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Synthesis of Poly(ester amide) Microparticles for Intra-articular drug delivery Ian Villamagna, Frank Beier, Elizabeth R. Gillies University of Western Ontario—Department of Biomedical Engineering Statement of Purpose: To fabricate and characterize degradation. In addition to release profiles, particle poly(ester amide) microparticles that can be used in intradegradation was monitored through SEM imaging and articular injections for the localized treatment of showed the erosion of particles that is consistent with the Osteoarthritis (OA). release of celocoxib measured by UV-visible Introduction: Osteoarthritis is a debilitating and spectroscopy. An MTT assay, performed on ATDC5 cells degenerative multifaceted joint disorder that affects over to mimic cell interactions in the intra-articular space 10 million American adults over the age of 45, and is the showed no significant cell toxicity to the material, leading cause of disability in this age group.1,2 Despite the poly(ester amide), in particle form (n=9). ANOVA was prevalence of the disease, there is currently no known used to compare the treatment groups to control and cure, or disease modifying agent available to treat OA. In determine no significant cell death from treatment with 2015, work from the Beier lab at UWO looked at the role the material. of PPARd in OA, and determined that PPARd inhibitors could be a significant new target therapeutic in the treatment of OA.3While these inhibitors exist they are extremely hydrophobic in nature, and cause multiple side effects, limiting their ability to be used in a systemic delivery fashion. To combat the difficulty in delivery of these sorts of molecules, poly(ester amide) microparticles have been synthesized and characterized. These particles are used to encapsulate the PPARd inhibitor, and due to the amide and ester bonds in the polymer backbone, allows for a slow release of the drug through hydrolysis in the body. Methods: Poly(ester amide)s that had been previously Figure 1. Scanning electron micrograph of Poly(ester amide) studied in the Gillies lab were used in this study.4 microparticles loaded with celocoxib. Particles were found to Microparticles were fabricated through an oil in water have an average size of roughly 1 micron. Visual results were emulsion using poly(vinyl alcohol) as a surfactant in the confirmed with dynamic light scatter. continuous phase. Particles were centrifuged to remove excess surfactant and drug, and lyophilized to form a final Conclusions: This study has shown that hydrophobic product. Size analysis of the particles was performed drugs such as celocoxib, and more novel drugs such as the through dynamic light scatter (DLS). Scanning electron PPARd inhibitor GSK3787 can be successfully microscopy was used to authenticate the DLS as well as encapsulated and released from PEA microparticles. The to view surface characteristics and morphology. initial studies performed to characterize the material, Encapsulation efficiency and drug loading for the including cell toxicity and drug release studies, give a particles were calculated. Release studies from the strong indication of its usefulness in a physiological microparticles were performed with Celocoxib as a model setting. Future work with these particles has been planned drug, prior to the incorporation and release studies with and will include further in vitro testing with GSK3787 GSK3787. Cell toxicity of blank poly(ester amide) release, explant tissue studies, and in vivo studies. The particles was performed through an MTT assay using current study shows a new method to successfully ATDC5 cells. encapsulate and release novel and potentially disease Results: Particles were synthesized and characterized as modifying drugs to treat OA. described above. Microparticles were found to have an References: average size of ~1.0 microns by DLS. SEM imaging 1. Sharif B. Osteoarthr Cartil. 2016:1-10. shows uniform spherical particles with little to no surface 2. Hunter DJ. Nat Rev Rheumatol. 2014;10(7):437defects. Encapsulation efficiency of celocoxib loaded 441. microparticles was found to be 92% with a drug loading 3. Ratneswaran A. Arthritis Rheumatol. of 33%. Encapsulation efficiency of GSK 3787 loaded 2015;67(2):454-464. microparticles was found to be 93% while drug loading 4. Moustafa A. Can J Chem Eng. 2015;93(12):2098percentage was determined to be 29%, showing that 2106. multiple hydrophobic drugs can be encapsulated. Release studies of a model drug from the polymer particles agrees with data from previously completed degradation studies on the polymer. A slow, continuous release was observed in particles; after 7 days of release an average of 15% of the loaded drug had been released from the particles with bulk erosion of the particles the most likely method of