TY - JOUR
T1 - Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment
AU - Biosca, Arnau
AU - Cabanach, Pol
AU - Abdulkarim, Muthanna
AU - Gumbleton, Mark
AU - Gómez-Canela, Cristian
AU - Ramírez, Miriam
AU - Bouzón-Arnáiz, Inés
AU - Avalos-Padilla, Yunuen
AU - Borros, Salvador
AU - Fernàndez-Busquets, Xavier
N1 - Funding Information:
This research was funded by the Ministerio de Ciencia, Innovación y Universidades , Spain; grant number RTI2018–094579-B-I00 (which included FEDER funds), by the Secretaria d'Universitats i Recerca of the Departament d'Empresa i Coneixement of the Generalitat de Catalunya , and by the European Social Fund ( 2019 FI_B2 00165 ).
Funding Information:
ISGlobal and IBEC are members of the CERCA Programme, Generalitat de Catalunya. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program ( CEX2018–000806-S ). This research is part of ISGlobal's Program on the Molecular Mechanisms of Malaria which is partially supported by the Fundación Ramón Areces .
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/3/10
Y1 - 2021/3/10
N2 - The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting to Plasmodium falciparum-infected vs. parasite-free red blood cells (74.8%/0.8% respectively), which was maintained upon encapsulation of the lipophilic antimalarial drug curcumin (82.6%/0.3%). The in vitro efficacy of curcumin upon encapsulation was maintained relative to the free compound, with an IC50 around 5 μM. In vivo assays indicated a significantly increased curcumin concentration in the blood of mice one hour after being orally fed PBMA-MESBMA-curcumin in comparison to the administration of free drug (18.7 vs. 2.1 ng/ml, respectively). At longer times, however, plasma curcumin concentration equaled between free and encapsulated drug, which was reflected in similar in vivo antimalarial activities in Plasmodium yoelii yoelii-infected mice. Microscopic analysis in blood samples of fluorescently labeled PBMA-MESBMA revealed the presence of the polymer inside P. yoelii yoelii-parasitized erythrocytes one hour after oral administration to infected animals.
AB - The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting to Plasmodium falciparum-infected vs. parasite-free red blood cells (74.8%/0.8% respectively), which was maintained upon encapsulation of the lipophilic antimalarial drug curcumin (82.6%/0.3%). The in vitro efficacy of curcumin upon encapsulation was maintained relative to the free compound, with an IC50 around 5 μM. In vivo assays indicated a significantly increased curcumin concentration in the blood of mice one hour after being orally fed PBMA-MESBMA-curcumin in comparison to the administration of free drug (18.7 vs. 2.1 ng/ml, respectively). At longer times, however, plasma curcumin concentration equaled between free and encapsulated drug, which was reflected in similar in vivo antimalarial activities in Plasmodium yoelii yoelii-infected mice. Microscopic analysis in blood samples of fluorescently labeled PBMA-MESBMA revealed the presence of the polymer inside P. yoelii yoelii-parasitized erythrocytes one hour after oral administration to infected animals.
KW - Curcumin
KW - Drug delivery
KW - Malaria
KW - PBMA-MESBMA
KW - Plasmodium
KW - Zwitterionic block copolymers
UR - http://www.scopus.com/inward/record.url?scp=85100014585&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000626476700028&DestLinkType=FullRecord&DestApp=WOS_CPL
UR - http://hdl.handle.net/20.500.14342/3593
U2 - 10.1016/j.jconrel.2021.01.028
DO - 10.1016/j.jconrel.2021.01.028
M3 - Article
C2 - 33497747
AN - SCOPUS:85100014585
SN - 0168-3659
VL - 331
SP - 364
EP - 375
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -