1. Multimodal imaging of drug and excipients in rat lungs following an inhaled administration of controlled-release drug laden PLGA microparticles
- Author
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Brian Farrer, Eve Robinson, Joseph Marchand, Ian S. Gilmore, Meredith Earl, Rasmus Havelund, Diane M. Coe, Doug Ball, Dave Hassall, Simon Teague, Heather Reid, Rebecca Terry, Paul Giffen, and Peter S. Marshall
- Subjects
Drug ,media_common.quotation_subject ,Context (language use) ,Multimodal Imaging ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,Excipients ,Delayed-Action Preparations ,03 medical and health sciences ,Therapeutic index ,Electrochemistry ,Animals ,Environmental Chemistry ,Distribution (pharmacology) ,Medicine ,Particle Size ,Microparticle ,Lung ,Spectroscopy ,030304 developmental biology ,media_common ,0303 health sciences ,business.industry ,010401 analytical chemistry ,Controlled release ,Rats ,0104 chemical sciences ,Drug delivery ,business ,Biomedical engineering - Abstract
Controlled-release formulations, in the form of micro- or nanoparticles, are increasingly attractive to the pharmaceutical industry for drug delivery. For respiratory illnesses, controlled-release microparticle formulations provide an opportunity to deliver a higher percentage of an inhaled medicament dose to the lung, thus potentially reducing the therapeutic dose, frequency of dosing, and minimising side-effects. We describe the use of a multimodal approach consisting of MALDI MS imaging, 3D depth profiling TOF-SIMS analysis, and histopathology to monitor the distribution of drug and excipients in sections taken from excised rat lungs following an inhaled administration of drug-laden microparticles. Following a single dose, the administered drug was detected in the lung via both MALDI MS and TOF-SIMS over a range of time points. Both imaging techniques enabled the characterisation of the distribution and retention of drug particles and identified differences in the capabilities of both imaging modalities. Histochemical staining of consecutive sections was used to provide biological context to the findings and will also be discussed in this presentation. We demonstrate how this multimodal approach could be used to help increase our understanding of the use of controlled release microparticles.
- Published
- 2021