DENDRIMERS – A RECENT
DRUG DELIVERY SYSTEM
Under the guidance of
Dr. K. H. Ramteke
Dept. of Pharmaceutics
Modern college of pharmacy (for ladies), Moshi, Pune 1
Varsha V. Awasarkar
M Pharm 1st
• Types of dendrimers
• Mechanism of drug release
• Synthesis of dendrimers
• Applications of dendrimers
• Literature survey
• To emphasize on dendrimeric drug delivery
• To focus on current applications of dendrimers.
• A suitable drug delivery system would protect the drug against degradation
and ensure that drug reaches proper permeability properties and further
provides a combined transportation and protection system against the
natural barriers, as done by the dendrimers. Dendrimers are highly defined
– Size: 1 -15 nanometers
– Very versatile surface functionalisation
– Synthetic: Practical and cost effective
– Well tolerated pharmaceutica.
• The term “Dendrimer” arise from two Greek word :
- “Dendron” meaning tree’
-“Meros” meaning part
• The dendrimers are also called as CASCADE MOLECULES or
• Dendrimers are hyper-branched, globular, monodisperse, three dimensional
nanoscale synthetic polymers, having very well defined size, shape and
definite molecular weight.
• Dendrimer is a nanoparticle (10-9
) and so has advantages over
microparticles or others due to its small size, easy uptake by cells (through
• They are branched macromolecules have a central core unit having a high
degree of molecular uniformity, narrow molecular weight, distribution,
specific size and shape characteristics, and a highly- functionalized,
• Dendrimers exhibit characteristics features of both molecular chemistry and
polymer chemistry. Molecular chemistry like properties are due to their step
by step controlled synthesis while it shows polymer chemistry like properties
as it is made up of monomers.
Components of a Dendrimer Structure:
Generation, Shell, Pincer, End group.
• Goals behind developing the dendrimers:
A) Modify/Improve the pharmacokinetic and pharmacodynamic
properties of a drug so that there is also an accretion in
B) Achieve the controlled and targeted release of drug restricted to
the area desired. 
• STRUCTURE: Dendrimers are built from a starting atom, such as
nitrogen, to which carbon and other elements are added by a
repeating series of chemical reactions that produce a spherical
• As the process repeats, successive layers are added, and the
sphere can be expanded to the size required by the investigator.
The result is a spherical macromolecular structure whose size is
similar to albumin and hemoglobin, but smaller than such multimers
as the gigantic IgM antibody complex. 6
1.1 STRUCTURE OF DENDRIMERS
7Figure 1: Schematic representation of the dendrimer typical structure.
Structure of Dendrimers possesses 3 distinct units:
A Central core unit.
Generations i.e. branches, which are radically “Meros” meaning part attached to
the central core.
Terminal functional group attached to the outermost series of branches.
Table 1: Properties of Dendrimer And Linear
Property Dendrimers Linear Polymers
1 Structure Compact and Globular Not compact
2 Shape Spherical Random coil
3 Architecture Regular Irregular
4 Synthesis Stepwise growth Single step
5 Crystallanity Non-crystalline and amorphous
Materials Lower glass
Materials -Higher glass
6 Aqueous solubility High Low
7 Nonpolar solubility High Low
8 Compressibility Low High 9
• PAMAM [Poly (amido amine)] dendrimers are spheroidal or ellipsoidal in shape.
These are most studied macromolecules and are commercially available.
• The divergent method is used for their synthesis where ammonia or ethylenediamine
is used as starting material.
• The high solubility and reactivity of these are due to presence of a number of
functional end groups and empty internal cavities.
• The conventional macromolecules have low amino group density as compared to
PAMAM dendrimers. 
• Products up to generation 10 (a molecular weight of over 9,30,000 g/mol) have been
obtained (by comparison, the molecular weight of human hemoglobin is
approximately 65,000 g/mol). PAMAM dendrimers are commercially available, usually
as methanol solutions
• Starburst dendrimers is applied as a trademark name for a sub-class of PAMAM
dendrimers based on a tris-aminoethylene-imine core. The name refers to the star
like pattern observed when looking at the structure of the high-generation dendrimers
of this type in two-dimensions.
Figure 2: 3 dimentional projection of dendrimer core shell architecture for G-Figure 2: 3 dimentional projection of dendrimer core shell architecture for G-
4.5 PAMAM Dendrimers4.5 PAMAM Dendrimers
Table 2: Types of dendrimers 
Types Definition Synthesis Example Applications
dendrimers possess amino
groups on the
Divergent Dendritech(USA) Material Science and
micelles consists of
PAMAM interiors and
SARSOX Nano-lithography Electronics,
Photonics Chemical catalysis
Precursor for honeycomb like
Poly-alkyl amines having
primary amines as end
groups and its
Interior consists of
Divergent Asramol by DSM
Material science and biology
Composed of a core
dendrimer with multiple
dendrimers at its periphery
Divergent Stratus® CS Acute
Diseased cell recognition
Diseased state drug delivery
Reporting location to
outcome of therapy
Types Definition Synthesis Example Applications
dendrimers built with two
segregated sites of
Structure-directing agent, Use
as polar part, cell and gene
structure of Water soluble
Biological and medical
based upon a polylysine
Convergent VivaGel Used in vaccines and
diagnostic research. Biological
carboxylic acid groups as
surface groups and
Convergent Frechet type
Drug carrier, Purifiers, Organic
synthesis, detecting agent,
Consists of mesogenic
divergent Polycanter liquid
Science and Engineering.
Metallo Dendrimers with Convergent Zinc Porphyrin Sensing Catalytic applications,
MECHANISM OF DRUG DELIVERY
Fig. A Dendrimer molecule with
Drug molecules loaded at terminal
surface of branches.
(electrostatic interactions or
covalent conjugate) . 
Fig. A Dendrimer molecule with
terminal drug molecules
encapsulated within branches.
(simple encapsulation) . 
• The dendrimer is assembled from a multifunctional core, which is
extended outward by a series of reactions, commonly a Michael
reaction. Each step of the reaction must be driven to full completion
to prevent mistakes in the dendrimer, which can cause trailing
generations (some branches are shorter than the others). Such
impurities can impact the functionality and symmetry of the
dendrimer, but are extremely difficult to purify out because the
relative size difference between perfect and imperfect dendrimers is
• Dendrimers are built from small molecules that end up at the
surface of the sphere, and reactions proceed inward building inward
and are eventually attached to a core. This method makes it much
easier to remove impurities and shorter branches along the way, so
that the final dendrimer is more monodisperse. However dendrimers
made this way are not as large as those made by divergent
methods, because crowding due to steric effects along the core is
Figure 9: Divergent synthesis of dendrimer 
Figure 10: Convergent synthesis of dendrimer 
Double Exponential and Mixed Method:
This is amixture of both divergent and convergent method.
In this method a single starting material is taken from which
two monomers are prepared by divergent and convergent
method. Then these two monomers are reacted together to
give an orthogonally protected trimer. This protecter trimer
may be use to repeat the growth process again. 
Figure 12: Combined Divergent-Convergent Method
DENDRITIC POLYMERS [4, 1]
• Spectroscopy UV-Visible, IR, NMR.
• Microscopy TEM , AFM, SEC.
• Rheology, physical properties DSC
• Scattering techniques
• Electrical techniques
• Determination of Melting Point
• Elemental Analysis (Nitrogen)
A) Medication to the affected part inside a patient's body directly
B) Controlled and sustained release of drugs can also be obtained
C) Drugs can be easily made to remain within layers of skin and not
penetrate in systemic circulation
D) Bypassing the gastric medium and hence the eschewing the
variation due to effect of gastric secretions.
E) Increase in therapeutic efficacy, decrease in side effects:
decreased clearance of drug via altered distribution of drug in
organs at site of localization and transportation due to controlled
and sustained release of the drug.
F) Relatively high drug loading.
G) Preservation of drug activity: as drugs can be incorporated into the
systems without any chemical reaction.
Dendrimer having – NH2 termini shows and generation dependent
cytotoxicity, hemolytic activity. Which are associated with their cationic
nature. The cytotoxicity is a function of surface charge, size and
concentration. The cytotoxicity and hemolytic activity of cationic.
Non-charged dendrimer are non-toxic and bioavailable.
• A) Dendrimers with positively charged surface groups-prone to destabilize
cell membranes and cause cell lysis.
• B) Generation dependent toxicity-higher generation dendrimers being the
• C) Degree of substitution, type of amine functionality is important- primary
amines being more toxic than secondary or tertiary amines. 
APPLICATIONS OF DENDRIMERS
1. Therapeutic Application:
-Dendrimer in photodynamic therapy
-Dendrimers for Boron Neutron capture therapy
2. Diagnostic Application:
-Dendrimers as MRI contrast agent
-Dendrimers as X-Ray contrast agent
-Dendrimer as molecular probe
3. Pharmaceutical Application:
-Dendrimers in pulmonary drug delivery
-Dendrimers in Transdermal drug delivery
-Dendrimers in ocular drug delivery
-Dendrimers in oral drug delivery
-Dendrimers for controlled release drug delivery
-Dendrimers in targeted drug delivery
-Dendrimers in gene delivery
-Dendrimers as solubility enhancer
-Cellular delivery using Dendrimers carrier
-Dendrimers based product in cosmetics
-Dendrimers based commercial products
4. Dendrimers in Gene Delivery
5. Dendrimers as Solubility Enhancer
6. Dendrimers as Cellular Drug Delivery CarrierDendrimers in
Targeted and Controlled Release Drug Delivery
7. Dendrimers in Cosmetics
8. Dendrimers as a light harvesting antennae 
Author Aim Method and materials Result
PAMAM G3.0, bovine serum
albumin (BSA), gold chloride
and Au foil.
Method- Bottom – up
synthesized which was
used as brachytherapy
hydrochloride 3 as analogue
of benzalkonium chloride,
NaOH in ethanol, carteolol.
New series of PH-
having one quaternary
ammonium salt as core
and carboxylic acid
terminal groups have
been synthesized from
generation 0 (3
terminal groups) to
generation 2 (12
Author Aim Method and materials Result
binding to cell
Peptide grade reagents,
resins and solvents were
used for SPPS (solid
phase peptide synthesis)
Method- M6 prototype, a
synthesized on a lysine
core which tethers four 10-
mer peptide chains in
lysine and positions
The two peptide
and SB105 A10, to
directly and almost
(HCMV) replication in
lithium aluminum hydride
D2 dendrimer gave
the best result; it
against MCF-7 cell
line with IC50 of 1.07
mg/mL and resistant
1.97%, the other two
dendrimers showed a
• PAMAM dendrimers are presented as nanocarriers drugs promising for the
coming years, since the multiple properties related to their three-
dimensional structure, as mono dispersity, versatility, biocompatibility and
other characteristics intrinsic which increase the solubility and activity of
these drugs linked these polymers, improving the bioavailability and reduce
the toxicity potential of many drugs.
• The drug can be linked to the dendrimers by covalent bonds, electrostatic
interactions, or by encapsulation, and the choice of the interaction fits the
• As a flexible and excellent carrier, the dendrimers can be carefully designed
for the delivery of biomolecules to the desired target tissue, which allows the
use of lower doses, although effective in therapy.
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