Professor University of Copenhagen Copenhagen OE, Hovedstaden, Denmark
Upon oral administration, peptides are labile to acid and enzymatic hydrolysis and has poor permeability across the intestinal wall due to their large size and hydrophilicity. Self nano-emulsifying drug delivery system (SNEDDS) possess properties which could enable overcoming these barriers. SNEDDS are isotropic mixtures of oil, surfactant and co-surfactant, which upon dispersion in aqueous media form a nano-sized oil-in-water emulsion. SNEDDS possess advantages such as gentle preparation and innate permeation enhancement. Increasing the lipophilicity of peptides by complexing with phospholipids (PL; Peptide:PL) improve the loading of peptides into SNEDDS. Peptides were complexed with different types of PL namely, dimyristoyl phophatidylglycerol (DMPG), monoacyl phosphatidylcholine (MAPC) and dioleoyltrimethylammonium propane (DOTAP) using freeze-drying and loaded into SNEDDS based on medium chain (C8-C10) glycerides. SNEDDS are characterised with regard to e.g. formed droplet size, propensity be digested, ability to protect peptides from proteolysi and permeation in Caco-2 cells. SNEDDS with different in vitro properties were dosed by oral gavage to rats and the pharmacokinetic profiles was determined. By this approach it was possible to develop the SNEDDS containing peptide:PL complexes with a relatively high (5%) and reproducible bioavailability.
Learning Objectives:
Upon completion the participant will be able to design SNEDDS using Design of Experiment.
Upon completion, participant will be able to complex peptides with lipophilic surfactants
Upon completion, participant will be able to describe which in vitro models that can best predict the absorption of peptides.