Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers. Academic Article uri icon

Overview

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.

publication date

  • August 3, 2015

Research

keywords

  • Analgesics, Non-Narcotic
  • Bacteriophage P22
  • Blood-Brain Barrier
  • Drug Delivery Systems
  • Nanocomposites
  • omega-Conotoxins

Identity

PubMed Central ID

  • PMC4522602

Scopus Document Identifier

  • 84938524946

Digital Object Identifier (DOI)

  • 10.1038/srep12497

PubMed ID

  • 26234920

Additional Document Info

volume

  • 5