Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs III — the Effect of Fed State Conditions on the In Vitro Release and Degradation of Desmopressin

Abstract

The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles consisting of trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18), respectively. Fasted state and fed state media with varying phospholipid and bile salt concentrations, as well as fed state media with milk and oleic acid glycerides, respectively, were used as the release media. The presence of oleic acid glycerides accelerated the release of desmopressin significantly from all solid lipid particles both in the presence and absence of lipase. The presence of oleic acid glycerides also reduced the degradation rate of desmopressin, probably due to the interactions between the lipids and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract.

Solid Lipid Microparticles for Oral Delivery of Catalase: Focus on the Protein Structural Integrity and Gastric Protection

“…The second feature, however, is essential for the emulsification and digestion of the lipid matrix by bile salts and physiological lipases, allowing the release of the drug into the intestinal environment. Glyceryl trimyristate or trimyristin (Dynasan 114) has shown a good balance between those two properties and it is, therefore, suitable for the formulation of protein-loaded SLMs for oral administration. − These studies confirmed that the intestinal release of the encapsulated proteins (β-galactosidase, lysozyme, and desmopressin) depends on a lipase-mediated degradation mechanism, which is related to the lipid composition and to the fed–fasted state conditions. However, there is little data about the ability of SLMs to retain the incorporated protein after exposure to gastric media.…”

Synergistic Catalysis by “Polymeric Microzymes and Inorganic Nanozymes”: The 1+1>2 Effect for Intramolecular Cyclization of Peptides

“…The concentration of DDAVP was determined using HPLC with a diode-array detector (Chen et al, 2016 ). The HPLC method for DDAVP followed a previous work (Christophersen et al, 2014 ).…”