). Different strategies for PAH bioremediation, such as in situ , ex situ or on site bioremediation were developed in recent years. In situ bioremediation is a technique that is applied to soil and groundwater at the site without removing the contaminated soil or groundwater, based on the provision of optimum conditions for microbiological contaminant breakdown.. Ex situ bioremediation of PAHs, on the other hand, is a technique applied to soil and groundwater which has been removed from the site via excavation (soil) or pumping (water). Hazardous contaminants are converted in controlled bioreactors into harmless compounds in an efficient manner. 1.4 Bioavailability of PAH in the subsurface Frequently, PAH contamination in the environment is occurs as contaminants that are sorbed onto soilparticles rather than in phase (NAPL, non aqueous phase liquids). It is known that the biodegradation rate of most PAHs sorbed onto soil is far lower than rates measured in solution cultures of microorganisms with pure solid pollutants (Alexander and Scow, 1989; Hamaker, 1972). It is generally believed that only that fraction of PAHs dissolved in the solution can be metabolized by microorganisms in soil. The amount of contaminant that can be readily taken up and degraded by microorganisms is defined as bioavailability (Bosma et al., 1997; Maier, 2000). Two phenomena have been suggested to cause the low bioavailability of PAHs in soil (Danielsson, 2000). The first one is strong adsorption of the contaminants to the soil constituents which then leads to very slow release rates of contaminants to the aqueous phase. Sorption is often well correlated with soil organic matter content (Means, 1980) and significantly reduces biodegradation (Manilal and Alexander, 1991). The second phenomenon is slow mass transfer of pollutants, such as pore diffusion in the soil aggregates or diffusion in the organic matter in the soil. The complex set of these physical, chemical and biological processes is schematically illustrated in Figure 1. As shown in Figure 1, biodegradation processes are taking place in the soil solution while diffusion processes occur in the narrow pores in and between soil aggregates (Danielsson, 2000). Seemingly contradictory studies can be found in the literature that indicate the rate and final extent of metabolism may be either lower or higher for sorbed PAHs by soil than those for pure PAHs (Van Loosdrecht et al., 1990). These contrasting results demonstrate that the bioavailability of organic contaminants sorbed onto soil is far from being well understood. Besides bioavailability, there are several other factors influencing the rate and extent of biodegradation of PAHs in soil including microbial population characteristics, physical and chemical properties of PAHs and environmental factors (temperature, moisture, pH, degree of contamination). Figure 1: Schematic diagram showing possible rate-limiting processes during bioremediation of hydrophobic organic contaminants in a contaminated soil-water system (not to scale) (Danielsson, 2000). 1.5 Increasing the bioavailability of PAH in soil Attempts to improve the biodegradation of PAHs in soil by increasing their bioavailability include the use of surfactants , solvents or solubility enhancers.. However, introduction of synthetic surfactant may result in the addition of one more pollutant. (Wang and Brusseau, 1993).A study conducted by Mulder et al. showed that the introduction of hydropropyl-ß-cyclodextrin (HPCD), a well-known PAH solubility enhancer, significantly increased the solubilization of PAHs although it did not improve the biodegradation rate of PAHs (Mulder et al., 1998), indicating that further research is required in order to develop a feasible and efficient remediation method. Enhancing the extent of PAHs mass transfer from the soil phase to the liquid might prove an efficient and environmentally low-risk alternative way of addressing the problem of slow PAH biodegradation in soil.

Kontrollierte Fällung von amorphem Calciumcarbonat durch homogene Carbonatfreisetzung

In der Vergangenheit haben Untersuchung an biologischen und Modell-Systemen gezeigt, dass amorphes Calciumcarbonat als instabiles Zwischenprodukt bei der Bildung kristalliner Strukturen aus CaCO3 auftritt. Über dessen Rolle im Fällungsprozess von CaCO3 ist nicht viel bekannt und es wird davon ausgegangen, dass es als CaCO3-Speicher für die nachfolgenden kristallinen Produkte dient. Der genaue Reaktionsablauf, der zur Bildung von amorphem Calciumcarbonat (ACC) führt, ist nicht bekannt. Ziel dieser Arbeit war die Entwicklung einer Fällungstechnik, die die Beobachtung der Bildungskinetik von ACC durch Lichtstreuung ermöglicht. In Fällungsexperimenten wird gezeigt, dass die Fällung unter nicht-turbulenten Bedingungen zur Bildung von amorphem Calciumcarbonat führt. Hinsichtlich der Basen- und Alkylcarbonatmenge, die äquivalent oder im Überschuss zur Calciumionenkonzentration eingesetzt wird, entstehen zwei verschiedene Fällungsprodukte. In Bezug auf ihre chemische Zusammensetzung, thermische und mechanische Eigenschaften werden diese charakterisiert. In beiden Fällen wird ein amorphes CaCO3 mit einem Wassergehalt von 0,5 mol/L pro Mol CaCO3 erhalten. Die in situ Generierung von Carbonat führt zur Bildung von sphärischem amorphem Calciumcarbonat, das eine gewisse Tendenz zur Koazervation zeigt. Die bei gleichem Reaktionsumsatz beobachtete Temperaturabhängigkeit des Partikelradius konnten wir unter Annahme einer Mischungslücke mit unterer kritischer Mischungstemperatur interpretieren. Für die Bildung von amorphem Calciumcarbonat schlagen wir daher einen Mechanismus via binodaler flüssig-flüssig Entmischung vor. Nach einer kurzen Keimbildungsperiode können flüssige Tröpfchen aus wasserhaltigem CaCO3 wachsen und dann infolge von stetigem Wasserverlust glasartig erstarren und so amorphes Calciumcarbonat bilden. Bekräftigt wird dieses Modell durch die Wachstumskinetik, die mittels Lichtstreuung und SAXS verfolgt worden ist. In den Fällungsversuchen sind je nach Reaktionsbedingungen, zwei verschiedene Zeitgesetze des Teilchenwachstums erkennbar: Bei schneller Freisetzung von Carbonat liegt ein parabolischer Verlauf des Radienwachstums vor; hingegen führt eine langsame Freisetzung von Carbonat zu einem linearen Wachstum der Radien. Diese Abhängigkeiten lassen sich im Rahmen der bekannten Kinetik einer flüssig-flüssig Entmischung deuten. Ferner wird der Einfluss von doppelthydrophilen Blockcopolymeren (PEO-PMAA) auf die Teilchengröße und die Kinetik der Bildung von amorphem Calciumcarbonat untersucht. Zum Einsatz kommen zwei verschiedene Blockcopolymere, die sich in der Länge des PEO-Blocks unterscheiden. Im Fällungsexperiment führt das in sehr kleinen Konzentrationen vorliegende Blockcopolymere zur Stabilisierung von kleineren Partikeln. Das Blockcopolymer mit der längeren PEO-Einheit weist eine größere Effizienz auf. Die Ergebnisse lassen sich durch Annahme von Adsorption des Polymers an der Oberfläche interpretieren. Der Einfluss der doppelthydrophilen Blockcopolymere auf die Bildung von ACC deutet darauf, dass amorphes Calciumcarbonat eine komplexere Rolle als lediglich die eines Calciumcarbonatspeichers für das spätere Wachstum kristalliner Produkte einnimmt. Für die Wirkung von Polymerzusätzen muss somit nicht nur die Wechselwirkung mit den gegen Ende gebildeten Kristalle betrachtet werden, sondern auch der Einfluss, den das Polymer auf die Bildung des amorphen Calciumcarbonats hat. Die hier neu entwickelte Methode bietet die Möglichkeit, auch für komplexere Polymere, wie z.B. extrahierte Proteine, den Einfluss auf die Bildung der amorphen Vorstufe zu untersuchen.

Enteric coated mucoadhesive micropellets in rotary agglomeration process for wet spheronization

In this work a generally applicable method for the preparation of mucoadhesive micropellets of 250 to 600µm diameter is presented using rotor processing without the use of electrolytes. The mucoadhesive micropellets were developed to combine the advantages of mucoadhesion and microparticles. It was possible to produce mucoadhesive micropellets based on different mucoadhesive polymers Na-CMC, Na-alginate and chitosan. These micropellets are characterized by a lower friability (6 to 17%) when compared to industrial produced cellulose pellets (Cellets®) (41.5%). They show great tapped density and can be manufactured at high yields. The most influencing variables of the process are the water content at the of the end spraying period, determined by the liquid binder amount, the spraying rate, the inlet air temperature, the airflow and the humidity of the inlet air and the addition of the liquid binder, determined by the spraying rate, the rotor speed and the type of rotor disc. In a subsequent step a fluidized bed coating process was developed. It was possible to manifest a stable process in the Hüttlin Mycrolab® in contrast to the Mini-Glatt® apparatus. To reach enteric resistance, a 70% coating for Na-CMC micropellets, an 85% for chitosan micropellets and a 140% for Na-alginate micropellets, based on the amount of the starting micropellets, was necessary. Comparative dissolution experiments of the mucoadhesive micropellets were performed using the paddle apparatus with and without a sieve inlay, the basket apparatus, the reciprocating cylinder and flow-through cell. The paddle apparatus and the modified flow-through cell method turned out to be successful methods for the dissolution of mucoadhesive micropellets. All dissolution profiles showed an initial burst release followed by a slow release due to diffusion control. Depending on the method, the dissolution profiles changed from immediate release to slow release. The dissolution rate in the paddle apparatus was mainly influenced by the agitation rate whereas the flow-through cell pattern was mainly influenced by the particle size. Also, the logP and the HLB values of different emulsifiers were correlated to transfer HLB values of excipients into logP values and logP values of API´s into HLB values. These experiments did not show promising results. Finally, it was shown that manufacture of mucoadhesive micropellets is successful resulting in product being characterized by enteric resistency combined with high yields and convincing morphology.

Leukocyte- and Platelet-Rich Fibrin (L-PRF) for Long-Term Delivery of Growth Factor in Rotator Cuff Repair: Review, Preliminary Results and Future Directions

Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.