Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration
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 po...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/8/1312 |
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| author | Iram Shahzadi Andrea Fürst Patrick Knoll Andreas Bernkop-Schnürch |
| author_facet | Iram Shahzadi Andrea Fürst Patrick Knoll Andreas Bernkop-Schnürch |
| author_sort | Iram Shahzadi |
| collection | DOAJ |
| description | 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<sub>octanol/water</sub> 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% (<i>w</i>/<i>v</i>). 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. |
| first_indexed | 2024-03-10T08:28:08Z |
| format | Article |
| id | doaj.art-35fd015410b14fb6b90bcd90d0e3ad23 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T08:28:08Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-35fd015410b14fb6b90bcd90d0e3ad232023-11-22T09:15:56ZengMDPI AGPharmaceutics1999-49232021-08-01138131210.3390/pharmaceutics13081312Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface DecorationIram Shahzadi0Andrea Fürst1Patrick Knoll2Andreas Bernkop-Schnürch3Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaThis 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<sub>octanol/water</sub> 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% (<i>w</i>/<i>v</i>). 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.https://www.mdpi.com/1999-4923/13/8/1312insulinnanostructured lipid carrierspepsinpancreatinproteolysis |
| spellingShingle | Iram Shahzadi Andrea Fürst Patrick Knoll Andreas Bernkop-Schnürch Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration Pharmaceutics insulin nanostructured lipid carriers pepsin pancreatin proteolysis |
| title | Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration |
| title_full | Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration |
| title_fullStr | Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration |
| title_full_unstemmed | Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration |
| title_short | Nanostructured Lipid Carriers (NLCs) for Oral Peptide Drug Delivery: About the Impact of Surface Decoration |
| title_sort | nanostructured lipid carriers nlcs for oral peptide drug delivery about the impact of surface decoration |
| topic | insulin nanostructured lipid carriers pepsin pancreatin proteolysis |
| url | https://www.mdpi.com/1999-4923/13/8/1312 |
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