1. DENDRIMERS By: S.R.Rashmi (B.Pharma) Kalinga University, New Raipur 2.The word "dendrimer" originated from two Greek words, dendron: meaning tree, meros- meaning part or segment. 3. Dendrimers possess three distinguished components, namely (i) An initiator core. (ii) Interior layers:- composed of repeating units, radically attached to the interior core(generations). (iii) Exterior layers attached to the outermost interior generations (terminal functionality). 4. Need of Dendrimers: Nano-particle drug-delivery systems are most popular one. However reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, haemolytic toxicity, cytotoxicity, restrict the use of these nanostructures. These are overcome by surface engineering the dendrimes such as Polyester dendrimer, Glyco-dendrimers, PEGylated dendrimers etc. The bioactive agents can be easily encapsulated into the interior of the dendrimers. or Chemically attached i.e. physically adsorbed on to the dendrimer surface. 5. Types of Dendrimers: 1)PAMAM Dendrimers2) PAMAMOS Dendrimers3) PPI Dendrimers4) TECTO Dendrimers5) MULTILINGUAL Dendrimers6) CHIRAL Dendrimers7) HYBRID Dendrimers linear polymers8)AMPHIPHILIC Dendrimers9) MICELLAR Dendrimers10) MULTIPLE ANTIGEN PEPTIDE Dendrimers11) FRECHET-TYPE Dendrimers 6. Methods of Synthesis: Divergent method: Dendrimers starts from the central core and extends toward the surface i.e. diverging into space. Two step process:Activation of functional surface groups,Addition of branching monomers units. 7. Convergent Method: Dendrimer starting from the end groups and progressing inwards. When the growing wedges are enough large, attached to a suitable core to give a complete Dendrimer. 8.Combined Method: This approach allows the preparation of monomers for both convergent and divergent growth from a single starting material 9. Mechanism of drug Loading : Simple encapsulation:-It directly encapsulates guest molecules into macromolecule interior. Electrostatic interaction:-Surface functional groups enhances solubility of hydrophobic drugs by electrostatic interaction e.g. Ibuprofen, ketoprofen, indomethacin. Covalent conjugation:-The drug is covalently bound to dendrimers & its cleavage occurs via chemical or enzymatic cleavage of hydrolytically labile bonds. It allows tissue targeting & controlled delivery as drug-dendrimer conjugate diffuse slower than the free. 10. Applications of Dendrimers: Dendrimers in biomedical field, Anticancer drugs, Dendrimers in drug delivery, Transdermal drug delivery, Dendritic sensors, Dendrimers used for enhancing solubility, Dendrimers as magnetic resonance imaging contrast agents 11. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER-2 positive breast cancer 12. When a cancer is HER2-positive, it means that the cancer cells make too much HER2 protein, which can cause tumors to grow more rapidly than with other forms of breast cancer.

1. By: S.R.Rashmi (B.Pharma)
Kalinga University,New
Raipur

2. dendron: meaning tree,
meros- meaning part or segment.
The word "dendrimer" originated from two Greek
words,

3. (iii) Exterior layers attached to the outermost interior generations
(terminal functionality).
Dendrimers possess three distinguished components,
namely
(i) An initiator core.
(ii) Interior layers:- composed of repeating units, radically attached to
the interior core(generations).

4. The bioactive agents can be easily encapsulated into the interior of the
dendrimers.
or
Chemically attached i.e. physically adsorbed on to the dendrimer
surface.
Need of Dendrimers:
Nano-particle drug-delivery systems are most popular one.
However reticuloendothelial system (RES) uptake, drug leakage,
immunogenicity, haemolytic toxicity, cytotoxicity, restrict the use of
these nanostructures.
These are overcome by surface engineering the dendrimes such as
Polyester dendrimer, Glyco-dendrimers, PEGylated dendrimers etc.

5. 1)PAMAM Dendrimers
2) PAMAMOS Dendrimers
3) PPI Dendrimers
4) TECTO Dendrimers
5) MULTILINGUAL Dendrimers
6) CHIRAL Dendrimers
7) HYBRID Dendrimers linear polymers
8) AMPHIPHILIC Dendrimers
9) MICELLAR Dendrimers
10) MULTIPLE ANTIGEN PEPTIDE
Dendrimers
11) FRECHET-TYPE Dendrimers
Types of Dendrimers:

6. Methods of Synthesis:
Dendrimers starts from the central core and extends toward
the surface i.e. diverging into space.
Two step process:
• Activation of functional surface groups
• Addition of branching monomers units.

7. Dendrimer starting from the end groups and progressing inwards.
When the growing wedges are enough large, attached to a suitable
core to give a complete Dendrimer.

8. This approach allows the preparation of monomers for both
convergent and divergent growth from a single starting material

9. Covalent conjugation:-The drug is covalently bound to
dendrimers & its cleavage occurs via chemical or enzymatic
cleavage of hydrolytically labile bonds. It allows tissue
controlled delivery as drug-dendrimer conjugate diffuse slower
than the free.
Simple encapsulation:-It directly
encapsulates guest molecules into
macromolecule interior.
Electrostatic interaction:-Surface
functional groups enhances solubility
of hydrophobic drugs by electrostatic
interaction e.g. Ibuprofen, ketoprofen,
indomethacin.
Mechanism of drug
Loading :

10. Applications of Dendrimers:
• Dendrimers in biomedical field
• Anticancer drugs
• Dendrimers in drug delivery
• Transdermal drug delivery
• Dendritic sensors
• Dendrimers used for enhancing
solubility
• Dendrimers as magnetic resonance
imaging contrast agents

11. Trastuzumab-grafted
PAMAM dendrimers
for the selective
delivery of
anticancer drugs to
HER-2 positive
breast cancer

12. When a cancer is HER2-positive, it means that the cancer cells
make too much HER2 protein, which can cause tumors to
grow more rapidly than with other forms of breast cancer.

13. • Trastuzumab (Herceptin)
• Pertuzumab (Perjeta)
• Neratinib (Nerlynx)
Drugs that target the HER2 proteins
are the primary treatment for this
type of breast cancer
• Anthracyclines, such as doxorubicin (Adriamycin) and epirubicin
(Ellence)
• Taxanes, such as paclitaxel (Taxol) and docetaxel (Taxotere)
• 5-fluorouracil (5-FU) or capecitabine.
• Cyclophosphamide (Cytoxan)
• Carboplatin (Paraplatin)
Chemotherapy drugs used for breast cancer are:

14. Trastuzumab (TZ)
+
Docetaxel (DTX)
Altough some drugs are already available, most cause serious
side effects because they also impact healthy cells. To avoid this
unwanted response the researchers combined two existing
drugs in a clever new formulation.

15. Trastuzumab (TZ)
Trastuzumab is an antibody that binds to HER-2 cells, it is selective and
toxic on its own but it works much better in combination with other
chemotherapy

16. Docetaxel (DTX)
Docetaxel on the other hand is very toxic
but it doesn’t discriminate between
healthy and cancerous cell

17. To try and get the best of both the drugs, both the molecules
were brought together with dendrimers, tiny synthetic polymers
with the branching tree like structure.

18. DTX is shielded from healthy cells , while TZ is free
to target cancerous cells.