title: Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers.
abstract: The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.
authors.affiliation: 1] Hunter College-CUNY, Belfer Research Building, 413 E, 69th Street, New York, NY-10021 (USA) [2] The American Museum of Natural History, Central Park West 79th Street, New York, NY-10024 (USA).
authors.forename: Prachi
authors.initials: P
authors.lastname: Anand
authors.affiliation: Indiana University, 800 E. Kirkwood Ave., Bloomington, IN-47405 (USA).
authors.forename: Alison
authors.initials: A
authors.lastname: O'Neil
authors.affiliation: Hunter College-CUNY, Belfer Research Building, 413 E, 69th Street, New York, NY-10021 (USA).
authors.forename: Emily
authors.initials: E
authors.lastname: Lin
authors.affiliation: Indiana University, 800 E. Kirkwood Ave., Bloomington, IN-47405 (USA).
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
authors.affiliation: 1] Hunter College-CUNY, Belfer Research Building, 413 E, 69th Street, New York, NY-10021 (USA) [2] The American Museum of Natural History, Central Park West 79th Street, New York, NY-10024 (USA).
authors.forename: Mandë
authors.initials: M
authors.lastname: Holford
mesh_terms: D000595:Amino Acid Sequence; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D017100:Bacteriophage P22 / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002213:Capsid / Q000737:chemistry; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008969:Molecular Sequence Data; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D020960:omega-Conotoxins / Q000008:administration & dosage* / Q000737:chemistry; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry; D000099193:rab11 GTP-Binding Proteins
chemical_list: D018712:Analgesics, Non-Narcotic; D020960:omega-Conotoxins; D020691:rab GTP-Binding Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099193:rab11 GTP-Binding Proteins; C078452:ziconotide