Solid lipid Particles as Drug Carriers – Effects of Particle Preparation Methods and Lipid Excipients on Particle Characteristics

摘要

Background: Oral delivery of biopharmaceuticals is limited by the absorption barriers inthe Gastrointestinal Tract (GIT) such as low permeability across the biological membranes and the enzymaticdegradation by proteases. In this study, lipid-based drug delivery systems were proposed toovercome these obstacles.Objective: The aim of this study was to evaluate the effect of particle preparation methods and excipientson 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. Insulinwas used as the model protein; insulin-phospholipid (PL) was prepared to increase drug lipophilicityand compatibility with lipid excipients. Four methods were used for preparing lipid particles, i.e. a HotMelting 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 ofsize, size distribution, surface morphology and drug Entrapment Efficiency (EE).Results: The results suggested that SE method was the most suitable method for preparing insulin-PLloaded Solid Lipid Particles (SLP). No differences were observed when the SLP with a Long ChainTriglyceride (LCT) either a Medium Chain Triglyceride (MCT) in term of size. 70-90% of the lipidifiedinsulin was incorporated in the lipid particles.Conclusion: The preparation methods affected the size and morphology of SLP significantly, and theselection 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.