Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Andreas Sachse is active.

Publication


Featured researches published by Andreas Sachse.


International Journal of Pharmaceutics | 2001

Filter extrusion of liposomes using different devices: comparison of liposome size, encapsulation efficiency, and process characteristics

N Berger; Andreas Sachse; J. Bender; Rolf Schubert; Martin Brandl

Liposomes were prepared by stepwise extrusion through 5, 1, 0.4, 0.2, 0.1 and 0.05 microm pore sizes using two different filter-extruders, the continuous high pressure device Dispex Maximator (CE) or alternatively the discontinuous Avestin LiposoFast (DE). The liposome dispersions obtained were compared in terms of particle size, lamellarity and encapsulation efficiency of calcein. The liposomes were smaller with CE than DE at all stages due to higher flow rates and pressure drops, except for final filter pore size (0.05 microm) where both preparations had similar sizes. The particle size analysis technique itself had a strong influence on the liposome sizes measured. For bigger liposomes (extruded through 0.4 microm filters) the Nicomp 370 revealed bigger volume-based mean particle sizes along with more stringent differences between volume-based and number-based diameters than the Malvern Zetasizer. In contrast, for small liposomes extruded through 0.05 microm filters, similar liposome sizes were found no matter which of the two PCS techniques or cryo-transmission electron microscopy was used. In congruence to the liposome sizes measured, encapsulation efficiencies were smaller for CE than DE at all filter stages except the final (0.05 microm). No lipid loss occurred and lyso-phosphatidylcholine formation was negligible irrespective of which extrusion technique was used.


Investigative Radiology | 1997

Biodistribution and computed tomography blood-pool imaging properties of polyethylene glycol-coated iopromide-carrying liposomes.

Andreas Sachse; Leike Ju; Schneider T; Wagner Se; Rössling Gl; Werner Krause; Brandl M

RATIONALE AND OBJECTIVES Surface-modified contrast-carrying liposomes potentially are useful as computed tomography (CT) blood-pool agents. The biodistribution and CT-imaging behavior of conventional as well as polyethylene glycol (PEG)-coated iopromide-carrying liposomes were tested. Two different types of PEG-ylated lipids were used to demonstrate possible differences. METHODS Iopromide-containing liposomes were prepared by a continuous high-pressure extrusion method and subsequently PEG-ylated by simple mixing with either DSPE-PEG2000 or CHHS-PEG2000. The resulting liposomes were investigated in rats (biodistribution) and rabbits (imaging). RESULTS Surface modification with CHHS-PEG consistently resulted in less effective stabilization of liposomes in the blood than with DSPE-PEG. In the biodistribution study, no significant differences in blood concentration could be found 1 hour after injection between the different formulations at a dose of 250 mg total iodine/kg body weight (approximately 500 mg lipid/kg). At this dose, the unmodified as well as the DSPE-PEG liposomes displayed prolonged blood circulation with CT density differences above 70 Hounsfield units (aorta) for up to 20 minutes (n = 1). CONCLUSIONS DSPE-PEG-coated and unmodified liposomes proved to be useful for CT blood-pool imaging displaying favorable imaging properties. Future studies will have to demonstrate whether PEG-ylation offers diagnostic or toxicologic advantages over conventional vesicles in this indication.


International Journal of Pharmaceutics | 1995

Generation of contrast-carrying liposomes of defined size with a new continuous high pressure extrusion method

T. Schneider; Andreas Sachse; G. Röβling; Martin Brandl

A novel continuous high pressure extrusion method was evaluated for the generation of radiopaque and paramagnetic liposomes. The magnetic resonance contrast agent gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) as well as the X-ray contrast agent iopromide were used as water-soluble model substances for liposomal encapsulation. The continuous process, which is introduced here, allows the fast and efficient extrusion of large batches of liposomal preparations with maximum flow rates of 500 ml/min. Applying high pressures up to 10.5 MPa, MLV prepared by the film method were sequentially extruded through polycarbonate membranes of decreasing pore size. Encapsulation efficiency was found to be dependent on lipid composition and concentration, amount of contrast agent in the preparation as well as choice of final pore size for extrusion. Application of freeze-thaw cycles markedly improved the entrapment of iopromide, whereas for Gd-DTPA freeze-thaw surprisingly turned out to have only minor effects. Entrapment values rose with increasing lipid concentration and fell sharply with increasing solute concentration. Mean liposome diameters could be varied using polycarbonate membranes of differing pore sizes. Smaller final pore sizes led to vesicle populations with smaller mean diameters and lower encapsulation efficiencies. Excellent maximum encapsulation efficiencies of more than 50% for iopromide and over 60% for Gd-DTPA were obtained for vesicles with mean diameters of around 100 nm, as determined by photon correlation spectroscopy (PCS) and confirmed by negative-staining electron microscopy. Employing medium contrast (100 mg/g iodine and 180μmol/g Gd) and lipid concentrations (150 mg/g), entrapment values as high as 40% for the X-ray and 50% for the paramagnetic contrast agent could still be achieved. Best results were obtained using a lipid mixture of soy phosphatidylcholine (SPC), cholesterol (Chol) and soy phosphatidylglycerol (SPG) in a molar ratio of 6:3:1 for iopromide and SPC, Chol 7:3 for Gd-DTPA. Liposomal preparations remained stable upon storage at 2–8°C for 6 months. The new continuous high pressure extrusion method proved to be suitable for the generation of large volumes of stable, contrast-carrying liposomes with outstanding encapsulation efficiencies.


Investigative Radiology | 1993

Preparation and evaluation of lyophilized iopromide-carrying liposomes for liver tumor detection.

Andreas Sachse; Leike Ju; Rössling Gl; Wagner Se; Werner Krause

&NA; Sachse A, Leike J, Rö&bgr;ling G, Wagner S, Krause W. Preparation and evaluation of lyophilized iopromide‐carrying liposomes for liver tumor detection. Invest Radiol 1993;28:838‐844. rationale and objectives. The objective of the present investigation was to demonstrate a new method for the production of iopromide‐carrying liposomes. We studied biodistribution and elimination behavior, as well as the computed tomography (CT) liver imaging properties. methods. Iopromide‐containing liposomes were prepared by the ethanol evaporation method and subsequently lyophilized. The resuspended liposomes were tested in rats and rabbits. results. After resuspension, liposomes with a mean diameter of 467 ± 66 nm and an encapsulation rate of 41.5 ± 5.5% were obtained. In rats, a marked accumulation of liposomal iopromide was found in the liver and spleen. In rabbits, complete renal elimination of iopromide within 7 days was demonstrated. At a dose of 150 mg total iodine/kg, a small tumor (<0.5 cm) could be detected in a VX‐2‐bearing rabbit. conclusions. The ethanol evaporation method proved to be suitable for the reproducible large‐scale manufacture of iopromide liposomes with high encapsulation. The resuspended liposomes displayed favorable biodistribution, elimination and imaging characteristics.


Investigative Radiology | 1993

CHARACTERIZATION OF IOPROMIDE LIPOSOMES

Werner Krause; Jens Leike; Andreas Sachse; Gabriele Schuhmann-Giampieri

RATIONALE AND OBJECTIVES.Iopromide-carrying liposomes were prepared and were characterized pharmaceutically and biologically. METHODS.The liposomes were prepared by the ethanol evaporation method and were characterized by quasi-elastic light scattering (size) and equilibrium dialysis (encapsulation efficiency and stability). Acute and subchronic toxicity was tested in mice and/or rats and cardiovascular tolerance in rabbits. Pharmacokinetic parameters were determined in rats. Computed tomography (CT) imaging efficiency was obtained from rat and rabbit studies. RESULTS.The mean diameter was 0.5 ± 0.1 μm and the encapsulation efficiency ranged between 30% and 40%. The liposomes were stable in human and rabbit plasma for approximately 24 hours. The LD50 in mouse and rat was approximately 3 g iodine/kg. In a subchronic toxicity study in rats with six doses of 1 g iodine/kg given every three days, no adverse effects were observed. The pharmacokinetics in rats were dose-dependent. Increasing the dose resulted in lower total clearance, and longer terminal half-life. Elimination of iodine was complete and the main route of excretion was via the kidneys. A clinically relevant computed tomography enhancement of the liver was reached after approximately 200 mg iodine/kg in rats and 150 mg iodine/kg in rabbits. CONCLUSIONS.The iopromide-carrying liposomes were well tolerated in animal studies and seemed to be suitable for the imaging of the liver.


Drug Development and Industrial Pharmacy | 1994

Large-scale production of liposomes of defined size by a new continuous high pressure extrusion device

T. Schneider; Andreas Sachse; G. Röbling; Martin Brandl

A new continuous high pressure extrusion apparatus for the generation of liposomes was designed and tested in the present study. The extruder, which basically consists of an open supply vessel and a high pressure filter holder mounted on a gas-driven pump exhibited superior abilities compared to currently available, discontinuous extrusion devices. Due to continuous flows up to 500 ml/min (filter diameter 47 mm), large batches on a liter scale could be extruded in one step. The maximum pressure of 10.5 MPa employed here, enabled the rapid passage of liposomal preparations with various lipid compositions at lipid concentrations as high as 400 mg/g through polycarbonate membranes without any clogging of the system. Employing final pore sizes between 5.0 and 0.03 μm, the mean vesicle diameter of liposomal preparations could be varied from 400 to 60 nm. Surprisingly high encapsulation efficiencies of two water-soluble contrast agents, iopromide and Gd-DTPA, which we used as model substances, were obtained for...


Academic Radiology | 1999

CT blood pool enhancement in primates with lopromide-carrying liposomes containing soy phosphatidyl glycerol*

Udo P. Schmiedl; Werner Krause; Jens Leike; Andreas Sachse

RATIONALE AND OBJECTIVES The purpose of this study was to determine the feasibility of using iodinated liposomes as blood pool agents for computed tomography (CT) in nonhuman primates. MATERIALS AND METHODS Five normal adult baboons (15-21 kg) were anesthetized and intravenously injected with iopromide containing soy phosphatidyl glycerol liposomes with a diameter of 195 nm. Each animal received a dose of 300 mg total iodine per kilogram (46% encapsulation). RESULTS The animals tolerated the injections well, experiencing no measurable electrocardiographic changes, and recovered uneventfully from anesthesia. Sequential helical CT scans of the baboons from the base of the skull to the symphysis pubis acquired up to 40 minutes after injection showed persistent blood pool enhancement. Maximum mean enhancement of major vascular structures was 106 HU at 1 minute after contrast medium injection. Mean blood pool enhancement was 76, 72, and 67 HU at 10, 20, and 40 minutes after injection, respectively. Liver and spleen were enhanced by 40 and 41 HU, respectively, 40 minutes after injection. No significant enhancement was measured in the brain and pancreas. CONCLUSION Soy phosphatidyl glycerol with iopromide liposomes produces prolonged vascular enhancement and has potential as a blood pool CT contrast agent in primates.


Investigative Radiology | 2001

Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging.

Jens U. Leike; Andreas Sachse; Karsten Rupp

Leike JU, Sachse A, Rupp K. Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging. Invest Radiol 2001;36:303–308. rationale and objectives. Contrast-carrying liposomes are potentially useful as computed tomography (CT) blood-pool agents. In the present study, preliminary safety, pharmacokinetics, and the CT imaging behavior of continuously extruded iopromide-carrying liposomes were studied. methods. Iopromide liposomes were prepared by continuous high-pressure extrusion. Cell membrane–damaging characteristics were assessed in vitro in dog erythrocytes. Acute and subchronic toxicity and pharmacokinetics parameters were determined in rats. Computed tomography imaging efficiency was studied in rabbits. results. The iopromide-carrying liposomes caused only minor morphological changes in dog erythrocytes. The median lethal dose in rats was approximately 4.5 g of total iodine per kilogram of body weight. In a subchronic tolerance study in rats that were administered six doses of 1 g iodine per kilogram twice a week, no adverse effects were observed. The pharmacokinetics in rats was dose dependent, and elimination of iopromide was almost complete within 7 days after intravenous administration. In rabbits, at a dose of 300 mg total iodine per kilogram, the iopromide-carrying liposomes displayed prolonged blood circulation, with mean CT density differences >60 Hounsfield units (aorta) for up to 10 minutes. conclusions. The iopromide liposomes were well tolerated, almost completely excreted, and have potential as a CT blood-pool imaging agent.


Journal of Liposome Research | 1994

Characterization of Iopromide-Carrying Liposomes

Gabriele Schuhmann-Giampieri; Jens Leike; Andreas Sachse; Werner Krause

AbstractIopromide-carrying liposomes were prepared by the ethanol evaporation method and pharmacokinetic parameters and CT imaging efficiency were determined in rats and rabbits. The mean diameter of the liposomes was 0.5±0.1 urn and the encapsulation efficiency was between 30 and 40%. The liposomes were stable in human, bovine, dog, pig, rat and rabbit plasma for more than 6 h. The pharmacokinetics in rats and rabbits were dose-dependent. Increasing the dose resulted in lower total clearance, and longer terminal half-life. Elimination of iodine was complete and the main route of excretion was via the kidneys. A clinically relevant CT enhancement of the liver was reached after 200 mg iodine/kg in rat and 150 mg iodine/kg in rabbit.


International Journal of Pharmaceutics | 1996

Lyophilization and rehydration of iopromide-carrying liposomes

C. Zingel; Andreas Sachse; G. Röβling; Rainer H. Müller

Abstract Iopromide-carrying liposomes prepared by the ethanol-evaporation method which encapsulated approximately 35% X-ray contrast agent at an average vesicle size of 300 nm were stabilized by lyophilization. Freezing behaviour of the suspension was studied by differential scanning calorimetry (DSC) and resistance/temperature measurement with respect to the maximum allowable temperature during primary drying. While melting of the suspension was observed at −21°C by DSC, conductivity changes down to −40°C could be detected by simultaneous resistance/temperature measurement. Furthermore, the influence of two different shelf-temperatures (−15°C and + 5°C) and three different chamber pressures (0.03 mbar, 0.08 mbar and 0.2 mbar) during primary drying on the quality of the lyophilized and rehydrated liposomes were investigated. A chamber pressure of 0.08 mbar and a shelf-temperature of −15°C during primary drying led to optimal product quality indicated by high contrast agent encapsulation. A chamber pressure of 0.08 mbar also proved to be optimal with respect to an economic lyophilization process. The residual water content of the freeze dried material proved to be very low (about 0.1%) independent of process parameters. Rehydration of the lyophilized liposomes with mannitol solution resulted in higher encapsulation efficiency of the rehydrated vesicles compared to rehydration with water or 20 mM tromethamine buffer (pH 7.5). The encapsulation efficiency could be further improved by increasing the concentration of the mannitol solution. Rehydration with iso-osmotic solutions of sucrose and KCl proved not to be as effective as mannitol solution in increasing the encapsulation efficiency of the rehydrated vesicles. Freeze-fracture images of lyophilized drug-free liposomes in contrast to iopromide-carrying liposomes revealed the lyoprotective effect of iopromide.

Collaboration


Dive into the Andreas Sachse's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge