Intrinsic targeting of inflammatory cells in the brain by polyamidoamine dendrimers upon subarachnoid administration

• Published in: Nanomedicine (London, England) Vol. 5; no. 9; pp. 1317 - 1329
• Main Authors: Dai, Hui, Navath, Raghavendra S, Balakrishnan, Bindu, Guru, Bharath Raja, Mishra, Manoj K, Romero, Roberto, Kannan, Rangaramanujam M, Kannan, Sujatha
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2010
• Subjects: Alzheimer's disease; Animal models; Animals; Animals, Newborn; Astrocytes; Astrocytes - metabolism; Brain; Brain - metabolism; Cerebral palsy; Cerebral Palsy - metabolism; Chromatography, High Pressure Liquid; Dendrimers; Dendrimers - administration & dosage; Dendrimers - chemistry; Dendrimers - metabolism; Female; Fluorescein-5-isothiocyanate - chemistry; Gene therapy; Health aspects; Inflammation; Male; Microglia; Microglia - metabolism; microglia-targeted drug delivery to the brain; Multiple sclerosis; nanotechnology; Neonates; Neurodegenerative diseases; neuroinflammation; PAMAM dendrimers; Paralysis; polyamidoamines; Rabbits; Subarachnoid Space - metabolism
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm.10.89

Understanding the interactions between nanomaterials and disease processes is crucial for designing effective therapeutic approaches. This article explores the unusual neuroinflammation targeting of dendrimers (with no targeting ligands) in the brain, with significant consequences for nanoscale materials in medicine. The biodistribution of fluorescent-labeled neutral generation-4- polyamidoamine dendrimers (∼4 nm) in a rabbit model of cerebral palsy was explored following subarachnoid administration. These dendrimers, with no targeting ligands, were localizing in activated microglia and astrocytes (cells responsible for neuroinflammation), even in regions far moved from the site of injection, in newborn rabbits with maternal inflammation-induced cerebral palsy. This intrinsic ability of dendrimers to localize inactivated microglia and astrocytes can enable targeted delivery of therapeutics in disorders such as cerebral palsy, Alzheimer s and multiple sclerosis.