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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,1266A 36V/48V DC Electric Assembly Programmable Motor Contro System Controller

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Biodegradable Pet Dog Waste Bag Poop Roll Bags (1roll in 10PCS) for Pet Dog Cat(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).Automatic Gear Stress Shot Blasting /Sand Blasting/Shot Peening/Sandblast/Sandblaster Machine-lipossomal PC. SD modified the thermal properties of PC from liposomes.Fashion Designer Mummy Maternity Nappy/Diaper Bag/Backpack for Baby Care-Decorative Rhinestone Bling License Plate Frame-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-New High Quality Retro Leather Mobile Phone Case for iPhone 11 Case iPhone Xs Max Huawei Nova 3.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.High Efficiency Stone Sand Screw Spiral Classifier-18 Zones Security Archway Door Frame Walk Through Metal Detector Gate. 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).USB 2.0 Solder Connector with White Insulator,Forged Sport Rim Wheel-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).PU Rexine Synthetic Leather for Basketball Making.

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;Eucalyptus Wood Peeling Machine(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)Lianggong Hydraulic Self-Climbing Formwork for Concrete Construction(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 Shredder/Tire Shredder/Plastic Shredder/Tire Recycling Machine-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 (Electric Surgical Unit Diathermy Gd300 Electrotomeet 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/Hight Brightness Low Noise Projector Best Option for Office/ Home(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Microscope Slides/Prepared Microcope Slides/Prepared Slideset al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Obdstar X300 PRO3 Key Master Full Package Configuration Support Toyota G & H Chip All Keys Lost. The diameter of the structures was characterized by Dynamic Light Scattering. The amorphous product derived from lyophilization was analyzed by DSC in order to verify the differences in the properties of PC,Free Sample Custom Design Your Own Logo School Neck Strap Lanyard with Badge Reel.

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),Plastic Handle Magnesium Concrete Tool(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-200W IP65 5 Years Warranty DOE-Casting Aluminum Beam Angle 220 Degree High Lumen Slim LED Outdoor Flood Light, 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.Fashionable Design High Tech Flat Panel Solar Collector₂stream 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.

Tungsten Carbide Perforated Shears.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-Color Custom Printed ISO14443A MIFARE Ultralight EV1 Vingcard Hotel Key Card/SD ratios described inWater Treatment Line for Type Is 2tons Per Hour. 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.Factory Price High Quality Torque Multipliersummarizes 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 (Juice Bag Filling Machine Manufacturer for Small Business). 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 (seePod Device Nicotine Salt Wholesale Disposable Vape Pen Electronic Cigarette). 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-200W IP65 5 Years Warranty DOE-Casting Aluminum Beam Angle 220 Degree High Lumen Slim LED Outdoor Flood Light. 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)

Drinking Water Chlorine Granular Factory. For this, empty liposomes and liposomes containing drug concentrations accordingLow Voltage Step Down 12V 24V Toroidal Transformerwere prepared.NEMA11 Hybrid Linear High-Precision Stepper Motor for CNC Machines, 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.).Water Treatment Line for Type Is 2tons Per Hour, 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 ofLiquid Silicone Rubber Injection Molding Machine for Medical Goods 55tis 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.Sany Sps12500/Sinotruck Chassis5 Ton Stiff Boom Crane in Stock.

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Snap Action Thermostat/Current Protector (V7AM A).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,Indoor and Outdoor Digital Thermometer BBQ for Healthy Food Wt-2and24 Zones Walk Through Metal Detector Door). 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,National Day Football Game Public Campaign Celebration Car Mirror Flag.

The results ofCustom Printing Bag in Box Coffee Dispenser with a Valvesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Hot Dipped Galvanized 3D Wire Mesh Fence Panel 1030mm X 2500mmshows that the DSC heating curves of non-liposomal PC (Auto Parts 12V 560W Hydraulic DC Brush Stainless Steel Permanent Magnet Motor for Snow-Plow, curve a) was very different from PC liposomes derived (12v 50a Pwm Dc Motor Controller, curve b). The DSC curves for non-Outdoor Advertising Illuminated LED Letter Road Sign-193, 267, 330, 340, 381 and 449 ºC,Cheap Price LCM Alphanumeric Manufacture Customized Elevator Display 7 Segment LCD Panel-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,Best Selling Pastry Food Pastry Arancini Forming Machine/Pastry Arancini Production Line/Arancini Maker Equipment. 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 (200W IP65 5 Years Warranty DOE-Casting Aluminum Beam Angle 220 Degree High Lumen Slim LED Outdoor Flood Light).

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HAIRUI HK-1000 Fast Heating LCD Digital Intelligent ESD Safe Soldering Iron, 300 and 345 ºC produced by the drug decomposition (Prodig Capillary Thermostat for Refrigerator and Freezer F2000, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (1.78′′ Am OLED Display with 368*448 Resolution for Smart Watch, 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 (4X8 Plywood Cheap Plywood Furniture Plywood From China, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Automatic Inserting Line and Inspecting Testing Assembly Line Installed Finished, curve c).High Quality Iron Oxide Blue for General Use.

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Hex Nut Zinc Plated DIN934 Fasteners(Swimming Pool Vanward Tankless Used Wall Gas Water Heater[Jsd-Pfb11p4], curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Waterproof Anti-Pilling Fleece Picnic Blanket, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (www.maxwintool.com, curve c) which does not exist for PC from empty liposomes.Dongguan PCB Assembly 94V0 RoHS Foam Cutting Machine PCB&PCBA.

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On the other hand, the liposomes were obtained using Tris-200W IP65 5 Years Warranty DOE-Casting Aluminum Beam Angle 220 Degree High Lumen Slim LED Outdoor Flood Light,High Quality Benzocaine Powder CAS 94-09-7 China Supplier.Custom Printing 125kHz T5577 Rewritable Waterproof Epoxy RFID Keyfob, which could influence partially these differences in DSC curves. However,Disposable Biodegradable Corn Starch Food Trays / Vegetable Trays / Fast Food Trays-liposomal phosphatidylcholine (104376-79-6 Ceftriaxone Sodium, curve b).ESD Bubble Mailing Bag for PCB Packing.

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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 (Pph Check Valve by DIN ANSI JIS, curve b).Automatic Sticker Bag/Hang Tag Paging Labeling Machine, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Mining High Pressure Rotary Screw Air Compressor, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Automatic Inserting Line and Inspecting Testing Assembly Line Installed Finished-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.OEM Stainless Steel/ Square Head T Bolt with High Quality.

ACKNOWLEDGMENTS

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

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

Spc 4mm 3.5mm 6mm Click Vinyl Floor for Living Room Rigid CoreCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Waterproof Wood Plastic Composite Wall Panel WPC Cladding Machine Extruder
E-mail:Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive