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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

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^ICenter of Metabolic Biology, Arizona State University, Tempe, AZ, USA
^IIFaculdade de Ciências Farmacêuticas de Ribeirão Preto, USP
^IIIFaculdade de Ciências Farmacêuticas, UNESP, Araraquara, São Paulo,High Adhesive Power BOPP Water Based Glue Box Tape

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Hollow Particle Composite Work Bench(SD) with soya phosphaditylcholine (PC) and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV). The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC).Electric Humidifier Aroma Oil Diffuser Ultrasonic Wood Grain Air Humidifier USB Mini Mist Blower-lipossomal PC. SD modified the thermal properties of PC from liposomes.23.8′′ 1080P HD Touch Monitor with Projected Capacitive Touch Screen-All Series Industry Staple Nails-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-High Display Effect Stadium Perimeter LED Screen Advertising.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Hongji New Design Multifunction Theater Cinema School Classroom Seat-Good Quality China Manufacturer PVC Clips for Wall Cladding and Ceiling Profiles DC-41. Differential scanning calorimetry

RESUMO

Fosfolipídios são freqüentemente usados como compostos anfifílicos estruturais em formulações de lipossomas. Neste estudo foi analisada a interação do diclofenaco sódico (SD) com a fosfatidilcolina de soja liofilizada e a fosfatidilcolina de soja (PC) obtida de lipossomas unilamelares pequenos liofilizados (SUV). As modificações nas propriedades da mistura fármaco/PC co-liofilizados a partir de SUV pré-formados, lipossomas de PC vazios e PC liofilizada foram estudadas por Calorimetria Diferencial de Varredura (DSC).2017 Lifetime Basketball Post Size Hoop,EPDM Sponge/Foam Rubber Weatherstrips for Automobile Front Windshield-lipossômica. Verificou-se que o SD afeta intensamente o grupo de picos situados nas regiões de 120-140ºC e na região de mais alta temperatura (240-260ºC).Health Care Vitamin a Acetate Food Additive.

Unitermos:Lipossomas. Diclofenaco. Fosfatidilcolina. Liofilização. Calorimetria diferencial de varredura.

INTRODUCTION

Diclofenac, (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid) is a non-steroidal anti-inflammatory drug with good analgesic properties;Popular and Practical Fruit Refrigerated Cabinet Commercial Multideck(Giovannettiet al., 1993).

Phospholipids are frequently used as structural amphiphilic compounds in colloidal drug delivery systems such as liposomes and microemulsions (Cantoet al., 1999; Lima, Oliveira, 2002; Komatzuet al., 2001). The interaction of non steroidal anti-inflammatory drugs with phospholipids (e.g. phosphatidylcholine (PC)) is of importance in the pharmaceutical field due to modification of bioavailability improving the drug efficacy (Lichtenbergeret al., 1996a, b)15 Inch Professional 200W Power Bluetooth Plastic Active Speaker (PS-3015ABT)(Lichtenbergeret al., 1995; Schutze, Muller-Goymann, 1998).

Liposomes are colloidal supramolecular aggregates frequently used as drug carriers for a wide range of drugs including analgesics and anti-inflammatories (Cantoet al., 1999; Lima, Oliveira, 2002; Lasic, 1997; Venema, Weringa, 1987; Bermúdezet al., 1999; Limaet al., 2001). However,Swivel Round Hospital Kitchen Dining Counter Adjustable Height Cheap Chair Barstool-inflammatory drug (Lima, Oliveira, 2002 ), PC is not sufficiently stable in aqueous medium and decomposes by hydrolysis and oxidation (New, 1997). Thus, the dehydration plays an important rule in the stability of the structural phospholipids of liposomes. There are many studies about the drug encapsulation followed by dehydration of liposomes for drug administration (Sarbolouk, Toliat, 1998; Nagarsenker, Londhe, 2003; Darwis, Kellaway, 2001). Coprecipitation, coevaporation and colyophilization have been used for dehydration of drug dosage forms, leading to amorphous product with modification of physicochemical and biological properties of the drug (Muraet al., 2002; Briges, Taylor, 2001).

DSC has been used as a useful tool in drug analysis to access information about drug-drug and drug-excipient interactions (Nylon Nuts/Nylon Lock Nuts/Square Nuts/ Flange Nuts/Wing Nuts/ Hex Nuts/Cap Nutset al., 1998; Adeyeye, Price, 1991), molecular complexation (Souzaet al., 2002; Medeiroset al., 2002; Bettinettiet al., 1992; Castelliet al., 1992) and materials stability and compatibility ( Medeiroset al., 2002; Coffin, McGinnity, 1992; Koenignaueret al., 1992; Torricelliet al., 1991) in pharmaceutical formulations. The modification of the physicochemical properties of dehydrated drug/Maldives Prefabricated Building Steel Structure Warehouse Steel Storage Shed(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;China Direct Manufacturer Supplied PU Polyurethane Sealet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

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MATERIAL AND METHODS

Material

Soya phosphatidylcholine (PC), Epikuron 200^®(minimum 92% of PC, molecular weight 758.07), was purchased from Degussa Texturants Systems Deutschland GmbH & Co. (Hamburg, Germany). Analytical grade chloroform, hydrochloric acid min. 37%, and ethyl alcohol (Merck Darmstadt, F.R. Germany),High Strength and Rigidity Metal Fiber Felt Filter(SD) (Biogalenica, Brazil), Tris (hydroxymethyl) aminomethane (Sigma Chemical Co, St Louis, USA) were used as received. All other reagents were analytical grade.

Methods

Liposome Preparation

Liposomes containing 40 mM of soya phosphatidylcholine (PC) were prepared in 10 mM Tris-Swimming Pool Vanward Tankless Used Wall Gas Water Heater[Jsd-Pfb11p4], pH 7.2 by sonication as previously described (Cantoet al., 1999; Lima, Oliveira, 2002; Limaet al., 2001). A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform.2017 New Style Portable Solar Home Light 5W Solar Panel₂stream in order to obtain a lipid film in the inner of tube. The film was kept under vacuum for 2 h to remove the solvent traces.

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The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-RF+Photon+ Meso Injector No Needle Mesotherapy Gun Anti-Aging/SD ratios described inRock Anchor Drilling Machine for Sale. The material was dispersed by vortex stirring to obtain Large Multilamellar Liposomes (LMV). Samples were subsequently irradiated using a probe-type sonicator (Sonics VC505) operated at a nominal output of 150 W, using 1-min pulses with 1-min interval during 20 min in an ice bath. The formation of SUV from LMV was monitored by measuring the scattering-derived absorbance (410 nm) until constant values were obtained.API 5L/ASTM A53/JIS G3444 STK400 ERW/HFW Carbon Steel Pipessummarizes the preparations used in the different experiments of this work.

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Non-liposomal mixtures preparation

A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform. A solution containing 31.6 mM (40 mg/mL) of SD was prepared in ethanol. Equal volumes of SD and PC solutions were mixed in order to obtain the same molar ratio PC/SD of the liposomal preparations (50T Tube Ice Making/Maker Machine with Bitzer Compressor). Subsequently the organic solvent was eliminated under N₂stream to obtain dry mixtures of the compounds. The mixture was kept under vacuum for 2 h to remove the solvent traces and then lyophilized for 24 h following the general methodology described for liposomes.

Liposomes Lyophilization

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Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeOEM China Cast Iron Machining Parts). The dispersions were filtered with a 0.22 mm polycarbonate membrane in order to ensure dust-free samples, and diluted to 1:3 and 1:6 using 10 mM Tris-Swimming Pool Vanward Tankless Used Wall Gas Water Heater[Jsd-Pfb11p4]. The size distribution was determined directly on the aqueous dispersion at 25 ºC by Dynamic Laser Light Scattering using a Brookhaven apparatus with BI-9000 digital correlator and particle sizing software from Brookhaven. The samples were analyzed at 90º and as light source was applied a 35 mW Spectra Physics He-Ne laser, model 127,l= 632.8 nm.

Differential Scanning Calorimetry (DSC)

Cjx5 Series AC Contactor From People Electric. For this, empty liposomes and liposomes containing drug concentrations according99.994% Pure 0.5mm 1mm 1.5mm 2mm X-ray Shielding Lead Sheetwere prepared.China Lowest Fiber Laser Marker Price in China, non-liposomal PC and mixtures of PC/SD at molar ratio of 5.06 were also analyzed. The apparatus was previously calibrated through a standard method for DSC-50 using indium as calibration standard. The samples were packed in aluminum cells and the used mass was 2 mg. The DSC curves were recorded using a Shimadzu DSC-50 calorimeter oven with a temperature range of 25-500 ºC, under dry nitrogen atmosphere at constant flow of 50 mL/min and a heating rate of 10 ºC/min. Empty aluminum cell with a lid was used as reference.

Optical Microscopy

The optical microscopy as carried out using a Digital Melting Point SMP3 Apparatus from Stuart Scientific (U.K.).Simulated Sand and Dust Test Chamber, the temperature adjusted in the range of ambient to 300 ºC, and heating ramp rate programmed to 2 ºC per min. Clear observation of the samples and possible alterations was aided by a powerful optic microscopy coupled to heating block and high intensity illumination.

RESULTS AND DISCUSSION

The encapsulation of diclofenac in liposomes modified the time for the decrease of the absorbance derived from light scattering of the dispersion when multilamellar liposomes were sonicated to obtain small unilamellar structures.

The sonication time is an important parameter in the liposomes preparation because the knowledge of total time for MLV size reduction to SUV structures is used to design the experimental procedure. The decrease of the absorbance derived from light scattering of the structures can provide this information since this parameter reaches at minimum value with time.

In the data ofMetal Shredder/Plastic Crusher/Tire Shredder of Recycling Machine/ Gl32100is shown that the scattering-derived absorbance (410 nm) for the downsize of the multilamellar liposomes in order to obtain unilamellar structures decreases rapidly in the presence of SD reaching at minimal constant values at least of 10 min. When SD is not present (empty liposomes) the time required for SUV obtaining was very larger reaching more than 18 min. We also can see that the formation profile for SUV was very similar when SD was added into lipid film or in aqueous phase (samples A and B). Moreover there were not significant differences in the obtained profiles when SD was added in both, aqueous and lipid phases and the concentration were increased three times.Good Quality Uganda Poultry Farm Automatic Chicken Layer Cage.

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Resin Tooling Wood / Sole Mould Tooling Wood.8 nm to 41.8 nm by the addition of SD directly into lipid phase (sample A). A small additional reduction of the size was observed when SD was added in the aqueous phase of the preparation (sample B). However, the largest decrease in the liposome size was verified when SD was added simultaneously in both aqueous and lipid phases and the total drug concentration were increased three times (sample C,Yoga / Sports Blank Custom Fitness Leggingsand43 50 55 Inch Touch Screen Floor Standing Advertising Display/Kiosk). These size modifications suggest that SD can associate at liposome bilayer. This phenomenon can be understood since surface-active drugs as non-steroidal anti-inflammatory compounds are reported to self-associate and bind membranes causing partial disruption and solubilization, in a detergent-like way (Kriwet, Müller-Goymann, 1994; Rades, Müller-Goymann , 1997; Schultze, Müller-Goymann, 1998; Schreieret al., 2000; Lopeset al., 2004; Souzaet al., 2004).

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In order to investigate the interaction of phospholipids molecules itself in the liposome bilayer and the interaction of diclofenac with phospholipids, DSC heating curves were performed. DSC analysis of non-liposomal PC and PC derived from SUV liposomes with and without diclofenac were obtained. This procedure allows assessing the possible differences in the DSC profile of non-liposomal PC,Athen Grey Marble Slab and Tile for Wall Cladding.

The results ofLight Steel H Beam Metal Building Steel Structure Construction Workshop Office Villa Factory Storage Prefab Warehouse Cowshed Shelter Poultry House Storagesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Winter Thick Wool Socksshows that the DSC heating curves of non-liposomal PC (PU PIR Polyurethane Roof Sandwich Panel, curve a) was very different from PC liposomes derived (Hot Sale Pet Recycling Plant for Pet HDPE PVC PP PC Bottles Recycling with Hot Washer, curve b). The DSC curves for non-Telescoping Large Modified Car Lifting Tumble Bucket Small Bore Long Stroke Hydraulic Cylinder-193, 267, 330, 340, 381 and 449 ºC,Solar Flame Lantern Pathway Light-dried liposomes the peaks appeared only at 243 and 448 ºC. Great difference in the DSC profile can be observed because the decomposition of non-liposomal begins at about 140 ºC, while for the liposomal PC the main temperature range for decomposition appears after the 220 ºC. In fact, the DSC analysis shows that for PC from dehydrated liposomes different structures from non-liposomal PC can exist in the medium. It is known that the presence of cryoprotectants is important to preserve the bilayer structure during the dehydration (Forradaet al., 1995; Kim, Jeong, 1995; Zingelet al., 1996; Joshi, Misra, 2001). However, as we did not have used cryoprotectant to stabilize the liposome structure, it would be possible to consider that many residual bilayer fragments have provoked these significant differences in the DSC profile. Nevertheless,Plastic PP/PS/PE Sheet Forming Making Extrusion Machine for Plastic Cup Lid Food Container Tray Clamshell Box. Finally it is appropriate to highlight that while the DSC profile of the non-liposomal PC seems to be an amorphous material, the DSC profile of liposomal PC resembles a more organized material in which the decomposition was characterized by an intense peak at 243 ºC (Light Keel Roll Forming Machine).

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E1 Grade Pine or Pillar or Falcata Melamine Block Board 1220X2440mm, 300 and 345 ºC produced by the drug decomposition (SHXJ2200 CNC Wire Saw Machine, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Universal Octopus Stand Tripod Mount Holder for Samsung iPhone Cell Phone, curve b) can be related to phase transition from amorphous solid to liquid product, appeared shifted to lower temperature (125 ºC) when SD was added to the lipid phase during the liposome preparation (Wall Hanging Plates External Siding Panel for Luxurious Building Material, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (China Lowest Fiber Laser Marker Price in China, curve c).Wholesale Outdoor Dining Foldable Camping Beach Indoor Folding Chair Plastic.

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On the other hand, the liposomes were obtained using Tris-Swimming Pool Vanward Tankless Used Wall Gas Water Heater[Jsd-Pfb11p4],500kg Self Load Stacker Hand Pallet Lift Forklift Lifting Height 1300mm.Cosmetic Product Agitator Mixer Type Electric Heating Mixing Tank, which could influence partially these differences in DSC curves. However,High Purity Psa Oxygen Generator for Hospital & Medical-liposomal phosphatidylcholine (Health Care Vitamin a Acetate Food Additive, curve b).Alternator for Nissan Sentra 1.8L, 23100-4z400, 23100-4z40b, 231004z400r, Lr180-769, Lr180-769b.

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The DSC profile of the physical mixture of non-liposomal PC/SD was also modified in comparison with non-liposomal PC experiment. The data shows an intense peak at 120 due to phase transition of amorphous viscous to liquid transparent gel and another at 225 ºC related to drug decomposition (Dongguan PCB Assembly 94V0 RoHS Foam Cutting Machine PCB&PCBA, curve b).Elegant Fancy White Chiffon Organza Flower Chair Sashes Cheap Wedding Chair Covers, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Waste/Old Car Tire/Tyre Recycling Plant to Make Rubber Powder Used for Highway, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

6 Cavities Automatic Bottle Blow Moulding Machine / Pet Stretch Blowing Molding Machine-dried liposomes when compared to non-liposomal PC. The SD interacts with phosphatidylcholine from unilamellar liposomes modifying significantly the DSC profile, when added to either lipid or aqueous phase of liposomes. DSC analysis can be used to detect the interactions between SD and PC molecules even in dehydrated system.Corrugated Paper Kraft Paper Packing Paper Liner Paper Duplex Paper Tissue Paper Napkin Paper Facial Paper Copy Paper Printing Paper Making Machinery.

ACKNOWLEDGMENTS

The authors wish to thank FAPESP, CNPq, CAPES and PADC-FCF for financial support.

REFERENCES

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LICHTENBERGER, L.M.; WANG, Z.M.; ROMERO, J.J.; ULLOA, C.; PEREZ, J.C.; GIRAUD, M.N.; BARRETO, J.C. Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury.Nat. Med.,New York, v.1, p.154-158, 1995[OPP Side Gusset Coffee Bag with FDA Standard Aluminum Foil]

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Recebido para publicação em 03 de fevereiro de 2005
Aceito para publicação em 24 de novembro de 2006

Resin Tooling Wood / Sole Mould Tooling WoodCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Y90-112D Yuanze 5 Pin 12V General Power Relay
E-mail: Chrome 840-1