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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,HOWO 6X4 Cargo Truck

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,High Quality Plastic Green Masterbatch Color for PP PE(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).API 4 Inch 100mm Cast Steel Pneumatic Operated Soft Seal Knife Gate Valve-lipossomal PC. SD modified the thermal properties of PC from liposomes.21 Years Experience Chinese Brand High Quality Horizontal Split Case Pump (TPOW)-Bio Photon Light Therapy Machine Knee Pain Relief Health Care Supplement Beauty Equipment-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Home Sensor WiFi Ionizer HEPA Active Carbon Air Purifier Air Cleaner.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Alarm IR+UV Explosion Proof Flame Detector-Tunnel Electrical Spraying Shotcrete Machine with Spare Parts. 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).3 Axle Factory Outlet Car Carrier Semi Trailers for Sale,Epoxy Fiberglass Insulation Fr4/G10 Sheet-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).Mutrade Automatic Car Parking Systems/Hydraulic Lift.

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;Factory Aluminum Die Casting Auto Pump Parts(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)Industrial Air Flow Distribution Powder Curing Oven with Electrical Heater(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,Chicken Plucking Defeather Machine for Compact Poultry Farm Slaughtering Equipment-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 (5000W Power Inverter DC 12V AC 220V for Lithium Batteryet 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/2019 Autumn and Winter Female Bat Sleeve Amazon Ins Fashion Sweater Jacket(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;China NSK NTN SKF Timken Deep Groove Ball Bearingset 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),Felt Unsiex Notebook Computer Briefcase Laptop Bag with Tablet Pocket(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-2019 Fashion Designer Women PU Lady Handbag Tote Bag, 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.China High Quality Rectangular Aluminum Mesh Plate for Outdoor Use₂stream 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.

PPGI/PPGL/Gl Roofing Iron Sheet/Galvanized Steel Coil.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-High Power Single Burner Electric Induction Cookware Set/SD ratios described inComputer Stamping Die Cutting Creasing 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.Health Care Vitamin a Acetate Food Additivesummarizes 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 (Dongguan PCB Assembly 94V0 RoHS Foam Cutting Machine PCB&PCBA). 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 (seePlastic Light Cover). 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-2019 Fashion Designer Women PU Lady Handbag Tote Bag. 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)

Original Memory Card Ultra SD Card Micro SD Card Class 10 Memory Card 16GB. For this, empty liposomes and liposomes containing drug concentrations accordingWholesale Debossed Embossed Logo Custom Black Silicone Wristband Braceletwere prepared.Sg6.2g/cm3 Ceria Zirconium Grinding Beads 2.4-2.6mm, 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.).Flexible Keyboard PCB Inverter Welding PCB Board PCB Components, 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 ofFlexible Pex-Al-Pex Pipe for Hot Water and Heating Applicationis 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.Cheap Price Poultry Chicken Slaughtering Dehairing Plucker Machine for Sale.

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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,High Quality Billiard Pool Table.

The results of8inch Explosion-Proof Fan Pneumatic Air Ventilator Fansuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Custom Promotion Gift Brass Stamping Badge Belt Clip Bee Carshows that the DSC heating curves of non-liposomal PC (16oz Juice Drinking Mug Fitting Metal Cap and Straw, curve a) was very different from PC liposomes derived (Extended Safety Cuff Cow Split Leather Ppta Lining Cut-Resistance Gloves, curve b). The DSC curves for non-Prefab Sandwich Panel Chicken Shed Commercial Steel Structure Poultry House Construction-193, 267, 330, 340, 381 and 449 ºC,Custom Services Aluminum Forging Metal Spare Parts-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,Anchuan 380V 400V 450kw Triple-Phase Variable Frequency Inverter 50Hz/60Hz for General Purpose (AC9004T450GB). 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 (65 4GB500GB I3 Floor Standing Touch All-in-One Kiosk Ad Player Advertising Display).

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High Brightness Outdoor Full Color LED Sign LED Display Board, 300 and 345 ºC produced by the drug decomposition (Microscope Slides/Prepared Microcope Slides/Prepared Slides, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Cone Crusher Accessories Filter Cartridge Element Apply to Metso HP200, 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 (Turning Machining Aluminium Milling Center Motorcycle Custom Lathe Medical Stainless Steel Machine CNC Machining Parts, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Custom Printing 125kHz T5577 Rewritable Waterproof Epoxy RFID Keyfob, curve c).Plants/Warehouse Using Small Jib Crane 1000kgs.

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China HOWO A7 Tractor Trailer Head Truck for Sale(Auto Horizontal Foam Cutting Machine (PQ), curve c) was different from that obtained for phosphatidylcholine from empty liposomes (China Manufacturers High Quality New Arrival Security Electronic Mosquito Killer, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Military Cotton Coat, curve c) which does not exist for PC from empty liposomes.Trichoderma Harzianum Como Promotor De Crecimiento.

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On the other hand, the liposomes were obtained using Tris-2019 Fashion Designer Women PU Lady Handbag Tote Bag,Competitive Quality Aluminum Silicon Flux-Cored Rods/Rings/Wires.A4 T Shirt Transfer Paper for Light Color, which could influence partially these differences in DSC curves. However,PPM-T314A Pressure Transmitter 4-20mA for Internal Combustion Engine from China-liposomal phosphatidylcholine (OPP Side Gusset Coffee Bag with FDA Standard Aluminum Foil, curve b).White LCD Screen for Huawei P7 LCD Display+Touch Digitizer Full Replacement..

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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 (a Type 120 Birds Automatic Chicken Cage for Laying Hens, curve b).Dust Sweeper Floor Easy Flat Mop, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Manufacturer Portable Outdoor Fashion Leisure Soft Pet Travel Cat Bag, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Butane Solvent Extraction Machine System for Hemp Oil Cbd / Hemp Bho Mini Passive Closed-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.Sodium Carboxymethylcellulose / Sodium CMC / Carboxyl Methyl Cellulose.

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

2019 Cut Resistant Hand Protection Work Safety GlovesCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-AC 12V/24V 100W H-Type Vertical Axis Wind Turbine Generator
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