{"entity": "journal", "iuid": "40be762b27164f799800545c43cebcd4", "timestamp": "2026-08-22T06:51:02.435Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Fluids%20Barriers%20CNS.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Fluids%20Barriers%20CNS"}}, "title": "Fluids Barriers CNS", "issn": "2045-8118", "issn-l": null, "publications_count": 1, "publications": [{"entity": "publication", "iuid": "a7316866802c418aaf7b2bc6b1d00a17", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a7316866802c418aaf7b2bc6b1d00a17.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a7316866802c418aaf7b2bc6b1d00a17"}}, "title": "Dual effect of TAT functionalized DHAH lipid nanoparticles with neurotrophic factors in human BBB and microglia cultures.", "authors": [{"family": "Hernando", "given": "Sara", "initials": "S"}, {"family": "Nikolakopoulou", "given": "Polyxeni", "initials": "P"}, {"family": "Voulgaris", "given": "Dimitrios", "initials": "D"}, {"family": "Hernandez", "given": "Rosa Maria", "initials": "RM"}, {"family": "Igartua", "given": "Manoli", "initials": "M"}, {"family": "Herland", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2022-03-17", "journal": {"title": "Fluids Barriers CNS", "issn": "2045-8118", "volume": "19", "issue": "1", "pages": "22", "issn-l": null}, "abstract": "Neurodegenerative diseases (NDs) are an accelerating global health problem. Nevertheless, the stronghold of the brain- the blood-brain barrier (BBB) prevents drug penetrance and dwindles effective treatments. Therefore, it is crucial to identify Trojan horse-like drug carriers that can effectively cross the blood-brain barrier and reach the brain tissue. We have previously developed polyunsaturated fatty acids (PUFA)-based nanostructured lipid carriers (NLC), namely DHAH-NLC. These carriers are modulated with BBB-permeating compounds such as chitosan (CS) and trans-activating transcriptional activator (TAT) from HIV-1 that can entrap neurotrophic factors (NTF) serving as nanocarriers for NDs treatment. Moreover, microglia are suggested as a key causative factor of the undergoing neuroinflammation of NDs. In this work, we used in vitro models to investigate whether DHAH-NLCs can enter the brain via the BBB and investigate the therapeutic effect of NTF-containing DHAH-NLC and DHAH-NLC itself on lipopolysaccharide-challenged microglia.\n\nWe employed human induced pluripotent stem cell-derived brain microvascular endothelial cells (BMECs) to capitalize on the in vivo-like TEER of this BBB model and quantitatively assessed the permeability of DHAH-NLCs. We also used the HMC3 microglia cell line to assess the therapeutic effect of NTF-containing DHAH-NLC upon LPS challenge.\n\nTAT-functionalized DHAH-NLCs successfully crossed the in vitro BBB model, which exhibited high transendothelial electrical resistance (TEER) values (\u22483000 \u03a9*cm2). Specifically, the TAT-functionalized DHAH-NLCs showed a permeability of up to 0.4% of the dose. Furthermore, using human microglia (HMC3), we demonstrate that DHAH-NLCs successfully counteracted the inflammatory response in our cultures after LPS challenge. Moreover, the encapsulation of glial cell-derived neurotrophic factor (GNDF)-containing DHAH-NLCs (DHAH-NLC-GNDF) activated the Nrf2/HO-1 pathway, suggesting the triggering of the endogenous anti-oxidative system present in microglia.\n\nOverall, this work shows that the TAT-functionalized DHAH-NLCs can cross the BBB, modulate immune responses, and serve as cargo carriers for growth factors; thus, constituting an attractive and promising novel drug delivery approach for the transport of therapeutics through the BBB into the brain.", "doi": "10.1186/s12987-022-00315-1", "pmid": "35300705", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8928663"}, {"db": "pii", "key": "10.1186/s12987-022-00315-1"}], "notes": [], "created": "2026-08-20T12:21:08.512Z", "modified": "2026-08-20T12:21:08.568Z"}], "created": "2026-08-20T12:21:08.535Z", "modified": "2026-08-20T12:21:08.535Z"}