Aptamer-modified M cell targeting liposomes for oral delivery of macromolecules

There is an urgent demand for non-invasive and high compliance delivery systems of macromolecules for long-term therapy. However, oral administration of macromolecules is hindered by low permeability and instability in the gastrointestinal (GI) tract. Therefore, we developed a novel aptamer-modified liposomes (Apt-Lip) with M cell targeting for oral delivery of exenatide (EXT). Firstly, we optimized aptamers to M cells by Cell-SELEX and aptamer truncations. The selected aptamer T-M3 (Apt-T-M3) with high binding affinity (K_d = 176 ± 108 nM) and specificity was modified on the surface of liposomes for targeting M cells. Liposomes were formulated by microfluidics system and characterized in terms of morphology, hydrodynamic diameter, zeta potential, and the efficiency of encapsulation. In comparison with non-targeting liposomes, cell uptake in M cells was significantly enhanced by Apt-Lip. Similarly, the transport efficiency of EXT was 2-fold increase using Apt-Lip in M cells. Additionally, the transepithelial electrical resistance (TEER) of M cell monolayers is significantly reduced. In ex vivo intestinal absorption study, Apt-Lip was proved to possess significantly high intestinal absorption in Peyer's patches (PPs) and M cells-specific targeting capacity. Consequently, Apt-Lip promoted the EXT transport could base not only on M cell mediated transport, but also on enhancement of paracellular permeability. In conclusion, the present study supported Apt-Lip as a promising M cell targeted delivery system for oral delivery of macromolecules.