000168458 001__ 168458
000168458 005__ 20260205155159.0
000168458 0247_ $$2doi$$a10.1016/j.biomaterials.2025.123867
000168458 0248_ $$2sideral$$a147912
000168458 037__ $$aART-2025-147912
000168458 041__ $$aeng
000168458 100__ $$aConejos-Sánchez, Inmaculada
000168458 245__ $$aA rationally designed polypeptide-based hybrid platform for targeted intranasal brain drug delivery
000168458 260__ $$c2025
000168458 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168458 5203_ $$aIntranasal administration represents a safe and non-invasive route for drug delivery to the brain; however, clinical translation remains limited due to anatomical and physiological barriers. We present a modular hybrid biomaterial platform (NanoInBrain) that bypasses the blood-brain barrier via the olfactory route and enables central nervous system (CNS) drug delivery. The platform integrates a rationally designed polypeptide-based nanocarrier with a depot-forming hydrogel vehicle - a hyaluronic acid–poly-L-glutamate crosspolymer (HA-CP, Yalic®) - adapted from dermatological applications to enhance nasal mucosal retention and brain uptake. We engineered the nanocarrier system using star-shaped poly-L-glutamate (StPGA) architectures and systematically tuned physicochemical properties to optimize mucosal interaction and CNS diffusion. We introduced mucoadhesive and mucodiffusive functionalities via C-terminal odorranalectin (OL) conjugation, which improved nasal epithelium permeation through receptor-mediated mechanisms. Redox-responsive disulfide crosslinking (StPGA-CL-SS) further enhanced mucosal transport by enabling thiol-mediated anchoring to mucin glycoproteins, outperforming inert click-crosslinked variants. Ex vivo Franz diffusion studies and a nasal-mucosa-on-chip model demonstrated robust permeation, with in vivo imaging confirming brain distribution and intracellular uptake in neurons and microglia. Incorporation of HA-CP prolonged nasal residence (∼4 h) and increased total brain accumulation while being well-tolerated. This new platform combines architectural tunability, bioresponsive surface chemistry, and depot-mediated delivery in a scalable, biocompatible nose-to-brain delivery system with potential for treating neurological disorders.
000168458 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-127847OB-I00$$9info:eu-repo/grantAgreement/ES/MICIU/CEX2023-001286-S
000168458 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000168458 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168458 700__ $$aMelnyk, Tetiana
000168458 700__ $$aMasiá, Esther
000168458 700__ $$aMorelló-Bolumar, Daniel
000168458 700__ $$aTortajada-Comeche, Luz
000168458 700__ $$aDolz-Pérez, Irene
000168458 700__ $$aTorrijos-Saiz, Lucía Inés
000168458 700__ $$aTenhaeff, Paula
000168458 700__ $$aRoosz, Julia
000168458 700__ $$aMoruzzi, Alessia
000168458 700__ $$aSogorb, Gloria
000168458 700__ $$aMedel, Maria
000168458 700__ $$aLoskill, Peter
000168458 700__ $$aRoselló, Esther
000168458 700__ $$0(orcid)0000-0002-6873-5244$$aSebastian, Victor$$uUniversidad de Zaragoza
000168458 700__ $$aFlorindo, Helena
000168458 700__ $$aFelip-León, Carles
000168458 700__ $$aNebot, Vicent J.
000168458 700__ $$aHerranz-Pérez, Vicente
000168458 700__ $$aGarcía-Vedugo, José Manuel
000168458 700__ $$aVicent, María J.
000168458 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000168458 773__ $$g328 (2025), 123867 [19 pp.]$$pBiomaterials$$tBiomaterials$$x0142-9612
000168458 8564_ $$s9546786$$uhttps://zaguan.unizar.es/record/168458/files/texto_completo.pdf$$yVersión publicada
000168458 8564_ $$s2524963$$uhttps://zaguan.unizar.es/record/168458/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168458 909CO $$ooai:zaguan.unizar.es:168458$$particulos$$pdriver
000168458 951__ $$a2026-02-05-14:36:59
000168458 980__ $$aARTICLE