RT Journal Article
T1 Delivery of monoclonal antibodies to the brain: the impact of nanocarrier structure
A1 Piñeiro Alonso, Laura
A1 Rubio Prego, Inés
A1 López Estévez, Ana María
A1 Garrido Gil, Pablo
A1 Valenzuela Limiñana, Rita
A1 Labandeira García, José Luis
A1 Aguiar Fernández, Pablo
A1 Rodríguez Pérez, Ana Isabel
A1 Alonso Fernández, María José
K1 Monoclonal antibodies
K1 Nanomedicine
K1 Brain delivery
K1 Diffusivity
AB Monoclonal antibodies (mAbs) are promising therapeutic agents for neurological disorders due to their high specificity. However, their clinical application is significantly hindered by their poor transport across the blood-brain barrier (BBB) and their limited diffusion within the brain parenchyma. While significant efforts have been oriented to tackle the first barrier, the challenge of efficient brain diffusion remains largely underexplored. To address this, we have developed and evaluated two structurally distinct nanosystems for mAb delivery to the brain: PEGylated polyglutamic acid nanocapsules (PGA-PEG NCs) and PGAC14-based nanoassemblies (PGAC14 NAs). Both formulations encapsulated efficiently the model mAb bevacizumab (BVZ) while they exhibited different physicochemical properties. Namely, PGA-PEG NCs displayed a size of 80 nm and a neutral zeta potential, whereas PGAC14 NAs featured an ultra-small size of 40 nm and a negative surface charge. After assessing their diffusion capacity using immunofluorescence, we concluded that PGAC14 NAs exhibited the highest brain diffusion together with a favorable neuroinflammatory profile. This was likely driven by their small size and negative charge, along with a selective ability to interact with and deliver BVZ intracellularly to neuronal cells upon intraparenchymal administration. These findings provide key insights into optimizing nanocarrier design for improved mAb delivery to the brain
PB Springer Nature
SN 2190-393X
YR 2025
FD 2025
LK https://hdl.handle.net/10347/43045
UL https://hdl.handle.net/10347/43045
LA eng
NO Pineiro-Alonso, L., Rubio-Prego, I., López-Estévez, A.M. et al. Delivery of monoclonal antibodies to the brain: the impact of nanocarrier structure. Drug Deliv. and Transl. Res. (2025). https://doi.org/10.1007/s13346-025-01957-y
NO This work was supported by the government of Xunta de Galicia (Competitive Reference Groups, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, Ref: ED431C 2021/17; ED431C 2022/41); and by the FEDER/Spanish Ministry of Science, Innovation and Universities (AEI/Project PID2020-119368RB-I00; PID2021-126848NB-I00); and (AEI/Project PID2023-150743OB-I00). Laura Piñeiro Alonso acknowledges a grant (ED481A 2021/098) from Xunta de Galicia “Axudas de apoio á etapa predoutoral 2021”. Inés Rubio-Prego acknowledges a grant (IFI23/00035) from Instituto de Salud Carlos III “Contratos i-PFIS: Doctorados ISS-empresa en Ciencias y Tecnologías de la Salud”.
DS Minerva
RD 23 may 2026