(165f) Prodrugs AS Multifunctional Drug Nanocarriers

    Nanomedicines mainly contain two parts, the inert carriers and the bioactive agents. The carriers are typically inert and their only role is to make the vehicles. For instance, the lipid and cholesterol in conventional liposomes have no other functions but to make the vesicles carrying drugs. The amphiphilic block copolymers used to make nanoparticles are just for forming the core-shell structure encapsulating hydrophobic drugs in the core. But generally, the carriers are the major while the bioactive agents are minor components in nanomedicine. For instance, in nanoparticles or liposomes, the drug contents are generally not greater than 10%. Polymer–drug conjugates only contain a few percents of drugs to keep the conjugates water-soluble. Therefore, large amounts of carriers are needed to deliver required doses of drugs, bringing difficulty and problems for parenteral biodelivery. Furthermore, the multistep fabrication processes of most nanomedicines raise batch-to-batch variation and quality concerns.Herein, we demonstrated a new concept employing the drug molecules themselves as components of nanocarriers to substantially increase the drug loading content, minimize the use of inactive materials, and suppress the premature burst drug release.

   Taking advantage of the hydrophobicity of CPT, two CPT molecules were conjugated to a very short PEG chain (OEG), forming an amphiphilic phospholipid-like molecule, OEG-DiCPT (Figure 1). Once in water OEG-DiCPT formed stable liposome-like nanocapsules with a fixed CPT loading content as high as 58 wt% without burst release in aqueous solution. OEG-DiCPT itself was a prodrug releasing CPT once inside cells, which showed high in vitro and in vivo antitumor activity. Meanwhile, the formed nanocapsules could be loaded with a water-soluble drug such as DOX·HCl with high loading efficiency. The DOX·HCl–loaded nanocapsules delivered two anticancer drugs producing a synergetic cytotoxicity to cancer cells. Similarly, curcumin was used to surfactant-like prodrug formed nanoparticles as carriers of curcumin itself and other drugs and polymer-drug conjugates with high drug loading contents.