University of Oulu

M. Kovalainen, R. Kamakura, J. Riikonen, M. Finnilä, T. Nissinen, J. Rantanen, M. Niemelä, P. Perämäki, M. Mäkinen, K.H. Herzig, V.P. Lehto, Biodegradation of inorganic drug delivery systems in subcutaneous conditions, European Journal of Pharmaceutics and Biopharmaceutics, Volume 122, 2018, Pages 113-125, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2017.10.014

Biodegradation of inorganic drug delivery systems in subcutaneous conditions

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Author: Kovalainen, M.1; Kamakura, R.1; Riikonen, J.2;
Organizations: 1Research Unit of Biomedicine & Biocenter of Oulu, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Finland
2Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, P.O. Box 1627, 70210 Kuopio, Finland
3Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Finland
4Research Unit of Sustainable Chemistry, Faculty of Technology, P.O.Box 3000, FI-90014 University of Oulu, Finland
5Cancer Research and Translational Medicine Research Unit, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Finland
6Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
7Medical Research Center (MRC) and Oulu University Hospital, Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 3.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019102534826
Language: English
Published: Elsevier, 2018
Publish Date: 2019-10-25
Description:

Abstract

Despite extensive efforts to develop delivery systems for oral administration, subcutaneous (s.c.) injection remains the most common way to administer peptide drugs. To limit the number of frequent injections, sustained release systems that are easy to produce, suitable for various drugs, safe and biodegradable are urgently needed. Porous silicon (PSi) has been recognized to be one of the most promising materials for s.c. peptide delivery, but its biodegradation in s.c. tissue has not been studied in vivo, despite extensive in vitro research.

In the present study, differently modified PSi microparticles were injected s.c. in mice, after which the morphology of the particles was thoroughly studied with transmission electron microscopy, micro-computed tomography and X-ray diffraction. Furthermore, histopathology of the s.c. tissue was analyzed to evaluate biocompatibility. To the best of our knowledge, this is the first systematic study which reveals the degradation behavior of various PSi materials in vivo.

The PSi surface chemistry significantly affected the biodegradation rate of the s.c. injected microparticles. The most hydrophobic PSi microparticles with hydrocarbonized surface showed the lowest biodegradation rate while the hydrophilic microparticles, with oxide surface, degraded the fastest. The results from different empirical methods complemented each other to deduce the biodegradation mechanism of the inorganic delivery system, providing useful information for future development of s.c. carriers.

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Series: European journal of pharmaceutics and biopharmaceutics
ISSN: 0939-6411
ISSN-E: 1873-3441
ISSN-L: 0939-6411
Volume: 122
Pages: 113 - 125
DOI: 10.1016/j.ejpb.2017.10.014
OADOI: https://oadoi.org/10.1016/j.ejpb.2017.10.014
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
317 Pharmacy
Subjects:
Funding: The authors thank SIB Labs, University of Eastern Finland for providing laboratory facilities, Virpi Miettinen (UEF), Riitta Vuento (UO), Herkko Pulkkinen (UEF) for excellent technical support. Academy of Finland (#287625) and Finnish Cultural Foundation are acknowledged for funding (MK).
Copyright information: © 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/