Biomedical Engineering Reference
In-Depth Information
Fig. 6
G4.0 PAMAM dendrimers stochastically modified with DOX through a non-cleavable or
cleavable bond. Adapted from Caminade et al., with permission from Royal Society of Chemistry.
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conjugates were internalized by Skov-3 cells (ovarian carcinoma) but only cleav-
able PPCD conjugates were able to release DOX to induce cell death while PPSD
conjugates displayed no toxic effects (Zhu et al. 2010).
Use of Janus dendrimers (two types of terminal functions in two different areas
of the surface of the dendrimer) for the formulation of dendrimer-drug conjugates
has been described (Caminade et al. 2012). An asymmetric biodegradable polyes-
ter dendrimer (modified with PEG derivatives) conjugated to DOX with cleavable
acyl hydrazone linkages has been used for in vivo assessment in mice bearing C-26
colon carcinoma tumors (Fig.
7
). A single intra venous (i.v.) injection of the Janus
dendrimer-DOX conjugates was able to release DOX (through cleavage of pH sensi-
tive acyl hydrazone linker) causing complete tumor regression and 100 % survival
of mice, whereas with free DOX or Janus dendrimer-DOX conjugate linked through
stable carbamate bond, no cure was achieved. Ability of dendrimer to favoura-
bly modulate the pharmacokinetics of conjugated DOX can be held worthy of the
remarkable antitumor activity of dendrimer-DOX conjugate (Lee et al. 2006).
All the above stated examples of dendrimer-drug conjugates involve use of pH
sensitive linkages, i.e. release of attached drug occurs specifically under acidic
conditions. Such linkers are expected to be cleaved more rapidly in cancer cells
