Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy

Area of Science:

• Biomaterials Science
• Spectroscopy
• Drug Delivery Systems

Background:

• Hydrogels, derived from natural or synthetic sources, are extensively researched for implant and payload carrier applications.
• Nanofibrillated cellulose (NFC) hydrogels, including anionic variants (ANFC), offer potential for immediate and controlled drug release due to slow drug dissolution.
• Raman spectroscopy is valuable for analyzing hydrogels due to its water insensitivity, enabling label-free, real-time drug release studies.

Purpose of the Study:

• To develop and validate a novel, label-free Raman spectroscopy technique for investigating drug diffusion in ANFC hydrogels.
• To overcome the limitations of traditional Raman spectroscopy, such as strong fluorescence backgrounds that mask faint Raman signals.
• To demonstrate the capability of this method for real-time, quantitative analysis of drug release kinetics.

Main Methods:

• Utilized a specialized Raman spectrometer combining a pulsed laser and time-resolved CMOS SPAD sensor to suppress fluorescence.
• Investigated the diffusion of Metronidazole and Vitamin C within ANFC hydrogels.
• Employed time-resolved Raman and fluorescence spectroscopy for comprehensive sample analysis.

Main Results:

• Successfully demonstrated label-free, real-time investigation of Metronidazole and Vitamin C diffusion in ANFC.
• Showcased the ability to modulate ANFC-based implant and drug delivery systems by controlling release rates.
• Validated the universality of the developed method for various hydrogel/drug combinations.

Conclusions:

• The developed time-resolved Raman spectroscopy method provides a universal platform for accurate, real-time drug diffusion coefficient determination in complex hydrogel systems.
• This technique overcomes limitations of traditional sampling methods and fluorescence interference, offering significant advancements for biomaterial and drug delivery research.
• The combined time-resolved Raman and fluorescence analysis yields additional insights into chemical and structural changes within the samples.