Noninvasive in Vivo Monitoring of Drug Release and Polymer Erosion from Biodegradable Polymers by EPR Spectroscopy and NMR Imaging

Karsten Mäder, Goran Bacic, Abraham Domb, Omar Elmalak, Robert Langer, Harold M. Swartz

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Biodegradable polymers have attracted much attention as implantable drug delivery systems. Uncertainty in extrapolating in vitro results to in vivo systems due to the difficulties of appropriate characterization in vivo, however, is a significant issue in the development of these systems. To circumvent this limitation, noninvasive magnetic resonance techniques, electron paramagnetic resonance (EPR) and magnetic resonance imaging (MRI), were applied to characterize drug release and polymer degradation in vitro and in vivo. MRI makes it possible to monitor water content, tablet shape, and response of the biological system such as edema and encapsulation. The results of the MRI experiments give the first direct proof in vivo of postulated mechanisms of polymer erosion, Using nitroxide radicals as model drug releasing compounds, information on the mechanism of drug release and microviscosity inside the implant can be obtained by means of 1.2 GHz EPR spectroscopy. To be able to attribute nitroxide mobility to a particular layer of the implant, sandwich-like tablets were manufactured, taking advantage of the distinct spectral features of nitroxides containing different isotopes of nitrogen (15N vs 14N). The use of both noninvasive methods to monitor processes in vivo leads to new insights in understanding the mechanisms of drug release and polymer degradation.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume86
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

Bibliographical note

Funding Information:
We thank Prof. J. Dunn, Dartmouth Medical School, for the use of the MRI facilities of his laboratory, and Boehringer Ingelheim, Germany, for the gift of the PLGA. K.M. gratefully acknowledges his support from Deutscher Akademischer Austauschdienst (DAAD). This research used the facilities of the EPR Center at Dartmouth and was supported by NIH Grants RR 01811 and NCDDG CA52857-06.

Funding

We thank Prof. J. Dunn, Dartmouth Medical School, for the use of the MRI facilities of his laboratory, and Boehringer Ingelheim, Germany, for the gift of the PLGA. K.M. gratefully acknowledges his support from Deutscher Akademischer Austauschdienst (DAAD). This research used the facilities of the EPR Center at Dartmouth and was supported by NIH Grants RR 01811 and NCDDG CA52857-06.

FundersFunder number
NCDDGCA52857-06
National Institutes of HealthRR 01811
National Cancer InstituteU19CA052857
Deutscher Akademischer Austauschdienst

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