University of Oulu

Jacopo Zini, Jere Kekkonen, Ville A. Kaikkonen, Timo Laaksonen, Pekka Keränen, Tuomo Talala, Anssi J. Mäkynen, Marjo Yliperttula, Ilkka Nissinen, Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy, Journal of Controlled Release, Volume 334, 2021, Pages 367-375, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.04.032

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

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Author: Zini, Jacopo1; Kekkonen, Jere2; Kaikkonen, Ville A.3;
Organizations: 1Division of Pharmaceutical Biosciences, Drug Research Program, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
2Circuits and Systems Research Unit, University of Oulu, 90014 Oulu, Finland
3Optoelectronics and Measurement Techniques Research Unit, University of Oulu, 90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021053132251
Language: English
Published: Elsevier, 2021
Publish Date: 2021-05-31
Description:

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) single-photon 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.

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Series: Journal of controlled release
ISSN: 0168-3659
ISSN-E: 1873-4995
ISSN-L: 0168-3659
Volume: 334
Pages: 367 - 375
DOI: 10.1016/j.jconrel.2021.04.032
OADOI: https://oadoi.org/10.1016/j.jconrel.2021.04.032
Type of Publication: A1 Journal article – refereed
Field of Science: 213 Electronic, automation and communications engineering, electronics
3111 Biomedicine
317 Pharmacy
Subjects:
Funding: This work was supported by the Academy of Finland grants n:o 314406 (MY), n:o 314404 (IN), n:o 323719 (IN), n:o 314405 (AM).
Academy of Finland Grant Number: 314404
323719
314405
Detailed Information: 314404 (Academy of Finland Funding decision)
323719 (Academy of Finland Funding decision)
314405 (Academy of Finland Funding decision)
Copyright information: © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  https://creativecommons.org/licenses/by/4.0/