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Int. J. Mol. Sci. 2018, 19(8), 2310; https://doi.org/10.3390/ijms19082310

Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

1
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
2
Clinica di Malattie del Apparato Respiratorio, IRCCS Fondazione S. Matteo, via Golgi 19, 27100 Pavia, Italy
3
Department of Molecular Medicine, Pneumology Unit, University of Pavia, Viale Golgi, 19, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Received: 10 July 2018 / Revised: 2 August 2018 / Accepted: 3 August 2018 / Published: 7 August 2018
(This article belongs to the Special Issue Smart Polymers for Biomedical Applications)
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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. View Full-Text
Keywords: hyaluronic acid; everolimus; polysaccharides nanoparticles; ionotropic gelification; CD44-targeting; bronchiolitis obliterans syndrome hyaluronic acid; everolimus; polysaccharides nanoparticles; ionotropic gelification; CD44-targeting; bronchiolitis obliterans syndrome
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Chiesa, E.; Dorati, R.; Conti, B.; Modena, T.; Cova, E.; Meloni, F.; Genta, I. Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus. Int. J. Mol. Sci. 2018, 19, 2310.

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