Application of Nanotechnology in Diagnosis and Therapeutics
425
(PAMAM) is the most vividly used dendrimer that is highly biocompatible and watersoluble. In one of the studies, it was reported that hydrophobic molecules can be easily
attached at the terminal ends or entrapped in the middle of the polymer. Further, in
another study it was found that in the presence of dendrimers, the water insoluble aceclofenac was able to easily solubilize upon increasing the pH of the solution. This was
attributed to the fact that the terminal groups of dendrimers reacted with the carboxyl
group of aceclofenac (Patel et al. 2011). Similarly different drugs are being used for
its delivery in vitro for the treatment of several diseases including inflammatory disease, cancer, and infectious diseases. Inflammatory diseases such as arthritis, acute
lung inflammation, and retinal degeneration are widely investigated fields. Folate
(FA) and methotrexate (MTX) conjugated dendrimer (G5-FA-MTX) were used in a
study to ameliorate collagen-induced arthritis in a rat model. The cellular uptake was
mediated by receptor-mediated endocytosis and there was significant decrease in the
ankle swelling, paw volume, cartilage damage, and bone resorption (Thomas et al.
2011). Similarly, in another study azabisphosphonate (ABP)-capped dendrimer was
used for the treatment of rheumatoid arthritis in a mice model. The outcome showed
positive results characterized by normal synovial membranes, reduced inflammatory cytokines, and absence of cartilage destruction as well as erosion. The study
showed promising role of dendrimers in rheumatoid arthritis (Hayder et al. 2011).
Another group of disease described in the earlier sections is cancer. Dendrimers have
also been investigated for the delivery of anticancer agents such as cisplatin and doxorubicin. The dendrimer-platinate (Pt) conjugate showed selective accumulation in
the tumor tissue via EPR effect with a 50-fold increase in the area under the curve
in relative to free cisplatin. Also, the dendrimer-Pt showed less toxicity (Malik et al.
1999). A commonly used anticancer drug such as doxorubicin was also formulated
with dendrimer. PEGylated polylysine dendrimers with 50% surface conjugation
of doxorubicin through acid-labile 4-hydrazinosulfonyl benzoic acid linker showed
efficient antitumor efficacy in walker 256 rat tumor model and human MDA-MB231
xenograft in mice. A direct comparison was made with liposomal formulation that
showed reduction in the tumor proliferation >75% in the doses ranging between 2
and 10 mg/Kg with a better tolerance in both the rats (Kaminskas et al. 2012). Infectious diseases such as those induced by E. coli and HIV are also investigated for its
treatment using dendrimer. The study showed the in vivo antimicrobial efficacy of
PAMAM dendrimers and its mechanism. It was observed that upon cervical administration generation-4 neutral dendrimer (G(4)-PAMAM-OH) showed considerable
effect on the E.coli induced uterine infection in Guinea pig model with chorioamnionitis. The collection of amniotic fluid after treatment showed decrease in the
number of E.coli. The possible antibacterial mechanism proposed was its ability to
bind to the polyanionic lipopolysaccharide or formation of hydrogen bonds with the
O-antigens of E.coli. Further, third mechanism could be its ability to chelate divalent
ions in outer cell membrane. It is to be noted that this was the first study showing
G(4)-PAMAM-OH dendrimer as an antibacterial agent (Wang et al. 2010). Similarly,
SPL7013 Gel (VivaGel(®)), a microbicide was developed for prevention of HIV and
HSV. The study showed potential antiviral activity with vaginal administration of
425
(PAMAM) is the most vividly used dendrimer that is highly biocompatible and watersoluble. In one of the studies, it was reported that hydrophobic molecules can be easily
attached at the terminal ends or entrapped in the middle of the polymer. Further, in
another study it was found that in the presence of dendrimers, the water insoluble aceclofenac was able to easily solubilize upon increasing the pH of the solution. This was
attributed to the fact that the terminal groups of dendrimers reacted with the carboxyl
group of aceclofenac (Patel et al. 2011). Similarly different drugs are being used for
its delivery in vitro for the treatment of several diseases including inflammatory disease, cancer, and infectious diseases. Inflammatory diseases such as arthritis, acute
lung inflammation, and retinal degeneration are widely investigated fields. Folate
(FA) and methotrexate (MTX) conjugated dendrimer (G5-FA-MTX) were used in a
study to ameliorate collagen-induced arthritis in a rat model. The cellular uptake was
mediated by receptor-mediated endocytosis and there was significant decrease in the
ankle swelling, paw volume, cartilage damage, and bone resorption (Thomas et al.
2011). Similarly, in another study azabisphosphonate (ABP)-capped dendrimer was
used for the treatment of rheumatoid arthritis in a mice model. The outcome showed
positive results characterized by normal synovial membranes, reduced inflammatory cytokines, and absence of cartilage destruction as well as erosion. The study
showed promising role of dendrimers in rheumatoid arthritis (Hayder et al. 2011).
Another group of disease described in the earlier sections is cancer. Dendrimers have
also been investigated for the delivery of anticancer agents such as cisplatin and doxorubicin. The dendrimer-platinate (Pt) conjugate showed selective accumulation in
the tumor tissue via EPR effect with a 50-fold increase in the area under the curve
in relative to free cisplatin. Also, the dendrimer-Pt showed less toxicity (Malik et al.
1999). A commonly used anticancer drug such as doxorubicin was also formulated
with dendrimer. PEGylated polylysine dendrimers with 50% surface conjugation
of doxorubicin through acid-labile 4-hydrazinosulfonyl benzoic acid linker showed
efficient antitumor efficacy in walker 256 rat tumor model and human MDA-MB231
xenograft in mice. A direct comparison was made with liposomal formulation that
showed reduction in the tumor proliferation >75% in the doses ranging between 2
and 10 mg/Kg with a better tolerance in both the rats (Kaminskas et al. 2012). Infectious diseases such as those induced by E. coli and HIV are also investigated for its
treatment using dendrimer. The study showed the in vivo antimicrobial efficacy of
PAMAM dendrimers and its mechanism. It was observed that upon cervical administration generation-4 neutral dendrimer (G(4)-PAMAM-OH) showed considerable
effect on the E.coli induced uterine infection in Guinea pig model with chorioamnionitis. The collection of amniotic fluid after treatment showed decrease in the
number of E.coli. The possible antibacterial mechanism proposed was its ability to
bind to the polyanionic lipopolysaccharide or formation of hydrogen bonds with the
O-antigens of E.coli. Further, third mechanism could be its ability to chelate divalent
ions in outer cell membrane. It is to be noted that this was the first study showing
G(4)-PAMAM-OH dendrimer as an antibacterial agent (Wang et al. 2010). Similarly,
SPL7013 Gel (VivaGel(®)), a microbicide was developed for prevention of HIV and
HSV. The study showed potential antiviral activity with vaginal administration of