Nanomedicine based strategies for oligonucleotide traversion across the blood-brain barrier

J Control Release. 2023 Feb:354:554-571. doi: 10.1016/j.jconrel.2023.01.031. Epub 2023 Jan 19.

Abstract

Neurological disorders are considered the most prominent cause of disability worldwide. The major hurdle in the management of neurological disorders is the existence of the blood-brain barrier (BBB), which hinders the entry of several therapeutic moieties. In recent years, oligonucleotides have gained tremendous attention for their target specificity, diminished dose and adverse effects, thereby halting disease progression. However, enzymatic degradation, rapid clearance, limited circulation and availability at the bio-active site, etc., limit its clinical translation. Nanomedicine has opened up a breadth of opportunities in the delivery of oligonucleotides across the BBB. This review addresses the pitfalls associated with oligonucleotide delivery in traversing the BBB via nanotherapeutics for the management of brain disorders. Regulatory perspectives pertaining to hastening the clinical translation of oligonucleotide-loaded nanocarriers for brain delivery have been highlighted.

Keywords: Blood–brain barrier; Central nervous system; Nanocarriers; Neurological disorders; Oligonucleotides; Regulatory perspectives.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier / metabolism
  • Drug Delivery Systems
  • Humans
  • Nanomedicine
  • Nanoparticles* / chemistry
  • Nervous System Diseases* / metabolism
  • Oligonucleotides

Substances

  • Oligonucleotides