Solid lipid nanocarriers diffuse effectively through mucus and enter intestinal cells - but where is my peptide?

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Biotechnology

Background:

• Peptides are valuable therapeutics but face challenges in oral absorption due to the intestinal barrier.
• Developing strategies to enhance peptide permeation across the intestinal epithelium is crucial for effective drug delivery.

Purpose of the Study:

• To evaluate the efficacy of Hydrophobic Ion Pairing (HIP) combined with Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for improving peptide intestinal transport.
• To assess peptide encapsulation and cellular uptake using Caco-2 and Caco-2/HT29-MTX cell models.

Main Methods:

• Formation of a Hydrophobic Ion Pair (HIP) between Leuprolide (LEU) and sodium docusate.
• Encapsulation of the HIP-peptide within SLN and NLC.
• Evaluation of particle uptake and transport across Caco-2 and Caco-2/HT29-MTX cell monolayers using confocal microscopy and flow cytometry.

Main Results:

• High encapsulation efficiencies were achieved for LEU-HIP in both NLC (84%) and SLN (85%).
• Nanoparticles were successfully internalized by Caco-2 cells (82% SLN, 99% NLC) and demonstrated mucus penetration.
• Despite high cellular uptake, LEU transport across the cell monolayers was not improved due to burst release from the nanoparticles.

Conclusions:

• While HIP and lipid nanoparticles facilitate peptide encapsulation and cellular uptake, their current combination does not enhance intestinal peptide transport.
• Peptide burst release, influenced by particle shape and HIP stability, is a key limitation.
• Further research should focus on improving peptide lipidization to ensure sustained release and leverage nanocarrier-mediated transport for enhanced oral peptide delivery.