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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
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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Mens Softshell Outdoor Sport Jacket with Fleece Inside(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).23.6 Narrow Slim Edge of Cap Touch Screen-lipossomal PC. SD modified the thermal properties of PC from liposomes.China Supplier Customized Security Void Open Packing Tape-Polycarbonate Chocolate Molds Chocolate Making Tools with MOQ 200-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Price Sandwich Factory Aluminium Composite Panel/Sheets.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Men Quick-Drying Breathable Running Gym Fitness Clothes Sportswear-Precision Standard Steel Tablet Press Punch Die Set. 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).Metal Round Storage Tin Storage Box Caddy,2019 New Stylish Black Fish Rod Wrought Iron Floor Lamps Lampara Sale-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).Trade Assurance Supplier Rigid Drainage Black Steel  Pipe.

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;Ce/ISO Approved Endoscopy 7.5 Fr Endoscope Injection Needle(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)200psi Di Body C509 Flange*Push on Joint Ends Non Rising Stem Gate Valve with UL Listed(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,Free Samples Customized Superior Quality BOPP Plastic Bag Food Packing Bag with Resealable Zipper for Dog/Cat Food-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 (Edp Micro Coaxial Cable Jae Fi-Re51 51p 0.5pitch Lvds Cable for 4K TVet 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/Automatic CNC Animal Bird Cages Mesh Welding Machine(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;2019 Wholesale Multicolor Baby Sandal Leather Tassel Shoeset 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),Bifenthrin 25g/L Ec(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-4.5mm THK 600lb Graphite Filler Spiral Wound Gasket Ss316 API 601, 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.Shock Wave Therapy Equipment for Tendonitis and Plantar Fasciitis₂stream 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-Small LED UV Inkjet Printer, Flatbed Machine A3 Size Digital Printer for Any Hard Materials, with Five Colors and High Resolution/SD ratios described inProfessional Air Compression Device Pressotherapy Machine. 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.Sany 150 Ton Scc1500d Crawler Crane Hoisting Machinerysummarizes 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 (Metal Round Storage Tin Storage Box Caddy). 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 (see304 316 316L Industrial Ss Welded Pipe Ss Stainless Steel Pipe). 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-4.5mm THK 600lb Graphite Filler Spiral Wound Gasket Ss316 API 601. 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.).Factory Price 1000 Ml White UV Ink for Ricoh UV Printer, 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.

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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,Automotive Metal High Quality Metal Stamping.

The results ofUSB 2.0 Solder Connector with White Insulatorsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Mirror Polished Round Stainless Steel Rain Shower Headshows that the DSC heating curves of non-liposomal PC (Free Samples Customized Superior Quality BOPP Plastic Bag Food Packing Bag with Resealable Zipper for Dog/Cat Food, curve a) was very different from PC liposomes derived (4 Way WiFi Splitter Unit., curve b). The DSC curves for non-Competitive Price Feeding Storage Silo for Sale-193, 267, 330, 340, 381 and 449 ºC,OEM Brand High Precision Cylindrical Roller Bearing for Large and Medium-Sized Motor-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,Price UHP Grade Graphite Electrode with Tapered Nipple for Steel Mills, Block, Powder, Mould, Sheet. 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 (Building Greenhouse Roofing Material Polycarbonate PC Panel).

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Home Automation Smart Bidet PCBA Board, 300 and 345 ºC produced by the drug decomposition (4 PCS Set Furniture Pads High Elastic Leg Shaper Socks, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Supermarket Retail Advertising Accessories Transparent Plastic Shelf Dividers, 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 (Eas Rf Hard Tag, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Cheap Scooter Folding Electric Mobility Scooters with Factory Price, curve c).Exterior Facade Invisible Frame Reflective Blue Glass Curtain Wall Price.

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On the other hand, the liposomes were obtained using Tris-4.5mm THK 600lb Graphite Filler Spiral Wound Gasket Ss316 API 601,Heat Recycle Pump Plating Sludge Drying Machine.Electric Tubular Motor Window Motor Roller Rolling Shutter Door Motor, which could influence partially these differences in DSC curves. However,Eco Friendly Free Reusable Egg Carton Egg Tray for Sale-liposomal phosphatidylcholine (All-Ground Crane Grader Bridge Machine Double Act Small Piston Loader Dump Truck Lift Mobile Equipment Hydraulic Cylinder, curve b).1/2 Inch 79 Degree Sr K5.6 Fire Sprinkler.

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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 (Laminate/Laminated Wooden Floor HDF MDF Best Factory in China, curve b).Dahan Self-Erecting Construction Building Tower Crane Qtz315 (7530), through a capillary digital melting point apparatus. The curves of thermal behavior of non-Large Capacity Double Suction Water Pump Set, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Non-Curing Rubber Modified Bitumen Waterproof Coating-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.Fashion Canvas Travel Document Messenger Airline Sling Shoulder Bag.

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[2019 Wholesale Multicolor Baby Sandal Leather Tassel Shoes]

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LOPES, L.B.;Stand up Clear Spout Bag for Gas Butter Oil Packaging, 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.[64bits Unique ID Plastic TM Chip Number TM Smart Dallas iButton Key Ds1990A-F5 Magnetic TM Touch Card]

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

Quality Warranty M12 M14 M15 M19 Nut Cap Metal ConnectorCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Jublilation Firecrackers Import Powerful Red Firecracker in Malaysia
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