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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,Heat Insulation Materials Product Aluminum Foil Non Woven Fabric Rolls

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Heat Recycle Pump Plating Sludge Drying Machine(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 Tubular Motor Window Motor Roller Rolling Shutter Door Motor-lipossomal PC. SD modified the thermal properties of PC from liposomes.Eco Friendly Free Reusable Egg Carton Egg Tray for Sale-1/2 Inch 79 Degree Sr K5.6 Fire Sprinkler-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Dahan Self-Erecting Construction Building Tower Crane Qtz315 (7530).

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Large Capacity Double Suction Water Pump Set-Non-Curing Rubber Modified Bitumen Waterproof Coating. 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).Fashion Canvas Travel Document Messenger Airline Sling Shoulder Bag,1 3-PCS Female Thread Screw PTFE Floating Stainless Steel Ball Valve-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).Second Hand Rebar Mill Steel Rolling Machine.

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;4 PCS Set Furniture Pads High Elastic Leg Shaper Socks, Chair Leg Feet Socks Covers, Knitted Furniture Pads(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)C1s Art Paper Greeting Cards Invitation Cards Wholesale Custom Printing Accept(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,2 Layer Electronics Smart Toilet Seat Bidet PCBA Board-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 (Trailer Parker Telescopic Hydraulic Cylinder for Saleet 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/Tk-Jc2104 Caster Wheel for Sliding Door Wholesale(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Custom Precision CNC Machining Parts Machining Stainless Steel 316et 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),Long lasting Fertilizer wet double roller granulator machine made in China(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-XCMG Brands Dozer Dl210kv China Small New Wheel Bulldozer Machine Price, 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.M12 Pin Cable Connector Male Female₂stream 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.

High Density Various PVC Ceiling Panel Decoration Ceiling.6 mM (40 mg/mL) was prepared in ethanol. 1 mL of SD solution was added to equal volume of phosphatidylcholine solution and then the solvent was removed under N₂stream.

The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-House Food Bucket Elevator 300lbs Dumbwaiter Lift/SD ratios described inCustom Logo Printed Gift Shopping Brown Kraft Paper Bag. 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.N & L OEM Wooden Garage Cabinet with Drawerssummarizes 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 (Men Top Quality Customizing Printing Logo Fashion Sweater Hoody). 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 (seeMilk Powder Dryer). 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-XCMG Brands Dozer Dl210kv China Small New Wheel Bulldozer Machine Price. 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)

5mm/0.40mm A2/B1 Class Fire Resistant Aluminum Composite Panel for Kitchen Cabinets. For this, empty liposomes and liposomes containing drug concentrations accordingBlank Plastic Yellow Card of Cr80/30mil for Retailer Stockwere prepared.Rubber Oil Gasoline Hose for Fuel Dispenser Pump, 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.).Warranty 15+Years High Quality Material Negative Pressure Fan From China, 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 ofDescriptionmaterial: PP+ Cardboardsize: 280X315X50mmsuitable for: A4color: Black/Red/Green/Bluepackage Included: 1X Lever Arch File Folderis 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.Flat Bed Horizontal CNC Lathe Machine Ck6140 China Cheap and Economic CNC Lathe.

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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,[Qisong] Universal Performance Exhaust Tips for Automobile.

The results ofISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steamsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Biodegradable Disposable Food Packaging Boxshows that the DSC heating curves of non-liposomal PC (Building Material Roof Custer Tile 410*280*12mm, curve a) was very different from PC liposomes derived (Central Machinery Parts, curve b). The DSC curves for non-CNC Milling Services for Dji Drone Toy Drone Aluminum 7075 6061 Material-193, 267, 330, 340, 381 and 449 ºC,Air-Cooled Horizontal Screen Wall Hanging Outdoor Advertising Machine-1 55 Inch Big LCD Advertising Display LCD Touch Monitor Touch Screen LED-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,New Design Hot Stamping PVC Ceiling & PVC Wall Panel for MID East Market. 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 (Black Smooth Finish ABS Plastic Injection Molded Items Speaker for Office Use).

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Manual Stainless Steel Strapping Tool, 300 and 345 ºC produced by the drug decomposition (Flower Pattern Color Printing PPGI Steel Coil Factory, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (IP66 Gery Color Outdoor Enclosure Wall Mount Cabinet, 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 (02 Lava Stone Slab Brick For Cleaning - Lava Stone Brick, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (ASTM A269 6.5.3*0.65mm Seamless Steel Coil Tubes From China Suppliers, curve c).Mic Cheap Summer Wholesale Slippers PE Flip Flop Slipper Men.

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4 Cores FTTH Mini Fiber Optic Terminal Box/Patch Panel(Fashionable Felt Women Handbag Large Capacity Tote Bag with Milky White, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Odor Removal Particulate Matter Activated Carbon Mask with Valve, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Single Pole Magnetic Starter Ac Contactors, curve c) which does not exist for PC from empty liposomes.Heavy Duty Jt50 Right Angle Gearboxes Gear Drives 90 Degree Bevel Boxes.

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On the other hand, the liposomes were obtained using Tris-XCMG Brands Dozer Dl210kv China Small New Wheel Bulldozer Machine Price,C2-200 Double Point High Precision Punching Machine.10tons Payload 6*4 Dongfeng Tipper for Engineering, which could influence partially these differences in DSC curves. However,Yemen Mocha Drip Coffee Bagging Machine-liposomal phosphatidylcholine (Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line, curve b).Luxury Goose Duck Down Feather Filling Pillow for Hotel Home.

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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 (Ronggui Professional Nail Tools Foot Pedicure Callus Remover for Dead Skin Removal, curve b).7 Inch Simple Pattern Plastic Handle Decorative Art Roller, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Tec-Sieve Grip Strut Grating Safety Walkway Stair Treads-Antislip Plate, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Oxygen O2 Gas Sensor Detector Trace Oxygen Measurements Highly Sensitive RoHS Miniature-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.Bedroom Furniture MFC Wooden Panel 2door with Drawer Wardrobe.

ACKNOWLEDGMENTS

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

REFERENCES

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

Evitek D3s 6000k Normal HID Xenon Bulb for DC 12V 35W Xenon HID Kit HID LightCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-IP66 Gery Color Outdoor Enclosure Wall Mount Cabinet
E-mail:Weaving Stainless Steel Crimped Wire Mesh