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J Biomed Mater Res A. 2019 Jun;107(6):1235-1243. doi: 10.1002/jbm.a.36632. Epub 2019 Feb 22.

Poly(ester amide) particles for controlled delivery of celecoxib.

Author information

1
School of Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada.
2
Bone and Joint Institute, The University of Western Ontario, London, Ontario N6A 5B9, Canada.
3
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada.
4
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
5
Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario N6A 3B7, Canada.
6
Department of Chemistry, The University of Western Ontario, London, Ontario N6A 5B7, Canada.

Abstract

Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the particles. Despite minor structural differences, PBSe and POSe exhibited different thermal and mechanical properties, and encapsulation of CXB influenced these properties. PBSe-CXB particles provided a slower release of drug in vitro relative to POSe-CXB. Toxicity studies showed that particles without drug exhibited low toxicity to ATDC5 and C2C12 cells, while the PBSe-CXB particles exhibited concentration-dependent toxicity. Host response to the particles was evaluated in an ovine model. No adverse effects were observed following intra-articular injection and it was observed that the particles diffused into the surrounding tissues. This work shows the importance of structural tuning in PEA delivery vehicles and demonstrates their potential for further development.

KEYWORDS:

celecoxib; drug delivery; intra-articular; particles; poly(ester amide)

PMID:
30698325
DOI:
10.1002/jbm.a.36632

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