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

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http://hdl.handle.net/10138/332498

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Zini , J , Kekkonen , J , Kaikkonen , V A , Laaksonen , T , Keränen , P , Talala , T , Mäkynen , A J , Yliperttula , M & Nissinen , I 2021 , ' Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy ' , Journal of Controlled Release , vol. 334 , pp. 367-375 . https://doi.org/10.1016/j.jconrel.2021.04.032

Title: Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy
Author: Zini, Jacopo; Kekkonen, Jere; Kaikkonen, Ville A.; Laaksonen, Timo; Keränen, Pekka; Talala, Tuomo; Mäkynen, Anssi J.; Yliperttula, Marjo; Nissinen, Ilkka
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Pharmaceutical Nanotechnology
University of Helsinki, Division of Pharmaceutical Biosciences
Date: 2021-06-10
Language: eng
Number of pages: 9
Belongs to series: Journal of Controlled Release
ISSN: 0168-3659
URI: http://hdl.handle.net/10138/332498
Abstract: Hydrogels, natural and synthetic origin, are actively studied for their use for implants and payload carriers. These biomaterials for delivery systems have enormous potential in basic biomedical research, drug development, and long-term delivery of biologics. Nanofibrillated cellulose (NFC) hydrogels, both natural and anionic (ANFC) ones, allow drug loading for immediate and controlled release via the slow drug dissolution of solid drug crystals into hydrogel and its subsequent release. This property makes NFC originated hydrogels an interesting non-toxic and non-human origin material as drug reservoir for long-term controlled release formulation or implant for patient care. A compelling tool for studying NFC hydrogels is Raman spectroscopy, which enables to resolve the chemical structures of different molecules in a high-water content like hydrogels, since Raman spectroscopy is insensitive to water molecules. That offers real time investigation of label-free drugs and their release in high-water-content media. Despite the huge potential of Raman spectroscopy in bio-pharmaceutical applications, the strong fluorescence background of many drug samples masking the faint Raman signal has restricted the widespread use of it. In this study we used a Raman spectrometer capable of suppressing the unpleasant fluorescence background by combining a pulsed laser and time-resolved complementary metal-oxide-semiconductor (CMOS) singlephoton avalanche diode (SPAD) line sensor for the label-free investigation of Metronidazole and Vitamin C diffusivities in ANFC. The results show the possibility to modulate the ANFC-based implants and drug delivery systems, when the release rate needs to be set to a desired value. More importantly, the now developed label free real-time method is universal and can be adapted to any hydrogel/drug combination for producing reliable drug diffusion coefficient data in complex and heterogeneous systems, where traditional sampling-based methods are cumbersome to use. The wide temporal range of the time-resolved CMOS SPAD sensors makes it possible to capture also the fluorescence decay of samples, giving rise to a combined time-resolved Raman and fluorescence spectroscopy, which provides additional information on the chemical, functional and structural changes in samples.
Subject: Raman
Fluorescence
Drug diffusion
Label-free
Real-time
Nanofibrillated cellulose hydrogel
Anionic nanofibrillated cellulose hydrogel
DIFFUSION-COEFFICIENTS
SUPPRESSION
317 Pharmacy
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