Dendrimers differ from conventional polymers, in that they are nanoscopic in size (1–100nm), well defined, spherical, possess a high degree of molecular uniformity,

and bear ample number of modifiable surface groups [82]. The structural configuration of dendrimers also confers a large drug loading by various techniques such as adsorption to the surface (ionic interaction), encapsulation within hydrophobic microcavities inside branching clefts or direct covalent conjugation to the surface functional groups. These unique properties make dendrimers a desirable platform for concurrent delivery of water-soluble and -insoluble drugs [14, 104]. Examples of dendrimer-based PKC inhibitor Combination drug delivery Inhibitors,research,lifescience,medical systems that Inhibitors,research,lifescience,medical are currently investigated are listed in Table 4. For example, Ren et al. have developed a poly (amidoamine) (PAMAM) dendrimer for simultaneous co-delivery of gene therapy and chemotherapy agents. 5-fluorouracil (5-FU) was encapsulated in the cavities of the dendrimer core via hydrogen bonding while an antisense microRNA (miR-21) was complexed to the surface through cationic surface charge-based interaction [78]. Successful synchronous delivery of the two therapeutic agents was achieved resulting Inhibitors,research,lifescience,medical in synergistic anticancer efficacy, apoptotic activity, and decreased migration ability of the cancer cells compared to each agent alone. In another example Kaneshiro and

Lu developed a targeted nanoglobular dendrimer based on a poly(l-lysine) core for intracellular codelivery of doxorubicin (Dox, chemotherapeutic) and siRNA (nucleic acid) [81]. An endothelial

targeting peptide c(RGDfK) was conjugated to the dendrimer surface via a PEG spacer. Dox was covalently conjugated while siRNA was complexed Inhibitors,research,lifescience,medical to the dendrimer. The targeted dendrimer dual agent delivery system resulted in significantly higher gene silencing efficiency in U87 glioblastoma cells than dendrimer-Dox conjugates or dendrimer siRNA complexes [81]. Lee and coworkers have developed a targetable dendrimer for combination chemoimmunotherapy delivery. A single-stranded Calpain DNA-A9 PSMA (prostate-specific Inhibitors,research,lifescience,medical membrane antigen) RNA aptamer hybrid was conjugated to a PAMAM dendrimer as the tumor targeting moiety. This system was complexed with a plasmid bearing unmethylated CpG that acts as both an immune-stimulating agent and a carrier of the drug, Dox. The dendrimer-based conjugate showed greater antitumor efficacy with much lower toxicity than the same dose of free Dox or aptamer-free dendrimer conjugate in murine tumor models [79]. Figure 3 Combination drug delivery systems based on dendrimers: concurrent delivery of water-soluble and -insoluble drugs by adsorption to the surface (ionic interaction), encapsulation within hydrophobic microcavities inside branching clefts or direct covalent … Table 4 Combination drug delivery systems based on dendrimers. 4.3.