The term “dendrimer” is derived from the Greek words “dendron” means tree or branches and “meros” means part. It was introduced in 1984 by Donald A. Tomalia.
Highly branched macromolecule Capable of encapsulating High loading capacity Backbone of Carbons or Nitrogens Monodisperse and controllable Highly stable Low immunogenicity and toxicity
The structure is highly defined and organized. Dendrimers posses 3 distinguishing architectural components: 1) Initiator core. 2) Interior layers. 3) Terminal functionalities.
They start from a core molecule with at least 3 chemically reactive arms. To these arms, branches are attached. - Repeated many time
•Branches extend from core to periphery.•Large dendrimers adopt a globular shape, inwhich all bonds converge to a focal point•“Star Burst Effect”.
Monodispersive. Exact same molecular weight and structure. Peculiar behaviour of intrinsic viscosity
The terminal groups affect solubility and viscosity The outer surface area of the molecule increases with the number of generations There are void space within the molecule. These unique geometries give the molecule special properties such as ability to entrap foreign molecules (drugs).
Two common delivery systems 1. Liposome 2. Polymers Poor stability Difficulty in targeting Toxicity Reduces circulation time
ENTANG L EMENTS Dendrimers Linear Polymers less entanglements more entanglement.
ArchitectureDendrimers Linear PolymersDendritic architecture Linear architecturehas been shown as has not been shownelegant, uniform, as elegant and can bespherical and as visualized as“green peas” “ cooked spaghetti”.e.g. e.g Polyether linearPolyether dendrimer. polymer
Size / PolydispersityDendrimers L inear PolymersHave certain size, Does not havemonodisperse certain size and are , . usually poly disperse.
SolubilityDendrimers Linear PolymersMore solubility in Less soluble thanorganic solvent in analogous dendrimercomparison to the in organic solventanalogous linear e.g. phenylene linearpolymer e.g. analogue.1, 3, 5 phenylenebased dendrimer.
SYMMETRYDendrimers Hyper branched PolymersMonodispersible regular P olydispersible , neitherand highly symmetrical. regular nor symmetrical. SYNTHESISObtained by careful , Obtained in a single stepstepwise growth of by poly condensation ofsuccessive an A2B monomer.generations.
There are two defined methods of dendrimer synthesis: -Divergent -Convergent growth approach. In the divergent method the molecule is assembled from the core to the periphery.
In the divergent method, the surface groups initially are non-reactive or protected species which are converted to reactive species for the next stage of the reaction. In the convergent approach the opposite holds, as the reactive species must be on the focal point of dendritic wedge.
This type of synthesis involves two steps:( 1 ) The activation of functional surface groups.( 2 ) Addition of branching monomer units.
ADVANTAGE The advantage of this method is the ability to modify the surface of the dendrimer molecule.
In successive generation growth, side reactions and incomplete additions become more apparent. This is due to steric hindrance. The overall yield is considerably small The outer generation has only one kind of functional group.
•The difficulty of many reactions that have to beperformed on one molecule is overcome bystarting the synthesis at the periphery and endingat the core.•In this method, growth begins at what willbecome the periphery of the final macromoleculeand proceed inward, the final reaction beingattachment to a polyfunctional core.
It involves the attachment of the outermost functional group to an inner generation and the attachment of the inner generation to the core. The structural units before the final attachment to the core is called the wedge. Usually 3 to 4 wedges attach to the core. Each wedge can have different functional groups at periphery.
Advantage of this method over “divergent growth” approach :- control over surface functionality. Ease for purification.
More susceptible to steric inhibition at the focal point group. This effectively limits the size of the macromolecules that may be prepared in conventional fashion..
Convergent approach affords better control to obtain a better dendrites architecture than the divergent approach. Divergent approach is for large scale production. Both involve stepwise processes that are tedious and time consuming.
The well-defined structure, compact globular shape, size monodispersity and controllable „surface‟ functionalities of dendrimer makes them excellent candidates for evaluation as drug carriers. They can be used as drug delivery agents in 2 ways (1) Drugs molecules can be physically entrapped inside the dentritic structure. (2) Drug molecules can be covalently attached onto surface or other functionalities to afford dendrimer drug conjugates.
The internal „cavity‟ of the dendritic structure can be used for the entrapment drugs.( I ) FIRST STRATEGY: - First strategy for the encapsulation of the guest molecules in dendrimers is physical encapsulation.
Held by Van der Waals or dipole moments Carrier compounds do not have to be solublized
1. Targeted delivery would be difficult to achieve because drug release occurred by dialysis.2. Difficult to make universal for all drugs, because encapsulation by the dendrimer varied significantly depending on drug and the dendrimer structure.
The second strategy for the encapsulation of guest molecules in dendrimers is based on multiple non- covalent chemical interactions, such as hydrogen bonding between guest molecules and dendritic structure. Sustained release is possible.
The third and the most easily implemented startegy for the encapsulation of drug molecules in dendrimers is making use of hydrophobic interactions Newkome et al. prepared dendritic macromolecules with a hydrophobic interiors and hydrophilic chain ends. These molecules were said to behave as unimolecular micelles capable of solubilizing various hydrophobic
e.g.:- Poly (aryl ether) dendrimers bearing carboxylic groups as chain ends are able to enhance the water solubility of the hydrophobic compound such as pyrene and anthracene.
Higher generation dendrimers have a greater number of end groups that can be functionalized Longer retention time in blood – PEG Targeting – ability to attach to certain tissues or active sites Imaging – Fluorescence, MRI, or X-ray