Micelle carriers based on dendritic macromolecules containing bis-MPA and glycine for antimalarial drug delivery

Research output: Contribution to journalArticle

Researchers

  • Elisabet Martí Coma-Cros
  • Alexandre Lancelot
  • María San Anselmo
  • Livia Neves Borgheti-Cardoso
  • Juan José Valle-Delgado

  • José Luis Serrano
  • Xavier Fernàndez-Busquets
  • Teresa Sierra

Research units

  • Barcelona Institute of Science and Technology (BIST)
  • Hospital Clínic-Universitat de Barcelona
  • University of Barcelona
  • University of Zaragoza

Abstract

Biomaterials for antimalarial drug transport still need to be investigated in order to attain nanocarriers that can tackle essential issues related to malaria treatment, e.g. complying with size requirements and targeting specificity for their entry into Plasmodium-infected red blood cells (pRBCs), and limiting premature drug elimination or drug resistance evolution. Two types of dendritic macromolecule that can form vehicles suitable for antimalarial drug transport are herein explored. A new hybrid dendritic-linear-dendritic block copolymer based on Pluronic® F127 and amino terminated 2,2′-bis(glycyloxymethyl)propionic acid dendrons with a poly(ester amide) skeleton (HDLDBC-bGMPA) and an amino terminated dendronized hyperbranched polymer with a polyester skeleton derived from 2,2′-bis(hydroxymethyl)propionic acid (DHP-bMPA) have provided self-assembled and unimolecular micelles. Both types of micelle carrier are biocompatible and exhibit appropriate sizes to enter into pRBCs. Targeting studies have revealed different behaviors for each nanocarrier that may open new perspectives for antimalarial therapeutic approaches. Whereas DHP-bMPA exhibits a clear targeting specificity for pRBCs, HDLDBC-bGMPA is incorporated by all erythrocytes. It has also been observed that DHP-bMPA and HDLDBC-bGMPA incorporate into human umbilical vein endothelial cells with different subcellular localization, i.e. cytosolic and nuclear, respectively. Drug loading capacity and encapsulation efficiencies for the antimalarial compounds chloroquine, primaquine and quinacrine ranging from 30% to 60% have been determined for both carriers. The resulting drug-loaded nanocarriers have been tested for their capacity to inhibit Plasmodium growth in in vitro and in vivo assays.

Details

Original languageEnglish
Pages (from-to)1661-1674
Number of pages14
JournalBiomaterials Science
Volume7
Issue number4
Publication statusPublished - 1 Apr 2019
MoE publication typeA1 Journal article-refereed

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