Formulation and Quality – Chemical
2019 PharmSci 360
While peptide- and protein-based therapeutics have been developed significantly in the past decades, delivery challenges have limited their clinical use. One current strategy to improve oral bioavailability is targeting intestinal transporters, such as PepT1. In this work, a candidate peptide, usually administered subcutaneously for the treatment of type 2 diabetes, was encapsulated into liposomes. To achieve a well-controlled release, it was proposed to employ Layer-by-Layer (LbL) assembly to carefully tune drug release and enhance intestinal drug absorption. It was demonstrated the possibility to formulate <200 nm layered NPs, loaded with peptide and able to target PepT1. Confocal images showed colocalization of NPs with cell membrane and transport experiments pointed out a 9-times transport increase of the peptide when encapsulated in LbL NPs compared to free drug. Bringing together strategies of tissue-specific targeting and Layer-by-Layer assembly, it is possible to develop innovative formulations and identify a candidate with translational potential. Input of the strategy on oral administration of peptide was evaluated in vivo on diabetic mice.