PLGA nanoparticles for peroral delivery: How important is pancreatic digestion and can we control it?

Eur J Pharm Biopharm. 2016 Nov:108:32-40. doi: 10.1016/j.ejpb.2016.08.009. Epub 2016 Aug 20.

Abstract

Biodegradable nanoparticles made of Poly(lactide-co-glycolide) are increasingly proposed for the improvement of oral drug absorption, but also as carriers for the treatment of colonic diseases. Unfortunately, our knowledge of the digestibility of PLGA-NPs is rather limited. Therefore, we investigated the impact of pancreatin on the digestibility of PLGA-NPs stabilized with different emulsifiers. The pancreatin induced degradation was monitored by the pH-stat method and an enzymatic l-lactic acid assay. A high digestibility was found for poloxamer 188 and polysorbate 80 stabilized PLGA-NPs. The digestion could be blocked by Orlistat, indicating a major role of pancreatic lipase. PLGA-NPs stabilized with Poly(vinyl alcohol) (=PVA) were not digested at comparable surfactant concentrations (0.6%). However, PLGA-NPs stabilized with very low amounts of PVA (0.1%) were digestible. In conclusion, PLGA-NPs are substrates for the pancreatic lipase. The digestibility can be enhanced or blocked by the proper selection of the surfactant composition and concentration.

Keywords: Biodegradable polymers; Lipase; Nanoparticles; Oral delivery; PLGA; Pancreatic lipase; Pancreatin, digestion; Peroral; Poly(lactide-co-glycolide).

MeSH terms

  • Administration, Oral*
  • Animals
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid / chemistry*
  • Lipase / chemistry
  • Nanoparticles / chemistry*
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Pancreatin / chemistry
  • Particle Size
  • Poloxamer / chemistry
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry
  • Polysorbates / chemistry
  • Polyvinyl Alcohol / chemistry
  • Surface-Active Agents / chemistry
  • Swine

Substances

  • Drug Carriers
  • Polymers
  • Polysorbates
  • Surface-Active Agents
  • Poloxamer
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Pancreatin
  • Polyvinyl Alcohol
  • Lipase