Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration

• Published in: Pharmaceutics Vol. 13; no. 8; p. 1312
• Main Authors: Shahzadi, Iram, Fürst, Andrea, Knoll, Patrick, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-08-2021; MDPI
• Subjects: Cell culture; Drug delivery systems; Efficiency; Enzymes; Glycerol; Insulin; Lipids; nanostructured lipid carriers; pancreatin; pepsin; Peptides; Pharmaceuticals; Phase transitions; proteolysis; Sodium; Surfactants; France; Austria; Germany; insulin; nanostructured lipid carriers; pancreatin; proteolysis; pepsin
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13081312

This study was aimed to evaluate the impact of surfactants used for nanostructured lipid carriers (NLCs) to provide enzymatic protection for incorporated peptides. Insulin as a model peptide was ion paired with sodium dodecyl sulfate to improve its lipophilicity. Three NLC formulations containing polyethylene glycol ester (PEG-ester), polyethylene glycol ether (PEG-ether), and polyglycerol ester (PG-ester) surfactants were prepared by solvent diffusion method. NLCs were characterized regarding particle size, polydispersity index, and zeta potential. Biocompatibility of NLCs was assessed on Caco-2 cells via resazurin assay. In vitro lipolysis study was performed using a standard lipid digestion method. Proteolytic studies were performed in simulated gastric fluid containing pepsin and simulated intestinal fluid containing pancreatin. Lipophilicity of insulin in terms of log P
was improved from -1.8 to 2.1. NLCs were in the size range of 64-217 nm with a polydispersity index of 0.2-0.5 and exhibited a negative surface charge. PG-ester NLCs were non-cytotoxic up to a concentration of 0.5%, PEG-ester NLCs up to a concentration of 0.25% and PEG-ether NLC up to a concentration of 0.125% (
/
). The lipolysis study showed the release of >90%, 70%, and 10% of free fatty acids from PEG-ester, PG-ester, and PEG-ether NLCs, respectively. Proteolysis results revealed the highest protective effect of PEG-ether NLCs followed by PG-ester and PEG-ester NLCs for incorporated insulin complex. Findings suggest that NLCs bearing substructures less susceptible to degrading enzymes on their surface can provide higher protection for incorporated peptides toward gastrointestinal proteases.