Biomedical Engineering Reference
In-Depth Information
various fields ranging from drug/gene delivery to cellular imaging to develop-
ment of vaccines, antibacterial, antiviral and anticancer agents. (Aulenta et al.
2003; Stiriba et al. 2002; Patri et al. 2002; Boas and Heegaard 2004).
The unique molecular architecture of dendrimer macromolecules impart
those significantly improved physicochemical properties when compared to lin-
ear polymers. In solution, linear chains exist as random coils; while dendrimers
tend to stay as dense shells. Moreover, the exterior functional groups of den-
drimers impart them with properties of high solubility, miscibility and reactivity.
The structural versatility and controlled multivalence of dendrimers can be used
to perform multiple conjuagtion reactions to attach several drug molecules, tar-
geting moieties and solubilizing groups to the dendrimer periphery. Moreover,
dendrimers with low polydispersity contrarily to some linear polymers with dis-
tinct molecular weight can provide reproducible pharmacokinetic behavior. Such
interesting properties make dendrimers highly suitable for biological applica-
tions (Duncan et al. 2001).
2.1 Dendrimers as Drug Carriers
Polymeric nanocarriers hold great promise as delivery systems to increase the
solubility and circulation times of therapeutic cargo (Duncan 1992). Also, several
reports suggest the ability of polymer based carriers for drug delivery by passive
targeting to solid tumors. Increased permeability of tumor vasculature and poor
lymphatic drainage system enable enhanced accumulation of nanocarriers in
tumor region by a phenomenon termed the 'enhanced permeation and retention'
(EPR) effect (Matsumura and Maeda 1986). The monodispersity, multivalency and
unique structural properties of dendrimers make them prospective candidates for
anticancer drug delivery applications.
2.1.1 Noncovalent Encapsulation of Drugs
The well-defined, three-dimensional shape of dendrimers mediate formation of
internal nano-cavities which can act as centres to encapsulate guest molecules
by supramolecular host-guest interactions. Large number of functional groups
at the surface of high generation dendrimers can form a stearic shell separat-
ing the core from the exterior bulk to protect the entrapped guest molecules.
Such encapsulation of guest molecules by dendrimers is based on the idea of
“dendritic box”. In recent years numerous reports are available wherein high
generation dendrimers have been used for accommodation of anticancer drugs
under physiological conditions. However, in this approach it is difficult to con-
trol the release of drug molecules from the dendrimer core. Bhadra et al. (2003)
suggested that introduction of high molecular weight poly(ethylene) glycol
(PEG) chains on the dendrimer periphery for 5-fluorouracil (5-FU) delivery can
