Peptide-loaded solid lipid nanoparticles (SLN): Influence of production parameters

• Published in: International journal of pharmaceutics Vol. 149; no. 2; pp. 255 - 265
• Main Authors: Almeida, António J., Runge, Stephan, Müller, Rainer H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.04.1997; Elsevier
• Subjects: Biological and medical sciences; General pharmacology; Lysozyme; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein antigens; Solid lipid nanoparticles; Vaccines; Vaccines; Solid lipid nanoparticles; Lysozyme; Protein antigens; Encapsulation; Stability; Pharmaceutical technology; Peptides; Enzyme; Control release polymer; Ester polymer; Solubility; Lipids; Drug carrier; Vaccine; Antigen; Enzymatic activity; Glycosidases; Dosage form; Hydrolases; O-Glycosidases; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(97)04885-0

Solid lipid nanoparticles (SLN) are an alternative to particulate carriers made of biodegradable polyesters. The SLN have been sought as vehicles for drug molecules, and their production often uses physiological lipids or lipid molecules with an history of safe use in human medicine. However, little has been studied regarding the incorporation of peptides into SLN. This report describes the first studies on the incorporation of lysozyme, as a model peptide, in SLN. Previous to nanoparticle preparation, lysozyme was solubilised, until saturation, into the melted lipid phase. Production was carried out by a cold homogenisation process. The entrapment efficiency was dependent on the initial solubility of the peptide in the lipid phase of the final preparation. The influence of formulation parameters (e.g. type of lipid, time of exposure to different temperatures, pressure and the number of homogenisation cycles) on the integrity and activity of the enzyme, was also assessed. The lysozyme molecule remained intact throughout the process without loosing its activity, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and the rate of lysis of Micrococcus lysolideikticus, respectively. This study shows that some proteins are able to endure the harsh procedures of formulation by high pressure homogenisation, making possible the use of SLN as antigen carriers for vaccine delivery.