Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers

Authors

Prachi Anand, CUNY Hunter College
Alison O’Neil, Indiana University
Emily Lin, CUNY Hunter College
Trevor Douglas, Indiana University
Mandë Holford, CUNY Hunter CollegeFollow

Document Type

Article

Publication Date

August 2015

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.

Comments

This work was originally published in Scientific Reports, available at doi:10.1038/srep12497.