Hyaluronic acid-decorated chitosan nanoparticles for CD44-targeted delivery of everolimus

Enrica Chiesa, Rossella Dorati, Bice Conti, Tiziana Modena, Emanuela Cova, Federica Meloni, Ida Genta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (≤200 nm), minimizing the size polydispersity (PDI 0.171 ± 0.04), and at the negative ζ potential maximization (−30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 ± 13.68 µg/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37° C and 4° C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.

Original languageEnglish
Article number2310
JournalInternational Journal of Molecular Sciences
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 7 2018

Fingerprint

Hyaluronic acid
Chitosan
Hyaluronic Acid
Nanoparticles
delivery
nanoparticles
acids
Allografts
lungs
Bronchiolitis Obliterans
cells
rejection
Lung
Ionotropic gelation
factorial design
experiment design
Cell proliferation
Cell growth
Polydispersity
gelation

Keywords

  • Bronchiolitis obliterans syndrome
  • CD44-targeting
  • Everolimus
  • Hyaluronic acid
  • Ionotropic gelification
  • Polysaccharides nanoparticles

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Hyaluronic acid-decorated chitosan nanoparticles for CD44-targeted delivery of everolimus. / Chiesa, Enrica; Dorati, Rossella; Conti, Bice; Modena, Tiziana; Cova, Emanuela; Meloni, Federica; Genta, Ida.

In: International Journal of Molecular Sciences, Vol. 19, No. 8, 2310, 07.08.2018.

Research output: Contribution to journalArticle

Chiesa, Enrica ; Dorati, Rossella ; Conti, Bice ; Modena, Tiziana ; Cova, Emanuela ; Meloni, Federica ; Genta, Ida. / Hyaluronic acid-decorated chitosan nanoparticles for CD44-targeted delivery of everolimus. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 8.
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