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

Martí Coma-Cros, E. ; Lancelot, A. ; San Anselmo, M. (Universidad de Zaragoza) ; Neves Borgheti-Cardoso, L. ; Valle-Delgado, J.J. ; Serrano, J.L. (Universidad de Zaragoza) ; Fernàndez-Busquets, X. ; Sierra, T. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1039/c8bm01600c

Año: 2019

Publicado en: Biomaterials science 7, 4 (2019), 1661-1674
ISSN: 2047-4830

Factor impacto JCR: 6.183 (2019)

Categ. JCR: MATERIALS SCIENCE, BIOMATERIALS rank: 6 / 38 = 0.158 (2019) - Q1 - T1

Factor impacto SCIMAGO: 1.437 - Materials Science (miscellaneous) (Q1) - Biomedical Engineering (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/FSE
Financiación: info:eu-repo/grantAgreement/EC/H2020/712754/EU/Postdoctoral Programme in Bioengineering Excellence Scientific Training/BEST
Financiación: info:eu-repo/grantAgreement/ES/MCIU-FEDER/BIO2014-52872-R
Financiación: info:eu-repo/grantAgreement/ES/MCIU-FEDER/CTQ2015-70174-P
Financiación: info:eu-repo/grantAgreement/ES/MCIU-FEDER/MAT2015-66208-C3-1-P
Financiación: info:eu-repo/grantAgreement/ES/MCIU/FPU12-05210
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SEV-2014-0425

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)