Development of lipid nanoparticles for nisin delivery by oral route
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Date
2023-07-11
Authors
Sodimanage, Chathuri Isurika
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Abstract
The current challenge of administering therapeutic peptides through invasive routes can be overcome by developing oral peptide formulations. However, delivering peptides orally poses significant difficulties due to the harsh conditions of the gastrointestinal (GI) tract. A promising solution to address this problem is utilizing lipid nanocarriers. These nanocarriers offer versatile approaches by using different lipid building blocks to create diverse lipid nanocarriers capable of overcoming the enzymatic barrier, mucus barrier, and epithelial barrier of the GI tract. In this study, lipid nanoparticles with a composition similar to liposomes were formulated using an innovative solvent-free process. Nisin, an antibacterial peptide, was employed as the peptide model. The process was further refined to achieve 99% recovery of the drug at the completion of the procedure. During the initial optimization steps, the Micro BCA assay was utilized to quantify Nisin. However, for the testing of nisin-loaded formulations, LC-MS was employed instead. The successful separation of nanoparticles from free nisin was accomplished using the tangential flow filtration (TFF) technique. Approximately 94% of the nanoparticles were recovered in the retentate, while 80% of the free drug passed into the filtrate. Finally, nisin-encapsulated formulations were prepared and subjected to purification using the optimized techniques. To screen the impact of three specific process parameters on encapsulation efficiency, a Design of Experiments approach was employed.
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Keywords
Lipid nanoparticles, Nisin, Tangential flow filtration, Micro BCA