In Situ Imaging of Subcutaneous Drug Delivery Systems Using Microspatially Offset Low-Frequency Raman Spectroscopy

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Materials Science

Background:

• Noninvasive monitoring of subcutaneous implants is crucial for optimizing drug delivery and ensuring therapeutic efficacy.
• Current methods often lack the ability for real-time, in situ assessment of drug retention and implant integrity.

Purpose of the Study:

• To investigate the feasibility of microspatially offset low-frequency Raman spectroscopy (micro-SOLFRS) for nonintrusive, in situ analysis of subcutaneous drug delivery systems.
• To demonstrate the capability of micro-SOLFRS in monitoring drug concentrations and implant status within biological tissues.

Main Methods:

• A proof-of-principle study utilizing caffeine as a model drug embedded in a Soluplus matrix.
• Testing of prototype implants under simulated skin tissue using various caffeine concentrations and micro-SOLFRS displacement settings (Δz = 0-8 mm).
• Optimization of real-time micro-SOLFRS analysis through skin tissue embedded in an agarose hydrogel for pseudo-3D imaging.

Main Results:

• Micro-SOLFRS successfully distinguished temporal and spatial erosion of the implant and solid-state transformations of caffeine.
• Spectrometric results correlated with high-performance liquid chromatography (HPLC) data, accurately reflecting drug dissipation and diffusion.
• Demonstrated the capability for real-time, in situ measurements of drug and implant status through simulated tissue.

Conclusions:

• Micro-SOLFRS is a promising technique for noninvasive, in situ monitoring of subcutaneous drug delivery systems.
• This technology offers potential for optimizing therapeutic regimens and avoiding subtherapeutic drug delivery.
• The findings suggest micro-SOLFRS could lead to the development of new point-of-care diagnostic technologies for biomedical applications.