Lipid-based nanosuspensions for oral delivery of peptides, a critical review

Int J Pharm. 2018 Apr 25;541(1-2):117-135. doi: 10.1016/j.ijpharm.2018.02.038. Epub 2018 Feb 21.

Abstract

Peptides are therapeutic molecules that can treat selectively and efficiently a wide range of pathologies. However, their intrinsic properties cause their rapid degradation in the human gastrointestinal (GI) tract resulting in poor bioavailability after oral administration. Yet, their encapsulation in nanocarriers offers them protection from this harsh environment and increases their permeability across the epithelium border. In particular, Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) have proven to improve peptide oral bioavailability. This article details different techniques used to produce SLN and NLC with potential or effective peptide encapsulation. Basic principles of covalent and non-covalent lipidization are described and discussed as a prerequisite to improve hydrophilic peptide encapsulation in lipid-based nanosuspensions. The last part of this review provides the key evaluation techniques to assay SLN and NLC for peptide oral bioavailability enhancement. Methods to assess the protective effects of the carriers are described as well as the techniques to evaluate peptide release upon lipid digestion by lipases. Furthermore, this review suggests different techniques to measure permeability improvements and describes the main in vitro cell models associated.

Keywords: Lipid; Lipidization; Peptide; Permeation; Process; SLN.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Cell Line
  • Drug Carriers / chemistry*
  • Drug Compounding / instrumentation
  • Drug Compounding / methods
  • Drug Liberation
  • Emulsions
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lipids / chemistry*
  • Nanoparticles / chemistry*
  • Peptides / administration & dosage*
  • Peptides / pharmacokinetics
  • Permeability
  • Suspensions

Substances

  • Drug Carriers
  • Emulsions
  • Lipids
  • Peptides
  • Suspensions