Preparation and Evaluation of Integrin Receptor-Mediated Targeting Drug Liposomes

Abstract

To promote the therapeutic efficiency of drug liposomes, ligand-modified targeting liposomes have received extensive attentions in recent years. RGD peptide (Arginine-Glycine-Aspartic acid), which is a ligand of the integrin receptors, has been widely used to enhance the interaction between nanocarriers and integrin-overexpressed tumor tissues. It has been generally validated that RGD modification can significantly boost the antitumor effect of drug delivery systems. In this chapter, the methods how to prepare and evaluate a RGD-mediated targeting drug liposome are presented. In order to facilitate longer circulation time in vivo, polyethylene glycol (PEG)-modified lipids are usually employed to construct the active targeting liposomes. Firstly, the protocols to synthesize the RGD-conjugated liposomal membrane materials based on the PEGylated lipids and the approaches to confirm successful conjugation of RGD to the lipids are described. Then the preparation methods of RGD-modified liposomes are introduced, including the thin film hydration, reverse evaporation, and extrusion method. Here two kinds of antitumor agents are chosen as model drugs and are described in detail how to prepare their respective liposomes. Doxorubicin (DOX), an antitumor anthracycline antibiotic from Streptomyces bacteria, can be loaded into liposomes using the pH-gradient method. pDP peptide, an antitumor D-peptide working by inhibiting the p53-MDM2 interaction, can be loaded into liposomes using the reverse evaporation method. The presence of RGD on the liposomal surface and the physicochemical properties of the resultant liposomes are characterized. Finally, the tumor targeting ability and antitumor efficacy of the liposomes are assessed in vitro and in vivo to exhibit the benefits of RGD modification.