DENDRIMERS FOR DRUG DELIVERY

Dendrimers

Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units

- Not more that 15 nm in size, Mol. Wt very high

- Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers)

Dendrimers

The first dendrimers were synthesized

by Tomalia and co-workers at Dow

Chemical in the early 1980s in parallel

with Newkome’s ‘arborol’ systems.

In 2008 there were over 10 000

scientific reports and 1000 patents

dealing with dendritic structures.

Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm

Dendritic polymers

Dendritic materials comprise sub-classes such as dendrimers dendrons hyperbranched polymers dendrigraft polymers dendronized polymers

Dendritic polymers exhibit very different properties compared to their linear analogues.

Vogtle laboratory in 1978 reported the first concept of branching by repetitive growth

Dendritic Family

Structural Components of Dendrmers

Dendrigraft polymers

Dendrigraft polymers, sometimes referred to as arborescent

polymers, are a relatively new addition to the dendritic family,

combining features of dendrimers and hyperbranched

polymers with linear polymers.

Dendrigraft polymers are grown in generations, much like

dendrimers, but the repeating unit is an oligomer or a polymer

chain, rather than a small monomer unit.

As dendrigraft polymers flexible polymers with very high

molecular weights are obtained rapidly.

Examples of dendrigraft polymers are:

Comb-bursts

arborescent polybutadiene,…

Dendronized polymers

Dendronized polymers, sometimes termed ‘‘rod-shaped polymers’’, are structures having a linear backbone with dendritic sidechains.

Dendronized polymers are a sub-class of comb-polymers where the ‘‘comb’s teeth’’ are dendrons instead of linear polymer chains.

Fully stretched out dendronized polymers are rod-like cylindrical polymers (‘‘nanotubes’’) and are believed to have new and interesting properties, since they have dimensions reminiscent of several biological functional units, such as the mosaic virus (lengths up to 400 nm and diameters up to 6 nm).

Dendronized polymers have exceptionally high aspect ratio compared to the globular dendrimers, i.e. they are not only molecular objects; they are also form-anisotropic nanoscopic objects.

Examples: PAMAM-based dendronized polymers, P(bis-MPA)-based dendronized polymers, Fre´chet-type dendronized polymers, Percec-type dendronized polymers, ...

Applications in Pharmaceutical Industry

drugs e.g. VivaGel®active SPL7013 drug delivery – Small molecules proteins tissue targeting Drug solublization siRNA/DNA delivery diagnostics & materials applications

Applications in Drug/Protein Delivery

Improved efficacy of drugs Extension of drug half-life Reduced toxicity Active or passive targeting

(e.g. EPR*) Product lifecycle

management Improved solubility of drugs Drug “rescue”

Improved Drug Solubility

Utilizing a dendrimer construct the aqueous solubility of the drug Paclitaxel was increased >9,000X.

Paclitaxel aqueous solubility 0.8 mg/mL

Drugs Delivered Through Dendrimers