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

Matthew J. Owen, Jasper H.N. Yik, Congwang Ye, Brianca Netto, Dominik R. Haudenschild, Gang yu Liu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1116-1124
Number of pages9
JournalChemical Research in Chinese Universities
Volume37
Issue number5
DOIs
StatePublished - Oct 2021

Keywords

  • Flavopiridol
  • Green solvent
  • Local sustained release
  • Microfluidics
  • Poly(lactic-co-glycolic acid) microparticle

ASJC Scopus subject areas

  • Chemistry(all)

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