Chitosan-Hyaluronan Nanoparticles for Vinblastine Sulfate Delivery: Characterization and Internalization Studies on K-562 Cells

Carmela Cannavà; Federica De Gaetano; Rosanna Stancanelli; Valentina Venuti; Giuseppe Paladini; Francesco Caridi; Corneliu Ghica; Vincenza Crupi; Domenico Majolino; Guido Ferlazzo; Silvana Tommasini; Cinzia Anna Ventura

doi:10.3390/pharmaceutics14050942

Chitosan-Hyaluronan Nanoparticles for Vinblastine Sulfate Delivery: Characterization and Internalization Studies on K-562 Cells

Pharmaceutics. 2022 Apr 26;14(5):942. doi: 10.3390/pharmaceutics14050942.

Affiliations

¹ Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Via Consolare Valeria, 1, I-98125 Messina, Italy.
² Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, I-98166 Messina, Italy.
³ Department of Mathematical and Computer Sciences, Physical Sciences and Earth Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, I-98166 Messina, Italy.
⁴ National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania.

Abstract

In the present study, we developed chitosan/hyaluronan nanoparticles (CS/HY NPs) for tumor targeting with vinblastine sulfate (VBL), that can be directed to the CD44 transmembrane receptor, over-expressed in cancer cells. NPs were prepared by coating with HY-preformed chitosan/tripolyphosphate (CS/TPP) NPs, or by polyelectrolyte complexation of CS with HY. NPs with a mean hydrodynamic radius (R_H) of 110 nm, 12% polydispersity index and negative zeta potential values were obtained by a direct complexation process. Transmission Electron Microscopy (TEM) images showed spherical NPs with a non-homogeneous matrix, probably due to a random localization of CS and HY interacting chains. The intermolecular interactions occurring between CS and HY upon NPs formation were experimentally evidenced by micro-Raman (µ-Raman) spectroscopy, through the analysis of the spectral changes of characteristic vibrational bands of HY during NP formation, in order to reveal the involvement of specific chemical groups in the process. Optimized NP formulation efficiently encapsulated VBL, producing a drug sustained release for 20 h. In vitro studies demonstrated a fast internalization of labeled CS/HY NPs (within 6 h) on K-562 human myeloid leukemia cells. Pre-saturation of CD44 by free HY produced a slowing-down of NP uptake over 24 h, demonstrating the need of CD44 for the internalization of HY-based NPs.

Keywords: K-562 cells; chitosan/hyaluronan nanoparticles; in vitro studies; micro-Raman spectroscopy; transmission electron microscopy; vinblastine sulfate.