In Vivo Characterization of Biodegradable Drug Delivery Systems

Mader, Karsten

Abstract

To follow the processes of drug delivery and degradation of the delivery device in vivo noninvasively by EPR and MRI.
The aim of the study is to characterize the mechanisms underlying drug delivery (bulk hydrolysis vs. surface erosion) and to find out the reasons for the differences of in vivo/in vitro studies. The current studies cover a broad range of biodegradable polymers used for dr ug delivery devices which are on the market (polylactide-co-glycolide) or are FDA approved for studies on humans (polyanhydrides such as PCCPP-SA) or P(FAD-SA). By means of EPR it is possible to obtain information concerning microviscosity , micropolarity and pH value of the implant in vivo. MRI is used to charact erize the water penetration and changes in the form of the tablet.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Center for Research Resources (NCRR)
• Type: Biotechnology Resource Grants (P41)
• Project #: 2P41RR001811-11
• Application #: 5223642
• Support Year: 11
• Fiscal Year: 1996

Publications

Hurth, Kyle M; Nilges, Mark J; Carlson, Kathryn E et al. (2004) Ligand-induced changes in estrogen receptor conformation as measured by site-directed spin labeling. Biochemistry 43:1891-907

Denisov, Ilia G; Makris, Thomas M; Sligar, Stephen G (2002) Formation and decay of hydroperoxo-ferric heme complex in horseradish peroxidase studied by cryoradiolysis. J Biol Chem 277:42706-10

Woodmansee, Anh N; Imlay, James A (2002) Reduced flavins promote oxidative DNA damage in non-respiring Escherichia coli by delivering electrons to intracellular free iron. J Biol Chem 277:34055-66

Atsarkin, V A; Demidov, V V; Vasneva, G A et al. (2001) Mechanism of oxygen response in carbon-based sensors. J Magn Reson 149:85-9

Mangels, M L; Harper, A C; Smirnov, A I et al. (2001) Investigating magnetically aligned phospholipid bilayers with EPR spectroscopy at 94 GHz. J Magn Reson 151:253-9

Breitzer, J G; Smirnov, A I; Szczepura, L F et al. (2001) Redox properties of C6S8(n-) and C3S5(n-) (n = 0, 1, 2): stable radicals and unusual structural properties for C-S-S-C bonds. Inorg Chem 40:1421-9

Denisov, I G; Hung, S C; Weiss, K E et al. (2001) Characterization of the oxygenated intermediate of the thermophilic cytochrome P450 CYP119. J Inorg Biochem 87:215-26

Kirkor, E S; Scheeline, A (2000) Nicotinamide adenine dinucleotide species in the horseradish peroxidase-oxidase oscillator. Eur J Biochem 267:5014-22

Rapoport, N; Smirnov, A I; Pitt, W G et al. (1999) Bioreduction of Tempone and spin-labeled gentamicin by gram-negative bacteria: kinetics and effect of ultrasound. Arch Biochem Biophys 362:233-41

Maringanti, S; Imlay, J A (1999) An intracellular iron chelator pleiotropically suppresses enzymatic and growth defects of superoxide dismutase-deficient Escherichia coli. J Bacteriol 181:3792-802