Bone-targeting polyphosphodiesters that promote osteoblastic differentiation.


Journal

Journal of biomedical materials research. Part A
ISSN: 1552-4965
Titre abrégé: J Biomed Mater Res A
Pays: United States
ID NLM: 101234237

Informations de publication

Date de publication:
05 2023
Historique:
revised: 15 12 2022
received: 26 09 2022
accepted: 30 12 2022
pubmed: 10 1 2023
medline: 22 3 2023
entrez: 9 1 2023
Statut: ppublish

Résumé

Polymers for pharmaceutical use have been attractive in medical treatments because of the conjugation of multifunctional components and their long circulation time in the blood stream. Bone-targeted drug delivery systems are also no exceptional, and several polymers have been proposed for the treatment of bone diseases, such as cancer metastasis and osteoporosis. Herein, we report that polyphosphodiesters (PPDEs) have a potential to enhance osteoblastic differentiation, and they have a targeting ability to bone tissues in vivo. Two types of PPDEs, poly (ethylene sodium phosphate) (PEP•Na) and poly (propylene sodium phosphate) (PPP•Na), have been synthesized. Regardless of the alkylene structure in the main chain of PPDEs, the gene expression of osteoblast-specific transcription factors and differentiation markers of mouse osteoblastic-like cells (MC3T3-E1 cells) cultured in a differentiation medium was significantly upregulated by the addition of PPDEs. Moreover, it was also clarified that the signaling pathway related to cytoplasmic calcium ions was activated by PPDEs. The mineralization of MC3T3-E1 cells has a similar trend with its gene expression and is synergistically enhanced by PPDEs with β-glycerophosphate. The biodistribution of fluorescence-labeled PPDEs was also determined after intravenous injection in mice. PPDEs accumulated well in the bone through the blood stream, whereas polyphosphotriesters (PPTEs) tended to be excreted from the kidneys. Hydrophilic PEP•Na showed a superior bone affinity as compared with PPP•Na. PPDEs could be candidate polymers for the restoration of bone remodeling and bone-targeting drug delivery platforms.

Identifiants

pubmed: 36622032
doi: 10.1002/jbm.a.37499
doi:

Substances chimiques

sodium phosphate SE337SVY37

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

714-724

Subventions

Organisme : Japan Society for the Promotion of Science
ID : #19H04474

Informations de copyright

© 2023 Wiley Periodicals LLC.

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Auteurs

Kenjiro Kiyono (K)

Department of Chemistry and Materials Engineering, Kansai University, Suita-shi, Osaka, Japan.

Shun Mabuchi (S)

Department of Chemistry and Materials Engineering, Kansai University, Suita-shi, Osaka, Japan.

Akihisa Otaka (A)

Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita-shi, Osaka, Japan.
ORDIST, Kansai University, Suita-shi, Osaka, Japan.

Yasuhiko Iwasaki (Y)

Department of Chemistry and Materials Engineering, Kansai University, Suita-shi, Osaka, Japan.
ORDIST, Kansai University, Suita-shi, Osaka, Japan.

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