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.
Highlights
Advances in medicinal chemistry and biotechnology have resulted in the emergence of numerous therapeutic peptides representing one of the fastest-growing class of new active pharmaceutical ingredients
The highest protective effect of PEG-ether nanostructured lipid carriers (NLCs) in comparison to others can be explained by the lack of ester substructures on surfaces susceptible to lipid digesting enzymes of pancreatin
As enzymes cannot enter into the lipid phase, the incorporated peptide is protected from proteolytic cleavage
Summary
Advances in medicinal chemistry and biotechnology have resulted in the emergence of numerous therapeutic peptides representing one of the fastest-growing class of new active pharmaceutical ingredients. The development of advanced drug delivery systems enabling administration via alternative routes and, in particular, the oral route is highly on demand [1]. Among such advanced drug delivery systems, lipid-based nanocarriers have shown considerable potential as they help to overcome the two most important barriers for oral peptide delivery: (i) the enzymatic barrier and (ii) the absorption barrier of the gastrointestinal tract (GIT) [2]. Since the first oral lipid-based nanocarrier formulation for the highly lipophilic peptide cyclosporine entered the global market in the
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