Enhancing the pharmacokinetic/pharmacodynamic properties of therapeutic nucleotides using lipid nanoparticle systems

Future Med Chem. 2015;7(13):1751-69. doi: 10.4155/fmc.15.108. Epub 2015 Sep 24.

Abstract

Although activity has been reported in vivo, free nucleic acid-based drugs are rapidly degraded and cleared following systemic administration. To address these challenges and improve the potency and bioavailability of genetic drugs, significant efforts have been made to develop effective delivery systems of which lipid nanoparticles (LNP) represent the most advanced technology currently available. In this review, we will describe and discuss the improvements to the pharmacokinetic and pharmacodynamic properties of nucleic acid-based drugs mediated by LNP delivery. It is envisioned that the significant improvements in potency and safety, largely driven by the development of LNP encapsulated siRNA drugs, will be translatable to other types of genetic drugs and enable the rapid development of potent molecular tools and drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA, Catalytic / administration & dosage
  • DNA, Catalytic / pharmacokinetics
  • DNA, Catalytic / pharmacology
  • Drug Carriers / chemistry*
  • Drug Compounding / methods
  • Drug Delivery Systems
  • Humans
  • Lipids / chemistry*
  • MicroRNAs / administration & dosage
  • MicroRNAs / pharmacokinetics
  • MicroRNAs / pharmacology
  • Nanoparticles / chemistry*
  • Nucleotides / administration & dosage*
  • Nucleotides / pharmacokinetics*
  • Nucleotides / pharmacology
  • RNA, Catalytic / administration & dosage
  • RNA, Catalytic / pharmacokinetics
  • RNA, Catalytic / pharmacology
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / pharmacokinetics
  • RNA, Small Interfering / pharmacology

Substances

  • DNA, Catalytic
  • Drug Carriers
  • Lipids
  • MicroRNAs
  • Nucleotides
  • RNA, Catalytic
  • RNA, Small Interfering