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Abstract

Genipin Crosslinked Chitosan Reinforced Apatite Cement as a Carrier for Local Anti-Inflammatory Drug Delivery †

1
Department of Materials and Ceramic Engineering, Aveiro Institute of Materials (CICECO), University of Aveiro, 3810-193 Aveiro, Portugal
2
Department of Chemistry, Aveiro Institute of Materials (CICECO), University of Aveiro, 3810-193 Aveiro, Portugal
3
Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal
*
Authors to whom correspondence should be addressed.
Presented at the Materiais 2022, Marinha Grande, Portugal, 10–13 April 2022.
Mater. Proc. 2022, 8(1), 134; https://doi.org/10.3390/materproc2022008134
Published: 15 July 2022
(This article belongs to the Proceedings of MATERIAIS 2022)
The development of bone substitute materials containing therapeutically active agents is an attractive and useful tool for treating bone loss and inflammation associated with musculoskeletal diseases. In this context, calcium phosphate-based materials, including cements widely used to repair bone tissue, can also be a valuable carrier for local drug delivery. However, poor mechanical properties limit their load-bearing applications. In this work, the effects of incorporation of (1) a small amount of chitosan (CH) in the absence and presence of genipin (G) and (2) a diclofenac mass fraction of 2.5 wt% (DCF, a non-steroidal anti-inflammatory drug) in α-TCP-based apatite cement composition with a liquid-to-powder mass ratio (LPR) of 0.33 were investigated. For this purpose, compressive strength, phase composition, microstructure, porosity, pore-size distribution, the DCF distribution throughout the cement, and in vitro DCF release profiles and kinetics at two different pH values (7.4 and 5.5) were evaluated. The addition of CH/G increased the compressive strength from 40 ± 5 to 58 ± 7 MPa. The presence of DCF together with these additives slightly decreased the compressive strength value to 54 ± 4 MPa. The amount of DCF released after 21 days at pH 7.4 decreases from 34.6 ± 3.7 % to 19.1 ± 2.7 % for the calcium phosphate cement matrix in the absence and presence of the CH/G, respectively. The formulations containing CH/G and CH/G/DCF were selected for further study of the effects of LPR increase (0.40 and 0.45) under the same conditions. The results indicated that the presence of CH/G in α-TCP-based apatite cement mainly changes the porosity, pore size distribution and the phases formed in the setting reaction, which in turn affect the mechanical properties and the drug release profiles.

Author Contributions

Conceptualization: P.M.C.T., A.F.B. and L.G.; methodology: M.A.M., J.O., P.Z., L.M., S.O., L.G., A.F.B. and P.M.C.T.; data curation: M.A.M., J.O., P.Z., L.G, A.F.B. and P.M.C.T.; resources: P.M.C.T., S.O., L.M., A.F.B. and L.G.; supervision: P.M.C.T., A.F.B., L.G.; writing—original draft preparation: P.M.C.T., A.F.B. and M.A.M.; writing—review and editing: P.M.C.T., A.F.B., P.Z. and S.O.; project administration: P.M.C.T., S.O. and A.F.B.; funding acquisition: P.M.C.T., S.O., L.M., A.F.B. and L.G. All authors have read and agreed to the published version of the manuscript.

Funding

This work is funded by FEDER funds through the COMPETE 2020 Program and National Funds through FCT—Portuguese Foundation for Science and Technology under the projects FlexMicroDerm (POCI-01-0145-FEDER-029274) and 2BBone (POCI-01-0145-FEDER-029940). This work was also developed within the scope of the projects of iMed.ULisboa, UIDB/04138/2020 and UIDP/04138/2020, and CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). P. M. C. Torres, S. Olhero and L. Gonçalves acknowledge FCT for CEECIND/01891/2017 and CEECIND/03393/2017 and CEECIND/03143/2017 contracts, respectively.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding authors.

Conflicts of Interest

The authors declare no conflict of interest.
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Share and Cite

MDPI and ACS Style

Martins, M.A.; Oliveira, J.; Zelenovskii, P.; Mafra, L.; Olhero, S.; Gonçalves, L.; Bettencourt, A.F.; Torres, P.M.C. Genipin Crosslinked Chitosan Reinforced Apatite Cement as a Carrier for Local Anti-Inflammatory Drug Delivery. Mater. Proc. 2022, 8, 134. https://doi.org/10.3390/materproc2022008134

AMA Style

Martins MA, Oliveira J, Zelenovskii P, Mafra L, Olhero S, Gonçalves L, Bettencourt AF, Torres PMC. Genipin Crosslinked Chitosan Reinforced Apatite Cement as a Carrier for Local Anti-Inflammatory Drug Delivery. Materials Proceedings. 2022; 8(1):134. https://doi.org/10.3390/materproc2022008134

Chicago/Turabian Style

Martins, Manuel A., Joana Oliveira, Pavel Zelenovskii, Luís Mafra, Susana Olhero, Lídia Gonçalves, Ana F. Bettencourt, and Paula M. C. Torres. 2022. "Genipin Crosslinked Chitosan Reinforced Apatite Cement as a Carrier for Local Anti-Inflammatory Drug Delivery" Materials Proceedings 8, no. 1: 134. https://doi.org/10.3390/materproc2022008134

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