Soft- and hard-lipid nanoparticles: a novel approach to lymphatic drug delivery

Arch Pharm Res. 2018 Aug;41(8):797-814. doi: 10.1007/s12272-018-1060-0. Epub 2018 Aug 3.


With the current advance in nanotechnology, the development has accelerated of a number of nanoparticle-type drugs such as nano-emulsions, lipid emulsions, liposomes, and cell therapeutics. With these developments, attempts are being made to apply these new drugs to healing many intractable diseases related to antibody production, autoimmune disorders, cancer, and organ transplantation in both clinical and nonclinical trials. Drug delivery to the lymphatic system is indispensable for treating these diseases, but the core technologies related to the in vivo distribution characteristics and lymphatic delivery evaluation of these particle-type drugs have not yet been established. Additionally, the core technologies for setting up the pharmacotherapeutic aspects such as their usage and dosages in the development of new drugs do not meet the needs of the market. Therefore, it is necessary to consider dividing these particle-type drugs into soft-lipid nanoparticles that can change size in the process of body distribution and hard-lipid nanoparticles whose surfaces are hardened and whose sizes do not easily change in vivo; these soft- and hard-lipid nanoparticles likely possess different biodistribution characteristics including delivery to the lymphatic system. In this review, we summarize the different types, advantages, limitations, possible remedies, and body distribution characteristics of soft- and hard-lipid nanoparticles based on their administration routes. We also emphasize that it will be necessary to fully understand the differences in distribution between these soft- and hard-lipid nanoparticle-type drugs and to establish pharmacokinetic models for their more ideal lymphatic delivery.

Keywords: Biodistribution; Hard-lipid nanoparticles; Lymphatic delivery; Nanoparticle-type drugs; Soft-lipid nanoparticles.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Humans
  • Lipids / chemistry*
  • Lymphatic System / metabolism*
  • Nanoparticles / chemistry*
  • Pharmaceutical Preparations / administration & dosage*


  • Lipids
  • Pharmaceutical Preparations