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cc-by-nc-nd (c) Elsevier B.V., 2025
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/227593

PEGylated PLGA nanoparticles prepared from nano-emulsion templates as versatile platforms to cross blood-brain barrier models

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PEGylation prevents aggregation and enhances the systemic circulation of nanoparticles (NPs), improving the delivery of actives to targeted cells. In this study, a conjugation reaction was used to attach polyethylene glycol (PEG) chains of molecular weights 750 and 5000 Da onto the surface of poly(lactic-co-glycolic acid) (PLGA) NPs obtained using the phase inversion composition methods, with carbodiimide/N-hydroxysuccinimide (NHS) and carbodiimide/sulfo-NHS activation reactions. Proton nuclear magnetic resonance indicated a higher degree of decoration (ca. 44.7 %) when carbodiimide/sulfo-NHS activation and PEG low molecular weight (750 Da) were used. Short incubation times (2 h at 37 ◦C) in the presence of 10 % fetal bovine serum showed no significant changes in particle size compared to pristine NPs. After 5 h of incubation, PEGylated NPs exhibited increase size (101.4 ± 15.3 nm) and polydispersity (0.6 ± 0.01). The presence of PEG chains decorating NPs reduced antioxidant release from NPs to ca. 10 % after 24 h at 37 ◦C following the Korsmeyer–Peppas model and governed by a Fickian diffusion mechanism. The antioxidant capacity of NPs showed a dose-activity relationship with ca. 60 % inhibition at 0.16 mg mL− 1 NP concentration and an EC50 of 51.7 ± 3.3 μg mL− 1 . Cell culture studies indicated no cytotoxicity for PLGA and PEGylated NPs up to 0.05 mg mL− 1 . Internalization studies confirmed cellular uptake into SHSY5Y cells. The impact of PEGylated NPs on blood-brain barrier (BBB) permeabilization was evaluated in a BBB-on-chip model, showing that PLGA encapsulation and PEGylated NPs, though to a lesser extent, facilitated crossing and permeabilization through the endothelial layer, demonstrating their potential for effective brain delivery.

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LÓPEZ MITJAVILA, Joan Josep, et al. PEGylated PLGA nanoparticles prepared from nano-emulsion templates as versatile platforms to cross blood-brain barrier models. Journal of Drug Delivery Science and Technology. 2025. Vol. 110. ISSN 1773-2247. [consulted: 6 of June of 2026]. Available at: https://hdl.handle.net/2445/227593

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