We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD-loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine-bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy. 1. Introduction Liposomes are a very attractive drug delivery system because they are physically and chemically well-characterized structures that can be delivered through almost all routes of administration and are biocompatible [1–3]. We have developed a submicron-sized (100–200？nm) mucoadhesive liposomal system by modifying the liposome surface with a mucoadhesive polymer such as chitosan to achieve an oral peptide formulation [4, 5]. The effectiveness of polymer-modified liposomes was confirmed by the enhanced and prolonged pharmacological effect of peptide drugs such as insulin, which was orally administered in a polymer-coated liposomal form to rats. Therefore, it is important to characterize the mucoadhesive properties of oral liposomal systems in vivo based on liposomal behavior in the body [6]. In a previous study, we examined the mucosal layer of the rat intestine to detect organic dye-labeled liposomes by confocal laser scanning microscopy (CLSM) after administering these particulate systems [4]. In in vivo experiments, near-infrared (NIR) optical imaging is a powerful tool for real-time observation of the dynamic behavior of liposomes because it is a minimally invasive, nonionizing method that permits sensitive deep tissue imaging [7, 8]. However,
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