A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol

doi:10.1007/s40242-021-1262-8

Chemical Research in Chinese Universities ›› 2021, Vol. 37 ›› Issue (5): 1116-1124.doi: 10.1007/s40242-021-1262-8

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A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol

Matthew J. OWEN¹, Jasper H. N. YIK², Congwang YE³, Brianca NETTO¹, Dominik R. HAUDENSCHILD², Gang-yu LIU¹

1. Department of Chemistry, University of California, One Shields Avenue, Davis, California, 95616, United States;
2. Department of Orthopedic Surgery, University of California-Davis School of Medicine, 4635 Second Ave., Sacramento, California, 95817, United States;
3. Materials Engineering Division, Lawrence Livermore National Laboratory, Livermore, California, 94550, United States

Received:2021-07-09 Revised:2021-08-06 Online:2021-10-01 Published:2021-08-19
Contact: Gang-yu LIU, Dominik R. HAUDENSCHILD E-mail:gyliu@ucdavis.edu;drhaudenschild@ucdavis.edu
Supported by:
This work was supported by the DOD(CDMRP Award PR171305) and UC Davis. We thank Dr. Arpad KARSAI, Professor Jamal LEWIS, Ms. Audrey SULKANEN, and Ms. Minyuan WANG for helpful discussions. We also thank Professor Xi CHEN and Dr. Hai YU for their technical assistance in post synthesis treatments.

Abstract

Abstract: Poly(lactic-co-glycolic acid)(PLGA) microparticles represent an important class of materials used for drug delivery. Current synthesis frequently uses conventional emulsion, where dichloromethane(DCM) is used as the organic phase solvent. Due to the health and environmental toxicity of DCM and its slow degradation, this work replaces DCM with a greener solvent, dimethyl carbonate(DMC). To attain narrow distribution of PLGA particle size, microfluidic flow focusing was chosen over conventional emulsion. This new approach successfully produced PLGA microparticles encapsulated with flavopiridol, a kinase inhibitor. These particles exhibit sustained release profile more desirable than the conventional counterparts. The cytotoxicity and activity tests have demonstrated high biocompatibility and efficacy of these PLGA particles. The high sustainability is also evaluated using simple E-Factor(sEF) and complete E-Factor(cEF). The lower health and environmental toxicities of DMC than DCM are evidenced by approximately one order of magnitude higher in lethal dose, i. e., 50%(LD₅₀) values in rat, 5-fold faster degradation rate, and 30% higher GlaxoSmithKline(GSK) combined greenness value. The approach reported in this work shall provide a new and green means for drug delivery in general. The products enable local sustained delivery of flavopiridol for prevention of post-traumatic osteoarthritis, and anti-cancer therapy.

Key words: Flavopiridol, Microfluidics, Poly(lactic-co-glycolic acid) microparticle, Green solvent, Local sustained release

Matthew J. OWEN, Jasper H. N. YIK, Congwang YE, Brianca NETTO, Dominik R. HAUDENSCHILD, Gang-yu LIU. A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol[J]. Chemical Research in Chinese Universities, 2021, 37(5): 1116-1124.

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A Green Approach to Producing Polymer Microparticles for Local Sustained Release of Flavopiridol

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