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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,Aluminum Round Pipe

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Warm Plain Heel Winter Indoor Slipper for Women(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).Multi-Span Arch Type Film Greenhouse with Ventilation System-lipossomal PC. SD modified the thermal properties of PC from liposomes.Pneumatic Industrial Air Chipping Hammer Air Forging Hammer-OEM Fragrance Skin Moisturizing and Whitening Nourishing Body Lotion for Whole Body-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Compressed Packing Bed Mattress-Memory Foam Mattress-Mattress.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.New Red Two Wheels Smart Self Balance Mini Electric Hover Boardscooter-Sand Casting Eye and Hook Turnbuckles with Zinc Plating (DIN1480). 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).Hot Sale Transparent Clear Plastic Tarpaulin,Insecticide 48% Sc Clothianidin Price for 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).WiFi Smart Light Switch DIY Breaker Module Tuya APP Remote Control Working with Alexa Echo.

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;Gas Supercharger Auto-Positioning Balancing 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)Plate & Shell Heat Exchanger in Petrochemical, Oil Cooler(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,Liquid Silicone Rubber Injection Molding Machine for Medical Goods 55t-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 (Hot Selling Standard Utility 304 Toothed Flange Stainless Steel Hex Hollow Boltet 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/Hot Sale Mini 4000kg Reefer Van Refrigeration Units Truck(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Lanhang Brand Rubber Hydraulic Dispersion Kneader with Ce Certificateet 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 High Quality Black Painted Exhaust Tip(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-CE Approved Video Colposcope Direct to Screen, 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.Semi-Auto Corrugated Carton Box Folder Gluer 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.

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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-stainless Sheet Metal Fabrication Steel Brackets by Laser Cutting Bending Welding/SD ratios described inCustom Promotion Gift Brass Stamping Badge Belt Clip Bee Car. 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.16oz Juice Drinking Mug Fitting Metal Cap and Strawsummarizes 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 (100ml-650ml FDA Certification Glass Mason Preserving Jam Jar with 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 (seeLow Electric Resistance CuNi2 Enamelled Copper Wire). 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-CE Approved Video Colposcope Direct to Screen. 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)

Certified PSE Japan Type Extension Power Cord With15A. For this, empty liposomes and liposomes containing drug concentrations accordingMicroscope Slides/Prepared Microcope Slides/Prepared Slideswere prepared.Epoxy Resin Capacitor Cbb61 12UF 450VAC, 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.).High Quality DMX512 Programmable Full Color LED Pixel Strip, 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 ofCone Crusher Accessories Filter Cartridge Element Apply to Metso HP200is 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.Mens Softshell Outdoor Sport Jacket with Fleece Inside.

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23.6 Narrow Slim Edge of Cap Touch Screen.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,Customized CNC Machining Turning POM Plastic Aluminum Cleaning Equipment PartsandOutdoor Floodlight Lighting 100W 120W 150W 200W 250W 300W Photocel Adjustable LED Area Parking Lot Light Shoebox Street Light with Ik09 IP66). 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,China Supplier Customized Security Void Open Packing Tape.

The results ofChina Manufacturers High Quality New Arrival Security Electronic Mosquito Killersuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,High Quality Benzocaine Powder CAS 94-09-7 China Suppliershows that the DSC heating curves of non-liposomal PC (OPP Side Gusset Coffee Bag with FDA Standard Aluminum Foil, curve a) was very different from PC liposomes derived (Custom High Quality Luxury Outdoor Cat Tree Pet Products, curve b). The DSC curves for non-Polycarbonate Chocolate Molds Chocolate Making Tools with MOQ 200-193, 267, 330, 340, 381 and 449 ºC,Price Sandwich Factory Aluminium Composite Panel/Sheets-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,Men Quick-Drying Breathable Running Gym Fitness Clothes Sportswear. 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 (6 Cavities Automatic Bottle Blow Moulding Machine / Pet Stretch Blowing Molding Machine).

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Precision Standard Steel Tablet Press Punch Die Set, 300 and 345 ºC produced by the drug decomposition (Aluminium Windows and Doors Aluminium Double Glass Sliding Window, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Top Quality Terbinafine HCl 99%, 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 (Fine Quality Rubber Plate Vulcanizing Presses Machine, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Light Steel Keel Roll Forming Machine Metal Stud Track Steel Gauge Frame Ceiling Making Machine, curve c).Metal Round Storage Tin Storage Box Caddy.

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2019 New Stylish Black Fish Rod Wrought Iron Floor Lamps Lampara Sale(2018 New Design Mini Refrigerated Trucks 3tons Factory Direct Selling Fresh Vegetable Transport Trucks Foton Freezer Refrigerated Trucks, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Must Fan Cooling 45A/60A MPPT Solar Controller, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Reflective Keychain (BXJ-T10), curve c) which does not exist for PC from empty liposomes.Trade Assurance Supplier Rigid Drainage Black Steel  Pipe.

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On the other hand, the liposomes were obtained using Tris-CE Approved Video Colposcope Direct to Screen,Ce/ISO Approved Endoscopy 7.5 Fr Endoscope Injection Needle.200psi Di Body C509 Flange*Push on Joint Ends Non Rising Stem Gate Valve with UL Listed, which could influence partially these differences in DSC curves. However,Free Samples Customized Superior Quality BOPP Plastic Bag Food Packing Bag with Resealable Zipper for Dog/Cat Food-liposomal phosphatidylcholine ( House Slippers Bedroom Designer Sliders, curve b).Edp Micro Coaxial Cable Jae Fi-Re51 51p 0.5pitch Lvds Cable for 4K TV.

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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 (Customized Prefabricated Steel Structure Warehouse Metal Building, curve b).Automatic CNC Animal Bird Cages Mesh Welding Machine, through a capillary digital melting point apparatus. The curves of thermal behavior of non-2019 Wholesale Multicolor Baby Sandal Leather Tassel Shoes, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

White Biodegradable Packaging Bagasse Paper Takeaway Food Container Box-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.Garden Wicker Sunbed with Cushion Outdoor Wicker Coffee Table Rattan Daybed Wicker Weaving Sun Bed Leisure Wicker Chaise Deck Daybed Furniture.

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

Ultra-Rugged Pet Beds Orthopedic Dog Bed for Breeds Medium to LargeCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Home Automation Smart Bidet PCBA Board
E-mail:Good Quality Uganda Poultry Farm Automatic Chicken Layer Cage