Solid lipid nanoparticles for hydrophilic drugs

J Control Release. 2021 Jul 10:335:457-464. doi: 10.1016/j.jconrel.2021.05.032. Epub 2021 May 25.


Hydrophilic drugs are proficient therapeutic agents however, delivery of these drugs is a difficult task. Hence, developing an efficient drug delivery system may require a multipronged approach. Colloidal drug delivery systems such as emulsions, liposomes, nanoemulsions, polymeric nanoparticles, and niosomes are known to enhance drug entrapment, bioavailability, and to improve the pharmacokinetic profiles of hydrophilic drugs. However, issues such as drug leakage and burst release are frequently reported with such systems. Solid lipid nanoparticles (SLNs) were developed as an alternative to the traditional colloidal drug carriers to overcome these issues. Although SLNs have been widely studied as carriers for hydrophobic drugs, delivery of hydrophilic molecules remains a challenge. Hence, the current review focuses on different approaches that have been used for the delivery of hydrophilic drugs using SLNs. It not only discusses various modifications in the traditional methods for the synthesis but also emphasizes modifications of the hydrophilic drugs itself that can help in their efficient entrapment into SLNs drug carriers.

Keywords: Coacervation technique; Drug delivery; Hydrophilic drugs; Hydrophobic ion pairing; Lipid polymer conjugate; Lipophilic prodrug; Solid lipid nanoparticles.

Publication types

  • Review

MeSH terms

  • Biological Availability
  • Drug Carriers
  • Drug Delivery Systems
  • Hydrophobic and Hydrophilic Interactions
  • Lipids*
  • Nanoparticles*


  • Drug Carriers
  • Lipids