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Villamagna IJ, McRae DM, Borecki A, et al. GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery. Polymers (Basel). 2020;12(4)doi: 10.3390/polym12040736.
Villamagna, I. J., McRae, D. M., Borecki, A., Mei, X., Lagugné-Labarthet, F., Beier, F., & Gillies, E. R. (2020). GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery. Polymers, 12(4), . https://doi.org/10.3390/polym12040736
Villamagna, Ian J, et al. "GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery." Polymers vol. 12,4 (2020). doi: https://doi.org/10.3390/polym12040736
Villamagna IJ, McRae DM, Borecki A, Mei X, Lagugné-Labarthet F, Beier F, Gillies ER. GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery. Polymers (Basel). 2020 Mar 26;12(4). doi: 10.3390/polym12040736. PMID: 32224867; PMCID: PMC7240550.
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Polymers (Basel). 2020 Mar 26;12(4). doi: 10.3390/polym12040736.

GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery.

Polymers

Ian J Villamagna, Danielle M McRae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth R Gillies

Affiliations

  1. School of Biomedical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada.
  2. Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5B9, Canada.
  3. Department of Chemistry, The University of Western Ontario, London, ON N6A 5B7, Canada.
  4. Department of Physiology and Pharmacology, The University of Western Ontario, London, ON N6A 3B7, Canada.
  5. Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada.

PMID: 32224867 PMCID: PMC7240550 DOI: 10.3390/polym12040736

Abstract

Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young's moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.

Keywords: GSK3787; atomic force microscopy; drug delivery; osteoarthritis; particles; poly(ester amide)

References

  1. Osteoarthritis Cartilage. 2013 Sep;21(9):1145-53 - PubMed
  2. Vet J. 2016 Mar;209:40-9 - PubMed
  3. Chem Soc Rev. 2009 Apr;38(4):1139-51 - PubMed
  4. J Orthop Res. 1991 May;9(3):330-40 - PubMed
  5. Sci Transl Med. 2018 Nov 28;10(469): - PubMed
  6. J Biomed Mater Res B Appl Biomater. 2009 May;89(2):491-500 - PubMed
  7. Ann Rheum Dis. 2015 Jan;74(1):252-9 - PubMed
  8. Jundishapur J Nat Pharm Prod. 2012 Fall;7(4):144-52 - PubMed
  9. J Control Release. 2017 May 10;253:64-72 - PubMed
  10. Pharm Res. 2014 Dec;31(12):3335-47 - PubMed
  11. Arthritis Rheum. 2007 Oct 15;57(7):1211-9 - PubMed
  12. Biomaterials. 2014 Jan;35(1):538-49 - PubMed
  13. Rev Sci Instrum. 2016 Nov;87(11):11E311 - PubMed
  14. Drug Discov Today. 2018 Oct;23(10):1761-1775 - PubMed
  15. Biomaterials. 2014 Sep;35(27):7919-28 - PubMed
  16. Curr Osteoporos Rep. 2016 Dec;14(6):260-268 - PubMed
  17. J Invest Dermatol. 2004 Apr;122(4):971-83 - PubMed
  18. Best Pract Res Clin Rheumatol. 2011 Dec;25(6):801-14 - PubMed
  19. Drug Deliv. 2014 Aug;21(5):342-50 - PubMed
  20. Arthritis Care Res (Hoboken). 2015 Feb;67(2):203-15 - PubMed
  21. Mol Cell Biol. 2007 Oct;27(20):7161-75 - PubMed
  22. PM R. 2012 May;4(5 Suppl):S97-103 - PubMed
  23. J Biomed Mater Res A. 2019 Jun;107(6):1235-1243 - PubMed
  24. J Control Release. 2004 Sep 30;99(2):271-80 - PubMed
  25. J Orthop Res. 1997 Jul;15(4):499-506 - PubMed
  26. J Clin Invest. 2006 Jan;116(1):4-15 - PubMed
  27. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3444-9 - PubMed
  28. Biomacromolecules. 2011 Jul 11;12(7):2475-87 - PubMed
  29. Ann Rheum Dis. 1996 Apr;55(4):211-3 - PubMed
  30. Curr Opin Rheumatol. 2018 Mar;30(2):160-167 - PubMed
  31. J Control Release. 2016 Dec 28;244(Pt A):30-40 - PubMed
  32. Vet J. 2011 Oct;190(1):15-21 - PubMed
  33. Acta Biomater. 2014 Aug;10(8):3484-96 - PubMed
  34. J Med Chem. 2010 Feb 25;53(4):1857-61 - PubMed
  35. Rev Sci Instrum. 2014 Nov;85(11):113703 - PubMed
  36. Cell Transplant. 2015;24(6):1053-66 - PubMed
  37. Artif Cells Nanomed Biotechnol. 2018;46(sup2):152-160 - PubMed
  38. Int J Clin Pract. 2012 Jul;66(7):699-704 - PubMed
  39. Nat Protoc. 2008;3(8):1253-60 - PubMed
  40. J Biomater Sci Polym Ed. 2004;15(1):1-24 - PubMed
  41. Nat Rev Rheumatol. 2015 Jan;11(1):35-44 - PubMed
  42. Int J Pharm. 2013 Jan 30;441(1-2):285-90 - PubMed
  43. Osteoarthritis Cartilage. 2015 Jan;23(1):151-60 - PubMed
  44. Environ Sci Technol. 1976 Dec 1;10(13):1275 - PubMed
  45. Osteoarthritis Cartilage. 2017 Jan;25(1):46-52 - PubMed
  46. PM R. 2012 May;4(5 Suppl):S10-9 - PubMed
  47. PM R. 2012 May;4(5 Suppl):S53-8 - PubMed
  48. Arthritis Rheumatol. 2015 Feb;67(2):454-64 - PubMed
  49. Int J Biochem Cell Biol. 2013 Nov;45(11):2580-4 - PubMed

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