Self-emulsifying peptide drug delivery systems: How to make them highly mucus permeating

Abstract

AimIt was the aim of this study to evaluate the mucus permeating properties of self-emulsifying drug delivery systems (SEDDS) exhibiting different size and zeta potential. MethodsVarious SEDDS were prepared and characterized regarding droplet size, zeta potential and stability. Desmopressin was incorporated as model peptide drug and log P (SEDDS/water) was determined. Thereafter, mucus permeation studies with freshly isolated porcine mucus via Transwell method were performed. Moreover, the impact of water movement on mucus permeation of SEDDS was investigated. Different types of nanocarriers including nanoparticles and liposomes served as references. ResultsSEDDS exhibited an initial droplet size of 25.0 ± 2.2, 49.5 ± 4.6, 123.5 ± 12.1, 226.2 ± 93.4 and 502.9 ± 93.7 nm and a zeta potential of +24.4 ± 4.6, +10.6 ± 2.0, 0.2 ± 3.8, −8.2 ± 3.4 and −35.1 ± 2.7 mV. Log P was in the range of 1.29–2.09 and mucus permeation studies with these SEDDS revealed a clear correlation between droplet size and permeation rate. The smaller SEDDS were, the higher their mucus permeating properties were. Negatively charged SEDDS demonstrated a higher permeation rate than positively charged SEDDS. In comparison to liposomes and solid nanocarriers SEDDS exhibited up to 5-fold higher mucus permeating properties. ConclusionSmall droplet size and negative zeta potential of SEDDS could be identified as key parameters for their mucus permeating properties.