Peptide-mediated drug delivery across the blood-brain barrier for targeting brain tumors

ABSTRACT

Introduction: Transportation of the nutrients and other substances from the blood to the brain is selectively controlled by the brain capillary endothelial cells that form a restrictive barrier, so-called blood-brain barrier (BBB). Currently, there is no unimpeachable approach to overcome the BBB obstructiveness because the existing options are either invasive or ineffective.

Areas covered: This review delineates the biological impacts of BBB on brain drug delivery and targeting. The nanoscaled multifunctional shuttles armed with the targeting entities (e.g., antibodies and peptides) are discussed. Important insights are remarked into the combinatorial screening methodologies used for the identification of de novo peptides capable of crossing BBB and targeting the brain.

Expert opinion: Depending on the physicochemical properties of small molecules and macromolecules, they may cross the BBB and get into the brain either through passive diffusion or active/facilitated transportation and transcytosis in a very selectively controlled manner. Phage-derived shuttle peptides can specifically be selected against BBB endocytic machinery and used in engineering novel peptide-drug conjugates (PDCs). Nanoscaled multitargeting delivery systems encompassing PDCs can overcome the BBB obstructiveness and deliver drugs specifically to diseased cells in the brain with trivial side effects.

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KEYWORDS:

• Blood-brain barrier
• brain drug delivery
• brain drug targeting
• peptide-drug conjugates
• phage display
• shuttle peptides

Article highlights

• The blood-brain barrier (BBB) can selectively control the transportation of nutrients and other substances to the brain.

• Crossing BBB and safe transportation of drugs into the brain is a challenging issue.

• Miniaturized shuttle peptides have been developed to overcome the BBB selective restrictiveness.

• Peptide-drug conjugates have been produced by the conjugation of drugs with BBB-targeting/-crossing antibodies/peptides.

• For efficient brain drug delivery and targeting nanoscaled multi-targeting delivery systems can be used.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to acknowledge Research Center for Pharmaceutical Nanotechnology (RCPN) at Tabriz University of Medical Sciences and thank the scientific staff of the RCPN.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.