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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) srt2:(2000-2009);pers:(Edwards Katarina)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) > (2000-2009) > Edwards Katarina

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1.
  • Bramer, Tobias, et al. (författare)
  • Catanionic drug-surfactant mixtures : Phase behavior and sustained release from gels
  • 2003
  • Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 20:10, s. 1661-1667
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To study mixtures of SDS and the drugs diphenhydramine, tetracaine, and amitriptyline to compile phase diagrams and to investigate the use of interesting phases for sustained release from gels. METHODS: Phase diagrams were composed by studying large numbers of different compositions of negatively charged SDS and positively charged drug compounds visually, rheologically, and by cryotransmission electron microscopy. Drug release from Carbopol 940 and agar gels containing interesting phases, e.g., vesicle and branched micelle phases, was measured in vitro by the USP paddle method. RESULTS: Vesicles and elongated and branched micelles were formed on the SDS-rich side in all three systems examined. The tetracaine system differed from the other two in that it showed a vesicle area in the drug-rich side. Release of diphenhydramine from Carbopol 940 gels was slowed by at least a factor of 10 when in the form of vesicles or branched micelles. The same delay was found for both drug-rich and SDS-rich tetracaine vesicles. CONCLUSIONS: Mixtures of SDS and positively charged drugs form the same interesting phases as traditional catanionic mixtures. This may prove useful in obtaining functional controlled-release systems when using gels as drug carriers.
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2.
  • Bramer, Tobias, et al. (författare)
  • Effects of pH and ionic strength on catanionic drug-surfactant mixtures used for prolonged release from gels.
  • 2007
  • Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 285-291
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to investigate the influence of pH and ionic strength on the phase behavior of two different catanionic drug-surfactant mixtures, and to study drug release from gels facilitated by the catanionic aggregates. Simplified phase diagrams were constructed for diphenhydramine or tetracaine mixed with SDS, varying the pH approximately between 6 and 11, and the NaCI concentration from 0.45 to 1.8%. The phases formed were studied visually, rheologically and with cryo-TEM. Some mixtures containing catanionic vesicles and micelles were selected for drug release studies from gels, varying the pH and NaCI concentration here as well. Both catanionic systems investigated proved relatively resilient to changes in the ionic strength. Changes in pH, on the other hand, caused marked effects to the phase behavior in both systems. The influence of pH was particularly strong in the drug-rich part of the tetracaine/SDS system, where increasing the pH causes precipitation. As expected, the drug release in both systems was somewhat affected by changes in both pH and ionic strength, but remained in all cases significantly prolonged as compared to the release of free, non-complexed, drug. These studies show that catanionic mixtures may be used to obtain prolonged drug release from gels, and that the concept also works when the gels are exposed to a pH that is a couple of units above the pKa of the cationic component. Furthermore, the ionic strength has no pronounced effect on the drug release, as long as it is kept within reasonable pharmaceutical levels.
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3.
  • Dew, Noel, et al. (författare)
  • Gel formation in systems composed of drug containing catanionic vesicles and oppositely charged hydrophobically modified polymer.
  • 2009
  • Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 70:2, s. 187-197
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to explore if mixtures of drug containing catanionic vesicles and polymers give rise to gel formation, and if so, if drug release from these gels could be prolonged. Catanionic vesicles formed from the drug substances alprenolol or tetracaine, and the oppositely charged surfactant sodium dodecyl sulphate were mixed with polymers. Three polymers with different properties were employed: one bearing hydrophobic modifications, one positively charged and one positively charged polymer bearing hydrophobic modifications. The structure of the vesicles before and after addition of polymer was investigated by using cryo-TEM. Gel formation was confirmed by using rheological measurements. Drug release was studied using a modified USP paddle method. Gels were observed to form only in the case when catanionic vesicles, most likely with a net negative charge, were mixed with positively charged polymer bearing lipophilic modifications. The release of drug substance from these systems, where the vesicles are not trapped within the gel but constitute a founding part of it, could be significantly prolonged. The drug release rate was found to depend on vesicle concentration to a higher extent than on polymer concentration.
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4.
  • Dos Santos, Nancy, et al. (författare)
  • Influence of poly(ethylene glycol) grafting density and polymer length on liposomes : Relating plasma circulation lifetimes to protein binding
  • 2007
  • Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1768:6, s. 1367-1377
  • Tidskriftsartikel (refereegranskat)abstract
    • The incorporation of poly(ethylene glycol) (PEG)-conjugated lipids in lipid-based carriers substantially prolongs the circulation lifetime of liposomes. However, the mechanism(s) by which PEG-lipids achieve this have not been fully elucidated. It is believed that PEG-lipids mediate steric stabilization, ultimately reducing surface-surface interactions including the aggregation of liposomes and/or adsorption of plasma proteins. The purpose of the studies described here was to compare the effects of PEG-lipid incorporation in liposomes on protein binding, liposome-liposome aggregation and pharmacokinetics in mice. Cholesterol-free liposomes were chosen because of their increasing importance as liposomal delivery systems and their marked sensitivity to protein binding and aggregation. Specifically, liposomes containing various molecular weight PEG-lipids at a variety of molar proportions were analyzed for in vivo clearance, aggregation state (size exclusion chromatography, quasi-elastic light scattering, cryo-transmission and freeze fracture electron microscopy) as well as in vitro and in vivo protein binding. The results indicated that as little as 0.5 mol% of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE) modified with PEG having a mean molecular weight of 2000 (DSPE-PEG(2000)) substantially increased plasma circulation longevity of liposomes prepared of 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). Optimal plasma circulation lifetimes could be achieved with 2 mol% DSPE-PEG(2000). At this proportion of DSPE-PEG(2000), the aggregation of DSPC-based liposomes was completely precluded. However, the total protein adsorption and the protein profile was not influenced by the level of DSPE-PEG(2000) in the membrane. These studies suggest that PEG-lipids reduce the in vivo clearance of cholesterol-free liposomal formulations primarily by inhibition of surface interactions, particularly liposome-liposome aggregation.
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5.
  • Gabel, Detlef, et al. (författare)
  • The Anionic Boron Cluster (B(12)H(11)SH)(2-) as a Means To Trigger Release of Liposome Contents.
  • 2007
  • Ingår i: ChemMedChed. - : Wiley. - 1860-7179. ; 2:1, s. 51-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Triggered release. Liposomes are novel carriers for pharmaceutical agents and can be triggered to release their contents by the addition of B12H11SH, a compound in clinical use. As systemic toxicity is decreased relative to the free drug, liposomal drugs can therefore be administered in higher concentrations before dose-limiting side effects are met. Thus, liposome-encapsulated drugs may be of great value in the therapy of diseases.
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6.
  • Johansson, Emma, et al. (författare)
  • On the formation of discoidal versus threadlike micelles in surfactant/lipid systems
  • 2008
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 24:5, s. 1731-1739
  • Tidskriftsartikel (refereegranskat)abstract
    • In a recent study, we showed that the surfactant 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) induced mixed micelles of either threadlike or discoidal shape when mixed with different types of lipids. In this study, we have exchanged the PEG-lipid for the more conventional surfactants octaethylene glycol monododecyl ether (C12E8), hexadecyltrimethylammonium bromide (CTAB), and sodium dodecyl sulfate (SDS). Cryo-TEM investigations show that also these surfactants are able to induce the formation of long-lived discoidal micelles. Generally, the preference for either discoidal or threadlike micelles can be tuned by the choice of lipids and environmental conditions in much the same way as observed for the lipid/PEG-lipid system. Our investigation showed, furthermore, that the choice of surfactant may influence the type of mixed micelles formed. It is argued that the formation of discoidal rather than threadlike micelles may be rationalized as an effect of increasing bending rigidity. Our detailed theoretical model calculations show that the bending rigidity becomes significantly raised for aggregates formed by an ionic rather than a nonionic surfactant.
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7.
  • Köping-Höggard, M, et al. (författare)
  • Chitosan as a nonviral gene delivery system. Structure-property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo
  • 2001
  • Ingår i: Gene Therapy. - 0969-7128 .- 1476-5462. ; 8:14, s. 1108-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Chitosan is a natural cationic linear polymer that has recently emerged as an alternative nonviral gene delivery system. We have established the relationships between the structure and the properties of chitosan-pDNA polyplexes in vitro. Further, we have compared polyplexes of ultrapure chitosan (UPC) of preferred molecular structure with those of optimised polyethylenimine (PEI) polyplexes in vitro and after intratracheal administration to mice in vivo. Chitosans in which over two out of three monomer units carried a primary amino group formed stable colloidal polyplexes with pDNA. Optimized UPC and PEI polyplexes protected the pDNA from serum degradation to approximately the same degree, and they gave a comparable maximal transgene expression in 293 cells. In contrast to PEI, UPC was non toxic at escalating doses. After intratracheal administration, both polyplexes distributed to the mid-airways, where transgene expression was observed in virtually every epithelial cell, using a sensitive pLacZ reporter containing a translational enhancer element. However, the kinetics of gene expression differed - PEI polyplexes induced a more rapid onset of gene expression than UPC. This was attributed to a more rapid endosomal escape of the PEI polyplexes. Although this resulted in a more efficient gene expression with PEI polyplexes, UPC had an efficiency comparable to that of commonly used cationic lipids. In conclusion, this study provides insights into the use of chitosan as a gene delivery system. It emphasises that chitosan is a nontoxic alternative to other cationic polymers and it forms a platform for further studies of chitosan-based gene delivery systems.
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8.
  • Ramsay, Euan, et al. (författare)
  • Transition Metal-Mediated Liposomal Encapsulation of Irinotecan (CPT-11) Stabilizes the Drug in the Therapeutically Active Lactone Conformation
  • 2006
  • Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 23:12, s. 2799-2808
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. To determine whether entrapped transition metals could mediate the active encapsulation of the anticancer drug irinotecan into preformed liposomes. Further, to establish that metal complexation could stabilize liposomal irinotecan in the therapeutically active lactone conformation. Materials and Methods. Irinotecan was added to preformed 1,2-distearoyl-sn-glycero-phosphocholine/cholesterol (DSPC/chol) liposomes prepared in CuSO4, ZnSO4, MnSO4, or CoSO4 solutions, and drug encapsulation was determined over time. The roles of the transmembrane pH gradient and internal pH were evaluated. TLC and HPLC were used to monitor drug stability and liposome morphology was assessed by cryo-TEM. Results. Irinotecan was rapidly and efficiently loaded into preformed liposomes prepared in unbuffered (similar to pH 3.5) 300 mM CuSO4 or ZnSO4. For Cu-containing liposomes, results suggested that irinotecan loading occurred when the interior pH and the exterior pH were matched; however, addition of nigericin to collapse any residual transmembrane pH gradient inhibited irinotecan loading. Greater than 90% of the encapsulated drug was in its active lactone form and cryo-TEM analysis indicated dark intravesicular electron-dense spots. Conclusion. Irinotecan is stably entrapped in the active lactone conformation within preformed copper-containing liposomes as a result of metal-drug complexation.
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9.
  • Strömstedt, Adam A., et al. (författare)
  • Effect of lipid headgroup composition on the interaction between melittin and lipid bilayers
  • 2007
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 311:1, s. 59-69
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of the lipid polar headgroup on melittin-phospholipid interaction was investigated by cryo-TEM, fluorescence spectroscopy, ellipsometry, CD, electrophoresis and photon correlation spectroscopy. In particular, focus was placed on the effect of the lipid polar headgroup on peptide adsorption to, and penetration into, the lipid bilayer, as well as on resulting colloidal stability effects for large unilamellar liposomes. The effect of phospholipid headgroup properties on melittin-bilayer interaction was addressed by comparing liposomes contg. phosphatidylcholine, -acid, and -inositol at varying ionic strength. Increasing the bilayer neg. charge leads to an increased liposome tolerance toward melittin which is due to an electrostatic arrest of melittin at the membrane interface. Balancing the electrostatic attraction between the melittin pos. charges and the phospholipid neg. charges through a hydration repulsion, caused by inositol, reduced this surface arrest and increased liposome susceptibility to the disruptive actions of melittin. Furthermore, melittin was demonstrated to induce liposome structural destabilization on a colloidal scale which coincided with leakage induction for both anionic and zwitterionic systems. The latter findings thus clearly show that coalescence, aggregation, and fragmentation contribute to melittin-induced liposome leakage, and that detailed mol. analyses of melittin pore formation are incomplete without considering also these colloidal aspects.
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