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

Abstract

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 Poctanol/water 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% (w/v). 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.

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer

“…It was found that increasing the degree of glycerol esterification resulted in a significant increase in ZP value. This is attributed to the negative charge produced by the free carboxylic group in the free FA [ 26 ]. The present results are in agreement with various studies that showed that NLC prepared from LCFA has a ZP value less than LCM and LCT [ 27 , 28 ].…”

Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

“…The addition of spatially incompatible liquid lipid(s) to the formulations is beneficial in two aspects, it leads to the formation of a less-ordered crystalline structure ( Figure 2 ), ensuring extra area for drug loading, decreases the crystalline degree of the lipid matrix and averts drug expulsion [ 128 , 167 ]. Usually, the liquid lipid is included up to 30% of the total lipid amount in the NLCs formulations [ 168 , 169 ]. As such, researchers often use castor/olive/argan oil, oleic acid, Miglyol ® 812 (medium-chain triglycerides), propylene glycol dicaprylocaprate—Labrafac™ PG (Gattefosse, Saint-Priest, France), or caprylocaproyl macrogol-8 glycerides—Labrasol ® (Gattefosse, Saint-Priest, France) [ 170 , 171 , 172 ].…”

Bilosomes as Nanocarriers for the Drug and Vaccine Delivery against Gastrointestinal Infections: Opportunities and Challenges

“…Chitosan also opens intercellular spaces of enterocytes and facilitates drug penetration. The P-glycoprotein (Pgp) inhibition reduced the drug efflux, while enhancing their adsorption and penetration [ 59 , 60 ]. Phospholipid-containing liposomes (liquid) are disrupted upon exposure to 10 mM bile salts, losing the entire payload [ 61 ].…”