Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil

Antonio Di Martino, Pavel Kucharczyk, Zdenka Capakova, Petr Humpolicek, Vladimir Sedlarik

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs – doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120–200 nm and 20–37 mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24 h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers.

Original languageEnglish
Pages (from-to)613-624
Number of pages12
JournalInternational Journal of Biological Macromolecules
Volume102
DOIs
Publication statusPublished - 1 Sep 2017
Externally publishedYes

Keywords

  • 5-Fluorouracil
  • Burst effect
  • Chitosan
  • Doxorubicin
  • Drug delivery
  • Polycomplexes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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