M Ausborn

Novartis, Bâle, Basel-City, Switzerland

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Publications (3)19.25 Total impact

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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. · 3.99 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. · 7.63 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. · 7.63 Impact Factor