On-chip synthesis of hyaluronic acid-based nanoparticles for selective inhibition of CD44+ human mesenchymal stem cell proliferation

Enrica Chiesa, Federica Riva, Rossella Dorati, Antonietta Greco, Stefania Ricci, Silvia Pisani, Maddalena Patrini, Tiziana Modena, Bice Conti, Ida Genta

Research output: Contribution to journalArticle

Abstract

In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 - 4.51 nm) and loco-regional (349.15 - 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< -20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis.

Original languageEnglish
Article number260
JournalPharmaceutics
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Cd44 targeting
  • Chitosan
  • Everolimus
  • Human mesenchymal stem cells
  • Hyaluronic acid-based nanocarriers
  • Microfluidics

ASJC Scopus subject areas

  • Pharmaceutical Science

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