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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,China Factory Customized Plastic Packaging Products for Electronic Parts

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Dental Supplies Surgical Tray Dental 201 Stainless Steel Medical Instrument Tray Useful Tool for Clinic Lab(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).Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIY-lipossomal PC. SD modified the thermal properties of PC from liposomes.Push Button Switch 12mm Metal Switch 12V Momentary/on-off Switch 4 Pin with LED Light Logo-Vibratory Bowl - for Polished Finish on Wheels / Alloys-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Aualified Composite White Solid Surface Dining Coffee Table.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Customized Alloy Steel Yoke Forged Metals Products-Fashionable Felt Women Handbag Large Capacity Tote Bag with Milky White. 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).280 Centigrade Fiberglass Silicone Tube/ Silicone Fiberglass Tube,2016 New Hand Push Manual Corn Seeder-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).Fashion Custom Printed Thin Silicone Wristband/Sports Team Memorial Silicone Bracelets.

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;Aluminum Wheel Polishing Machine Alloy Wheel Repair Lathe Machine for Sale Wrm28h(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)Super Absorbent Cooling Towel PVA Sports Towel(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,Rubber Vulcanizing Press and Rubber Hydraulic Press Vulcanization 90 Ton-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 (6 Mesh Plain Weave Stainless Steel Wire Meshet 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/Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Fiberglass Filtering Net for Foundryet 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),Hot Sale PC LED Tube Light Housing Batten Extrusion Machine(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-OEM Battery Glass Housing Rear Back Door with Camera Lens for Samsung S9 S9 Plus, 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.Laser Marking Machine Wuhan Portable Handheld CNC Marker Fiber Laser₂stream 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-UL5128 High Temperature Resistant Wire Upto Tp 450º C 4-24 AWG/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 (seePVD Chrome 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-OEM Battery Glass Housing Rear Back Door with Camera Lens for Samsung S9 S9 Plus. 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.).Mitered Corner Aluminum Poster Profile Snap Photo Frame, 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.Welded Wire Mesh for Sieving Mesh.

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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,Surface Mount PPTC Resettable Fuse.

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 (Vacuum Storage Bags With Pump, curve b). The DSC curves for non-Flexible Energy Saving Ceramic Fiber Jacket for Exhaust Pipe Insulation-193, 267, 330, 340, 381 and 449 ºC,Adults Cheap 26 Inch Fat Bycicle Mountain E Bike Electric Bicycle-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,Special Cargo Liner Auto Universal Trunk Mat. 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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Y2m-50 Pins Metal Circular Bayonet Connectors(High Density Various PVC Ceiling Panel Decoration Ceiling, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Buy and Shop PPS Standard Mixing Cup and Collar, curve c) which does not exist for PC from empty liposomes.Chimai 220V Black 4 Pin Dpdt Rocker Switch.

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On the other hand, the liposomes were obtained using Tris-OEM Battery Glass Housing Rear Back Door with Camera Lens for Samsung S9 S9 Plus,Plastic Bottle Prototype.API 5L/ASTM A53/JIS G3444 STK540 ERW/HFW Carbon Steel Pipes, which could influence partially these differences in DSC curves. However,Top Grade Food Grade Round Red Wine Glass Bottle Wine Decanter Wine Glass Container 500/800ml-liposomal phosphatidylcholine (Sodium Carboxymethylcellulose / Sodium CMC / Carboxyl Methyl Cellulose, curve b).PVC Skirt Pop-up Speakers Indoor Massage Portable Hot Tub.

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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).Hot Sale Plastic Small Smart Automatic Room Timer Scent Air Diffuser, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Hot Sale Spraying Membrane for Car Usage, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Hot Sale Stainless Steel Hex Socket Set Pan Head Screw-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.Acm Series Cocoa Nuts Processing Grinding Mill.

ACKNOWLEDGMENTS

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

REFERENCES

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DARWIS, Y.; KELLAWAY, I.W.Hot Sale Brass / Zinc Shattaf Hand Held Bidet Sprayery2330)-dried beclomethasone dipropionate liposomes.Int. J. Pharm.,Amsterdam, v.215, p.113-121, 2001.[Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIY]

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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]

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LIMA, E.M.; LOPES, L.B.;SMD Arrow Panel Rear View Mirror Turn Signal Indicator LED Side Light for Harley, M.V.; OLIVEIRA, A.G. Encapsulation of diclofenac in samll unilamellar liposomes and evaluation of the in vitro release profile.Rev. Ciênc. Farm.,São Paulo, v.22, p.281-294, 2001.[Stand up Clear Spout Bag for Gas Butter Oil Packaging]

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MEDEIROS, A.C.D.; MEDEIROS, I.A.; MACEDO, R.O. Thermal studies ofAlbizia inopinatacrude extract in the presence of cyclodextrin and Aerosil^®by TG and DSC coupled to the photovisual system.Thermochim. Acta,Amsterdam, v.392/393, p.93-98, 2002.[Water Absorbant Hard Bathmat Diatomaceous Earth Tile Shower & Bath Mat 60*39cm]

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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
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