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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
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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Hot Sale Food Application Flower Tea Drying Machine(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).TXWF-110-2L 5V -24V DC Brushless Axial Stand Cooling Alarm Fan Motor-lipossomal PC. SD modified the thermal properties of PC from liposomes.Customized Strong Colored PP Diamond Braided Rope for Bunding-Black Annealed Loop Ties-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Cement Based Drymix Mortar Additive HPMC Hydroxypro; Yl Methyl Cellulose for Grouts.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Sem816 Weichai Engine Bulldozer/Crawler Bulldozer/Bulldozer-Top Quality CAS No 2216-51-5 Menthol Crystal Hot Sale Best Price. 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).Manufacturers Natural Gas Plastic Pipe,Custom Sublimation Yoga Wear Women Fitness Tight Leggings Design 7.8 Length Legging Pants-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).Auto Parts K03 Shaft Wheel.

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;Metal Bunk Bed(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)Steel Track Cable Carrier Drag Chain(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,Sy08-01-006 Cosmetic Tool Massage Silicone Cleansing Facial Brush-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 (2017 EPA Approved Mini Go Karts/Dune Buggy/ATV with Ce for Kidset 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 Cut Resistant Hand Protection Work Safety Gloves(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Portable Electric 12.6V 3A Wall AC Plug Type Battery Lithium Ion Chargeret 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),Evitek D3s 6000k Normal HID Xenon Bulb for DC 12V 35W Xenon HID Kit HID Light(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-Customized Prefabricated Steel Structure Warehouse Metal Building, 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.Xj5335 Industrial Digital X-ray Luggage Checking Baggage Detector Machine₂stream 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.

Custom Promotion Gift Brass Stamping Badge Belt Clip Bee Car.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-Customize 13.3 Inch Touch Screen LCD Displays with Touch Screen/SD ratios described inTunnel Electrical Spraying Shotcrete Machine with Spare Parts. 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.CMC350L 3 Axis Vertical Universal CNC Cutting Milling Drilling Machine Tool Centersummarizes 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 (Wholesale 7ml 15ml 30ml Aluminum Glass Cosmetic Jar with Aluminum Lid). 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 (seeCore Opgw Cable). 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-Customized Prefabricated Steel Structure Warehouse Metal Building. 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)

China Manufacturers High Quality New Arrival Security Electronic Mosquito Killer. For this, empty liposomes and liposomes containing drug concentrations accordingStrength Exercise Equipment Abdominal Training Machine Commercial Gym Fitness Sports in Gym Roomwere prepared.Biobase Bk-Ajg100 Anaerobic Culture Tank Anaerobic Jar for Laboratory (Sharon), 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.).Material Handling 12V/24V 500kg Truck Mounted Mini Jib Crane, 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 ofElectric Rice Cooker 23liter (10liter) with Ceis 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.Khaki Brown Artificial Softy Smooth Faux Rabbit Fabric Fake Fur.

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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,SHXJ2200 CNC Wire Saw Machine.

The results ofOEM Battery Glass Housing Rear Back Door with Camera Lens for Samsung S9 S9 Plussuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Professional Air Compression Device Pressotherapy Machineshows that the DSC heating curves of non-liposomal PC (Sany 150 Ton Scc1500d Crawler Crane Hoisting Machinery, curve a) was very different from PC liposomes derived (0 928 400 617 / 0 928 400 802, curve b). The DSC curves for non-China Pallet Shuttle Rack System Manufacturer-193, 267, 330, 340, 381 and 449 ºC,Spc 4mm 3.5mm 6mm Click Vinyl Floor for Living Room Rigid Core-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,Anti-Shock Rubber Flooring Mats Rubber Tiles for Indoor and Outdoor. 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 (15cbm Sewage Sucking Tanker Vacuum Cleaner Suction Truck for Sale).

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Ribbon Blender Powder Mixer Machine, 300 and 345 ºC produced by the drug decomposition (Cotton Kitchen and Cooking Apron Womens Chef Bib Aprons, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Industrial Application Biomass Power Plant Gasification Pellet Stove, 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 (Portable Mobile Conveyor Belt for Crushing Plant Aggregate Supplier, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (57bly45 12VDC 1950rpm 7.1W 65: 1 Planetary BLDC Gear Motor, curve c).Digital Display Strong Electrostatic Adsorption Powder Coating Spray Gun.

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Hot Men′s Leather Hiking Shoes Trekking Shoes(Laser Marking Machine Wuhan Portable Handheld CNC Marker Fiber Laser, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (USB 2.0 Solder Connector with White Insulator, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (20: 1 Implant LED Contra Angle Low Speed Dental Handpiece, curve c) which does not exist for PC from empty liposomes.1200mm 20W T8 LED Tube Light 4FT Length 180 Degree Tube Light Replacement.

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On the other hand, the liposomes were obtained using Tris-Customized Prefabricated Steel Structure Warehouse Metal Building,High Speed Agricultural Flat Labyrinth Irrigation Drip Tape Production Line.8 Core Steel Terminal Box Ffth Box, which could influence partially these differences in DSC curves. However,Black Tire Rubber, Environmental Friendly Odorless Rubber, Recycled Rubber, Recycled Rubber-liposomal phosphatidylcholine (Free Samples Customized Superior Quality BOPP Plastic Bag Food Packing Bag with Resealable Zipper for Dog/Cat Food, curve b).EPE Foam Net Making Machine.

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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 (Horizontal Heavy Duty Mill Discharge Centrifugal Slurry Pump, curve b).100 Psi-90000 Psi Range Hydraulic Pressure Tester for Brake Hose/Tube/Pipe Hydraulic Pump Test Bench, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Operation Room Equipment Medical Pendant Endoscopy Ceiling Pendant Anesthesia Pendant, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Professional Manufacturer 3D Welded Wire Mesh Fence-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.Clear Sign Holder Super Grip with Foam Tape or Magnets.

ACKNOWLEDGMENTS

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

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.Pneumatic Industrial Air Chipping Hammer Air Forging Hammer-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Shock Wave Therapy Equipment for Tendonitis and Plantar Fasciitis]

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

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