Abstract

Background: Oral delivery of biopharmaceuticals is limited by the absorption barriers in the Gastrointestinal Tract (GIT) such as low permeability across the biological membranes and the enzymatic degradation by proteases. In this study, lipid-based drug delivery systems were proposed to overcome these obstacles.

Objective: The aim of this study was to evaluate the effect of particle preparation methods and excipients on the characteristics of Solid Lipid Microparticles (SLM) and Solid Lipid Nanoparticles (SLN).

Method: Different triglycerides (TG) were used as the major excipients for the SLM and SLN. Insulin was used as the model protein; insulin-phospholipid (PL) was prepared to increase drug lipophilicity and compatibility with lipid excipients. Four methods were used for preparing lipid particles, i.e. a Hot Melting Dispersion (HMD) technique, a Solvent Evaporation (SE) method, a modified Solvent Evaporation (mSE) method and a Spray Drying technique. The lipid particles were evaluated in terms of size, size distribution, surface morphology and drug Entrapment Efficiency (EE).

Results: The results suggested that SE method was the most suitable method for preparing insulin-PL loaded Solid Lipid Particles (SLP). No differences were observed when the SLP with a Long Chain Triglyceride (LCT) either a Medium Chain Triglyceride (MCT) in term of size. 70-90% of the lipidified insulin was incorporated in the lipid particles.

Conclusion: The preparation methods affected the size and morphology of SLP significantly, and the selection of lipid excipient should be done based on specific application requirements. Furthermore, the use of the lipidified protein was an efficient way to encapsulate protein in lipid carriers.

Keywords: Excipients, lipidified protein, oral drug delivery, particulate delivery systems, peptide/protein drugs, solid lipid microparticles, solid lipid nanoparticles.

Graphical Abstract