Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines

Adv Drug Deliv Rev. 2016 Sep 1:104:93-109. doi: 10.1016/j.addr.2015.12.004. Epub 2015 Dec 10.

Abstract

Small interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bioconjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. However, most cases address local applications or diseases in the filtering organs, reflecting remaining challenges in systemic delivery of siRNA. The difficulty in siRNA delivery is in large part due to poor circulation stability and unfavorable pharmacokinetics and biodistribution profiles of siRNA. This review describes the pharmacokinetics and biodistribution of siRNA nanomedicines, focusing on those reported in the past 5years, and their pharmacological effects in selected disease models such as hepatocellular carcinoma, liver infections, and respiratory diseases. The examples discussed here will provide an insight into the current status of the art and unmet needs in siRNA delivery.

Keywords: Biodistribution; Delivery; Pharmacokinetics; RNA interference; Small interfering RNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / therapy*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / therapy*
  • Nanomedicine*
  • RNA Interference
  • RNA, Small Interfering* / pharmacokinetics
  • RNA, Small Interfering* / therapeutic use
  • RNAi Therapeutics*
  • Respiratory Tract Diseases / genetics
  • Respiratory Tract Diseases / metabolism
  • Respiratory Tract Diseases / therapy
  • Tissue Distribution

Substances

  • RNA, Small Interfering