Michael Ausborn

Novartis, Bâle, Basel-City, Switzerland

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Publications (8)37.35 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Encapsulation and electron microscopy studies have shown that aqueous dispersions of several nonionic emulsifiers with sucrosepalmitatestearate (SPS) structure and cholesterol (Chol) result in synthetic lipid vesicles. This was demonstrated for the commercial emulsifier sucrosepalmitatestearate for the first time. Such vesicles were able to entrap aqueous solutes, for instance the fluorescence marker carboxyfluorescein (CF) for a period of more than 10 weeks with latencies of about 90 per cent. Though SPS/Chol-vesicles tended to flocculate--especially in concentrated solutions--the efflux of entrapped solutes after storage was lower in these vesicles compared with liposomes consisting of natural egg phosphatidylcholine (EPC) and cholesterol.
    Journal of Microencapsulation 09/2008; 6(1):95-103. DOI:10.3109/02652048909019906 · 1.88 Impact Factor
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    ABSTRACT: To characterize protein stability in poly(lactide-co-glycolide) 50/50-glucose star (PLGA-Glu) injectable millicylinders and to compare results with linear PLGA 50/50. Bovine serum albumin (BSA), a model protein, was encapsulated in PLGA-Glu and linear PLGA millicylinders by solvent-extrusion and incubated under physiological conditions. Important system properties were characterized, including: polymer molecular weight distribution, soluble acidic residues, polymer morphology, polymer water uptake, microclimate pH, protein content and release, and protein aggregation. The polymer microclimate late in the release incubation was simulated and protein recovery was analyzed by UV280, size exclusion chromatography, amino acid analysis, and a modified Bradford assay. PLGA-Glu contained higher levels of low molecular weight oligomers, more rapidly biodegraded, and exhibited a lower microclimate pH than the linear 50/50 PLGA, which is the most acidic type in the PLGA family. BSA, when encapsulated in PLGA-Glu millicylinders, underwent extensive noncovalent insoluble aggregation over 2 weeks in vitro release, which was almost completely inhibited upon co-encapsulation of Mg(OH)2. However, by 5 weeks release for base-containing formulations, although insoluble aggregation was still suppressed, the soluble fraction of protein in the polymer was unrecoverable by the modified Bradford assay. Polymer microclimate simulations with extensive protein analysis strongly suggested that the low recovery was mostly caused by base-catalyzed hydrolysis of the oligomeric fraction of BSA. In PLGA-Glu, the acidic microclimate was similarly responsible for insoluble aggregation of encapsulated BSA. BSA aggregation was inhibited in millicylinders by co-incorporation into the polymer an insoluble base, but over a shorter release interval than linear PLGA likely because of a more acidic microclimate in the star polymer.
    International Journal of Pharmaceutics 07/2008; 357(1-2):235-43. DOI:10.1016/j.ijpharm.2008.02.004 · 3.79 Impact Factor
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    ABSTRACT: A first feasibility study exploring the utility of poly(ethylene carbonate) (PEC) as coating material for drug eluting stents under in vitro conditions is reported. PEC (Mw 242 kDa, Mw/Mn=1.90) was found to be an amorphous polymer with thermoelastic properties. Tensile testing revealed a stress to strain failure of more than 600%. These properties are thought to be advantageous for expanding coated stents. In vitro cytotoxicity tests showed excellent cytocompatibility of PEC. Based on these findings, a new stenting concept was suggested, pre-coating a bare-metal stent with PPX-N as non-biodegradable basis and applying a secondary PEC coating using an airbrush method. After manual expansion, no delamination or destruction of the coating could be observed using scanning electron microscopy. The surface degradation-controlled release mechanism of PEC may provide the basis for "on demand" drug eluting stent coatings, releasing an incorporated drug predominantly at an inflamed implantation site upon direct contact with superoxide-releasing macrophages. As a release model, metal plates of a defined size and area were coated under the same conditions as the stents with PEC containing radiolabelled paclitaxel. An alkaline KO(2-) solution served as a superoxide source. Within 12 h, 100% of the incorporated paclitaxel was released, while only 20% of the drug was released in non-superoxide releasing control buffer within 3 weeks.
    Journal of Controlled Release 03/2007; 117(3):312-21. DOI:10.1016/j.jconrel.2006.11.003 · 7.26 Impact Factor
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    ABSTRACT: Biodegradation and biocompatibility of poly(ethylene carbonate) (PEC) was examined using an in vivo cage implant system. Exudate analysis showed that PEC and PEC degradation products were biocompatible and induced minimal inflammatory and wound healing responses. Adherent foreign body giant cells (FBGCs) caused pitting on the PEC surface, which led to extensive degradation over time. Data obtained from molecular weight and examination of film cross-sections in the scanning electron microscope (SEM) indicated that PEC underwent surface erosion with no change to the remaining bulk. Attenuated total reflectance infrared (ATR-FTIR) spectroscopy was used to characterize the chemical degradation. Superoxide anion released from inflammatory cells appeared to initiate an "unzipping" mechanism of degradation by deprotonation of PEC hydroxyl end groups. The resulting alkoxide ion participated in a concerted mechanism involving water and the carbonate carbonyl, leading to elimination of ethylene glycol. Carbonate ions decomposed further with release of carbon dioxide to regenerate alkoxide ion.
    Journal of Controlled Release 01/2004; 93(3):259-70. DOI:10.1016/j.jconrel.2003.08.010 · 7.26 Impact Factor
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    ABSTRACT: The goal of this study was to exploit molecular recognition of cell surface receptors by viral surface glycoproteins as a means for the selective intracellular delivery of macromolecules. To accomplish this, artificial viral envelopes (AVE) resembling the human immunodeficiency virus-1 (HIV-1) were designed as a model system. Recombinant HIV-1 surface glycoprotein gp160 (HIV-1 rgp160) was inserted in the artificial envelope by a two-step detergent dialysis process. The artificial HIV-1 envelope recognized the CD4 cell surface receptor. FITC-dextran and ricin A were employed as model macromolecules as they cannot passively diffuse across cell membranes. Selective transfer of FITC-dextran encapsulated in HIV-1 rgp160 AVE into a CD4-positive cell line (REX-1B) versus a CD4-negative cell line (KG-1) was demonstrated. Ricin A at concentrations as low as 2 ng/ml arrested cell growth of CD4-positive MOLT-4 cells, whereas 8 ng/ml ricin A in solution had no effect on cell growth. The arrest of cell growth was reverted in the presence of excess anti-gp120 monoclonal antibody. Naked envelopes (without HIV-1 rgp160 inserted) were also found to interact with cells and transfer material, although less efficiently and in a non-specific manner. Viral mimicry using AVE may be a means for targeted intracellular delivery of peptides, proteins, enzymes, toxins, oligodeoxynucleotides, gene constructs, and other non-diffusive, labile or toxic macromolecules.
    Journal of Molecular Recognition 01/1995; 8(1-2):59-62. DOI:10.1002/jmr.300080110 · 2.34 Impact Factor
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    ABSTRACT: Studies of the protective effects of different amounts of sucrose and glucose and a carbohydrate directly linked to the liposome surface on large unilamellar vesicles (LUV) built from soybean phosphatidylcholine (SPC) during lyophilization were carried out. Analyses of freeze-dried liposomes were conducted by particle size determination, retention of entrapped water-soluble marker and lipid mixing assay employing resonance energy transfer (RET). The extent of functionality of carbohydrates depends on their concentration and results from spacing mainly preventing fusion at low concentrations, membrane stabilization preventing leakage and the bulk sugar matrix mainly depressing aggregation at higher concentrations. By incorporating hexadecyl-β-D-galactopyranoside in SPC-LUV as membrane-bound cryoprotectant it could be shown that fixation of the sugar head of galactosides at the membrane surface only leads to prevention of fusion of liposomes. Although the galactoside does not exhibit a membrane stabilizing effect alone, it improves the protective effects of the free carbohydrates hyperadditively. However, this fact is discussed on the basis of sugar-sugar interactions by means of hydrogen bonding.
    International Journal of Pharmaceutics 07/1994; 107(2-107):99-110. DOI:10.1016/0378-5173(94)90447-2 · 3.79 Impact Factor
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    ABSTRACT: Liposomes were prepared from natural (EPC) and hydrogenated (HEPC) egg phosphatidylcholine, with and without cholesterol (CHOL), from sucrose fatty acid ester (SPS7; sucrose-palmitate/stearate) with CHOL and dicetylphosphate (DCP) or from EPC and HEPC with the mono-, di- and tri-ester of SPS7. The cryoprotective activity of sucrose or membrane-bound sucrose fatty esters was assessed. Vesicles were frozen and thawed, or freeze-dried and reconstituted, and retention of the encapsulated marker 5,6-carboxyfluorescein (CF) was monitored. CF retentio n decreased with decreasing freezing temperature, while increasing concentrations of sucrose provided increasing cryoprotection during freezing and thawing. SPS7 vesicles were fully protected by 0.6 M sucrose, whereas equimolar mixtures of EPC and HEPC with SPS7 required 1 M sucrose for complete protection. EPC/CHOL liposomes retained maximally 85% and HEPC/CHOL liposomes 95% marker at the highest sucrose concentration. Lyophilized liposomes without sucrose or in mixture with the SPS mono- or diester retained <10% CF. Lyophilization of EPC and HEPC liposomes in the presence of 0.4 M sucrose resulted in 75% retention of originally encapsulated marker. Differential scanning calorimetry showed a significant reduction of the transition temperature (Tc) of lyophilized HEPC liposomes in the presence of sucrose and the SPS monoester. Infrared spectroscopy indicated sucrose and the SPS monoester forming strong hydrogen bonds with phosphate head groups which supports the water replacement of ‘pseudohydration’ hypothesis.
    Journal of Controlled Release 05/1994; 30(2-30):105-116. DOI:10.1016/0168-3659(94)90257-7 · 7.26 Impact Factor
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    ABSTRACT: Although liposome-encapsulated antibiotics designed for intrapulmonary delivery by instillation or aerosolization have been proposed, little is known about the pharmacokinetic profile and toxicity of liposomal drug formulations when delivered to the lung. A technique for large-scale preparation of sterile amikacin liposomes including preparation of a lyophilized amikacin/phospholipid coprecipitate and a highly efficient hollow-fiber dialysis method for rapid removal of unencapsulated drug is described. Doses of 5 and 15 mg/kg amikacin solution or 15 and 45 mg/kg amikacin-containing liposomes consisting of soy phosphatidylcholine/ phosphatidylglycerol (SPC/PG 7:3, molar ratio) or SPC/PG with cholesterol (SPC/PG/CH 4:3:3) were administered intratracheally into intubated, awake sheep. For the 15 mg/kg amikacin solution, the terminal half-life time () was 117 min with maximum plasma levels (cpmax) of 8.3 μg/ml after 2 h and a bioavailability of 38%. The for both doses of amikacin-SPC/PG liposomes was greater than 3 h. Bioavailability varied from 35 to 58%, with a cpmax of 5.5 μg/ml (15 mg/kg) and 23.6 μg/ml (45 mg/kg) after 1.5 h. The of amikacin-SPC/PG/CH liposomes was greater than 10 h with a cpmax of 3.3 μg/ml after 3 h and a bioavailability of 46%. The dosage form was found to be the overall rate-limiting factor for amikacin pharmacokinetics. For assessment of pulmonary function and blood gases, awake sheep inhaled plain liposomes consisting of 15 and 150 mg/ml SPC or hydrogenated SPC (HSPC) for 30 min via a Collision nebulizer. Dynamic compliance (Cdyn), lung resistance (RL), paO2 and paCO2 were analyzed for 6 h post-inhalation (acute effects 0–2 h; delayed effects 2–6 h). All parameters remained within physiologically normal ranges over the entire observation period. It was concluded that liposomes delivered by the pulmonary route act as local sustained release reservoir, and are safe and nonirritating to the lung.
    International Journal of Pharmaceutics 11/1992; 87(1-3-87):183-193. DOI:10.1016/0378-5173(92)90242-T · 3.79 Impact Factor
  • M. Ausborn, P. Nuhn, H. Schreier

Publication Stats

151 Citations
37.35 Total Impact Points


  • 2004–2008
    • Novartis
      Bâle, Basel-City, Switzerland
  • 1994–2008
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 1995
    • Vanderbilt University
      • Department of Medicine
      Nashville, Michigan, United States