Dendrimers in Pharmaceutical Industry

Some of you might have heard of polymers. But have you ever heard of dendrimers? Dendrimers are monodisperse, highly branched, macromolecules with a tree-like structure; (unlike linear polymers). The name "dendron” comes from Greek, which means tree, due to their branched structure. Owing to their unique 3D structure, dendrimers have very special chemical and physical properties. One of the most special characters of dendrimers is having a cavity within the structure, which can be used to load different molecules for different purposes. The pharmaceutical industry has paid attention to dendrimers due to this loading property, where dendrimers can be used as drug carriers to the body, which can carry drugs to targeted organs or cells.

Special physical characters of dendrimers are generation, core coordination, and terminal groups. Generation of a dendrimer is defined as the number of branching units along one branch. Core-coordination is the number of branches that can form by bonding the repeating groups to the core. Terminal groups are the end groups of the dendrimer. According to the hydrophobic and hydrophilic nature of terminal groups (i.e. - their love or hate towards water), different types of dendrimers can be formed for different purposes. Also, different dendrimers can have different generation numbers, core coordination, and terminal groups, in accordance with their purpose.
Figure - Structure of a dendrimer
Dendrimers tend to form a tightly packed ball inside solutions. The viscosity of a solution containing dendrimers has a very lower value, compared to the solutions of other polymers. This viscosity starts to increase with generation (up to the fourth generation) and then gradually decrease. Because of having higher number of chain ends, it has high solubility and reactivity compared to other polymers.

There are different types of dendrimers depending on their synthesis methods and physical characteristics. (e.g: Pamam Dendrimer, Pamamos Dendrimer, PPI Dendrimer, etc.) With the help of nanotechnology and chemistry, many technologies have developed in the fields of Targeted and controlled drug delivery, Medical devices, Cell/tissue engineering, Gene delivery, Molecular-tags, Biosensors, bioanalysis. Dendrimers, which is a nano-level drug delivery system, has various applications in pharmaceuticals, such as enhancing the delivery of DNA and oligonucleotides, targeting drugs to specific organs or cells in the body, increasing the solubility of sparingly soluble drugs and as drug delivery agents.

Dendrimers are already being used in oral drug delivery(e.g: Doxorubicin, Naproxen) where the drug is taken through mouth cavity, ocular drug delivery (e.g: carteolol , pilocarpine) where the drug is given to the body through the eyes, transdermal drug delivery (e.g: Indomethacin, Non-steroidal anti-inflammatory agents ) where the drug is applied to unbroken skin and pulmonary delivery of drugs (e.g: Enoxaparin, Flurbiprofen) where the drug is inhaled through mouth and deposited in lower airways of the body.

Due to the hydrophobic interior (the inner structure of the dendrimer is repelled from water) and hydrophilic exterior (the outer structure of the dendrimer is attached to water), dendrimers show micelle like behavior. This helps to increase the solubility of low soluble drugs. Some dendrimers (eg-Polyamidoamine (PAMAM) dendrimers) can enhance the solubility of sparingly soluble drugs and to act as delivery agents for DNA and oligonucleotides to the nucleus of a cell. This method is very helpful in gene technology, because the dendrimers have high efficiency and are biodegradable inside the body. PAMAM dendrimers can capture the drugs, which are toxic to the body when they are in high concentrations, and release them slowly to the body, which will in turn reduce the toxicity of the drug. They also help the drugs to work better on microbial and fungal cells. PAMAM dendrimers with poly((l-glutamic acid) give biodegradable polymers enhanced targeting ability, making them even more efficient drug carriers. Dendrimers are a good agent for the delivery of small molecules, such as DNA and organic molecules. It is stated that some dendrimers also enhance the transfection efficiency of DNA. All in all, dendrimers have already being playing a vital role in our healthcare, without us knowing about it.

This article was sent in by Waruni Kulathunga. She is a demonstrator at Department of Chemistry, University of Peradeniya, and has a BSc (special) degree in Chemistry. You can reach her by Email.

References:

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