Dendrimers

Dendrimers are versatile, derivatizable, well-defined, compartmentalized chemical polymers with sizes and physicochemical properties similar to biomolecules such as proteins (100). Dendrimers evolve from the cross-linked and branched polymers (Fig. 3). There are numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers can be used for antibacterial and antiviral therapy, and have shown potential as drug or gene delivery devices in anticancer therapy. Additionally, dendrimers can serve as "glycocarriers" for the controlled multimeric delivery of biologically relevant carbohydrate moieties, agents that are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes (102).

A star polymer composed of amphiphilic block copolymer arms has been synthesized and characterized. The core of the star polymer is polyamidoamine (PAMAM) dendrimer, the inner block in the arm is lipophilic poly(epsilon-caprolactone) (PCL), and the outer block in the arm is hydrophilic PEG. A loading capacity of up to 22% (w/w) into the star-PCL-PEG polymer was achieved with etoposide, a hydrophobic

Figure 3 Evolution of dendrimers from synthetic polymers: (I) linear, (II) cross-linked (bridged), (III) branched, (IV) structure-controlled dendritic polymers, and finally, dendrimers. Source: Reprinted from Ref. 101 with permission from Elsevier.

anticancer drug. A cytotoxicity assay demonstrated that the star-PCL-PEG copolymer is nontoxic in cell culture. This type of block copolymer can be used as a drug delivery carrier (103). Paclitaxel, a poorly soluble anticancer drug, was covalently conjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis(PEG) polymer for the potential enhancement of drug solubility and cytotoxicity. Cytotoxicity increased by 10-fold with PAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug (104). Dendrimers based on melamine can reduce the organ toxicity of solubilized cancer drugs administered by intraperitoneal injection (105).

Peptide dendrimers are radial or wedge-like branched macromolecules consisting of a peptidyl branching core and/or covalently attached surface functional units. The multimeric nature of these constructs, the unambiguous composition and ease of production make this type of dendrimer well suited to various biotechnological and biochemical applications. Applications include use as biomedical diagnostic reagents, protein mimetics, anticancer and antiviral agents, vaccines and drug and gene delivery vehicles (106).

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