XPS and TOF-SIMS microanalysis of a peptide/polymer drug delivery device.
The localization of a peptide drug dispersed in a solid matrix of hydroxypropyl cellulose (HPC) was determined at micrometer lateral resolution using secondary ion mass spectrometry (SIMS)/ion microscopy. Leuprolide formulated as a sustained release drug delivery device has been selected as a model compound for this investigation. One key facet of this study was to attempt to understand the distribution and ultimate bioavailability of the peptide dispersed in an inert polymer matrix. The results reported in this paper demonstrate that the lateral distribution of leuprolide along the surfaces of cross sections prepared from different polymer formulations is different. Ion microscopy directly measures the lateral distribution of protonated molecular ions as well as specific fragment peaks and provides a direct method of determining peptide distributions in polymers. Ion images of leuprolide dispersed in HPC demonstrate that the peptide distribution is critically dependent on polymer composition. The mass spectrometry results augment quantitative X-ray photoelectron (XPS) measurement of C and N levels in different polymer/peptide formulations. The combination of XPS and TOF-SIMS techniques provides a powerful method for determining the distribution of peptides in polymer matrices.
John
C M
CM
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
Odom
R W
RW
Salvati
L
L
Annapragada
A
A
Fu Lu
M Y
MY
D000595:Amino Acid Sequence; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004577:Electron Probe Microanalysis; D016729:Leuprolide / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D011108:Polymers
D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D010455:Peptides; D011108:Polymers; D002482:Cellulose; C008079:hydroxypropylcellulose; D016729:Leuprolide