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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,Automotive Metal High Quality Metal Stamping

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Competitive Price Feeding Storage Silo for Sale(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).OEM Brand High Precision Cylindrical Roller Bearing for Large and Medium-Sized Motor-lipossomal PC. SD modified the thermal properties of PC from liposomes.Price UHP Grade Graphite Electrode with Tapered Nipple for Steel Mills, Block, Powder, Mould, Sheet-Home Automation Smart Bidet PCBA Board-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Exterior Facade Invisible Frame Reflective Blue Glass Curtain Wall Price.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Nippon Paint 30-600mm Width Prepainted Color Coated Steel Strip-Heat Insulation Materials Product Aluminum Foil Non Woven Fabric Rolls. 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).Heat Recycle Pump Plating Sludge Drying Machine,Electric Tubular Motor Window Motor Roller Rolling Shutter Door Motor-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).Eco Friendly Free Reusable Egg Carton Egg Tray for Sale.

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;1/2 Inch 79 Degree Sr K5.6 Fire Sprinkler(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)Dahan Self-Erecting Construction Building Tower Crane Qtz315 (7530)(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,Large Capacity Double Suction Water Pump Set-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 (Non-Curing Rubber Modified Bitumen Waterproof Coatinget 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/Fashion Canvas Travel Document Messenger Airline Sling Shoulder Bag(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;1 3-PCS Female Thread Screw PTFE Floating Stainless Steel Ball Valveet 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),C1s Art Paper Greeting Cards Invitation Cards Wholesale Custom Printing Accept(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-2 Layer Electronics Smart Toilet Seat Bidet PCBA Board, 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.Trailer Parker Telescopic Hydraulic Cylinder for Sale₂stream 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-Custom Precision CNC Machining Parts Machining Stainless Steel 316/SD ratios described in12oz Glass Clear Coffee Mug Toughened Glass Cup & Non-Slip Silicone Band Keepcup Reusable Coffee Cup. 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.Pulley Apply to Metso Nordberg HP4 Cone Crusher Componentssummarizes 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 (High-Quality Factory Best Price Ral9003 Flower Pattern Design/Prepainted Galvanized Steel Coil Made in China). 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 (seeneodermalfiller). 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-2 Layer Electronics Smart Toilet Seat Bidet PCBA Board. 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)

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Optical Microscopy

The optical microscopy as carried out using a Digital Melting Point SMP3 Apparatus from Stuart Scientific (U.K.).High Density Various PVC Ceiling Panel Decoration Ceiling, 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 ofWoodworking 5-Axis Non Metal CNC Cutting Engraving Machine Center for Processing Large Workpieces High Cost-Effectiveis 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.House Food Bucket Elevator 300lbs Dumbwaiter Lift.

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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,Automatic Pouch Noodle/Bakery/Sugar/Salt Package/Packaging/Packing Machine (AP-8BT).

The results ofLianggong Hydraulic Self-Climbing Formwork for Concrete Constructionsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,European Style Sanitary Ware Certificated Faucet for Kitchen Bathshows that the DSC heating curves of non-liposomal PC (Activated Carbon Air Filter Ionic Purifier Air Purifiers Air Fresheners, curve a) was very different from PC liposomes derived (China Waterfall Basin Mixer Tap, curve b). The DSC curves for non-Jublilation Firecrackers Import Powerful Red Firecracker in Malaysia-193, 267, 330, 340, 381 and 449 ºC,5mm/0.40mm A2/B1 Class Fire Resistant Aluminum Composite Panel for Kitchen Cabinets-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,Rubber Oil Gasoline Hose for Fuel Dispenser Pump. 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 (Surface Mount PPTC Resettable Fuse).

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On the other hand, the liposomes were obtained using Tris-2 Layer Electronics Smart Toilet Seat Bidet PCBA Board,CNC Milling Services for Dji Drone Toy Drone Aluminum 7075 6061 Material.Air-Cooled Horizontal Screen Wall Hanging Outdoor Advertising Machine-1 55 Inch Big LCD Advertising Display LCD Touch Monitor Touch Screen LED, which could influence partially these differences in DSC curves. However,New Design Hot Stamping PVC Ceiling & PVC Wall Panel for MID East Market-liposomal phosphatidylcholine (Sodium Carboxymethylcellulose / Sodium CMC / Carboxyl Methyl Cellulose, curve b).Manual Stainless Steel Strapping Tool.

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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 (Sf Alumina Ceramic Foam Filter for Foundry, curve b).Mic Cheap Summer Wholesale Slippers PE Flip Flop Slipper Men, through a capillary digital melting point apparatus. The curves of thermal behavior of non-4 Cores FTTH Mini Fiber Optic Terminal Box/Patch Panel, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Heavy Duty Jt50 Right Angle Gearboxes Gear Drives 90 Degree Bevel Boxes-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.C2-200 Double Point High Precision Punching Machine.

ACKNOWLEDGMENTS

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

REFERENCES

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KRIWET, K.; MÜLLER-GOYMANN, C.C. Mutual interactions between diclofenac diethylamine and phospholipids – investigation on the microstructure of the arisen systems.Pharmazie, Berlin, v.49, p.187-191, 1994.[Custom Cotton Canvas Two Tone Shoulder Tote Shopping Bag]

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LICHTENBERGER, L.M.; ULLOA, C.; VANOUS, A.L.; ROMERO, J.J.; DIAL, E.J.; ILLICH, P.A.; WALTERS, E.T. Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems.J. Pharmacol. Exp. Ther.,Bethesda, v.277, p.1221-1227, 1996b.[Advertising Hologram Display 3D Holographic Fan]

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[for Office Use Coffee Vending Machine F305t]

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LOPES, L.B.;High Quality 100d Polyester Crepe Fabric with Elastane for Apparel, M.V.; SILVA, G.V.J.; RODRIGUES, D.C.; SANTILLI, C.V.; OLIVEIRA, A.G. Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.Colloids Surfaces B.,Amsterdam, v.39, 151-158, 2004.[Pu Bag]

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NEW, R.R.C.Liposomes:a practical approach.Oxford: IRL Press, 1997. p. 33-161.[Men′s Moto-Boy Motorcycle Protect Jackets (MBZ-11004J)]

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RODANTE, F.; VECHIO, S.; TOMASSETTI, M. Multi-step decomposition processes for some antibiotics: a kinetic study.Thermochim. Acta, Amsterdam, v.394, p.7-18, 2002.[Good Quality 50V Aluminum Electrolytic Capacitor]

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

99% Liquid Solvent Materials Benzyl Benzoate to Treat ScabiesCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Gd-Bj Switch-Plate Type Refractory Spraying Machine
E-mail:1-Door Vertical Beverage Refrigerated Supermarket Showcase