Surface-modified liposomes with polyvinyl alcohol derivatives improve mucus penetration and oral absorption: A potential alternative to polyethylene glycol

Polyethylene glycol-modified (PEG-modified) nanocarriers are widely used as mucus-penetrating systems for oral administration. In this study, we developed a low-molecular-weight polyvinyl alcohol (PVA) bearing alkyl groups at molecular ends as a potential alternative to PEG for imparting mucus permeability to nanocarriers. We also evaluated its effects on mucus permeability and its applicability to oral drug delivery. The particle sizes of PVA-modified liposomes (PVA-Lip) and PEG-modified liposomes (PEG-Lip) were approximately 150 nm and 130 nm, respectively, and both exhibited monodisperse size distributions. PVA-Lip showed greater apparent mucus permeability than PEG-Lip. Furthermore, when liposomes encapsulating fluorescein isothiocyanate-dextran with an average molecular weight of 3,000-5,000 (FD4) as a peptide model were orally administered to rats, PVA-Lip and PEG-Lip exhibited similar overall FD4 absorption, with insignificant differences in the area under the plasma concentration-time curve (AUC). In repeated oral administration studies, the AUC of PEG-Lip decreased by approximately 43 % compared with the initial dose, whereas that of PVA-Lip decreased minimally. This decreased AUC may be associated with antibody responses, and PVA-Lip may be less susceptible to antibody-related effects than PEG-Lip. Collectively, these findings suggest that alkyl-terminated PVA could be an alternative to PEG for oral delivery.