Dendrimers: research fascination or commercial reality?
Confidence in the use of dendrimers for drug delivery was boosted in May 2008, with the announcement of positive clinical
trial results by Starpharma Holdings Limited, demonstrating that its topical vaginal microbicide gel product (3% SPL7013 Gel)
was found to be safe and well tolerated in sexually abstinent women when administered twice daily for a 14-day treatment period
(57). In this case, dendrimers act by binding to the gp120 glycoprotein binding sites on the HIV virus, which prevents the
virus from attaching to the T-cells, thereby blocking infection (see Figure 2). This topical vaginal microbicide is designed
to prevent transmission of sexually transmitted infections, including HIV and genital herpes, and uses dendrimers as an active
agent. This was the first dendrimer-based product to be approved by regulatory authorities for human clinical testing under
an investigational new drug application for prevention of genital herpes. It was reported that no participants showed untoward
effect from using the fourth-generation polylysine dendrimer-based gel. In addition, no absorption of the active agent used
in the gel was found in the systemic blood circulation after vaginal topical application. Also, vaginal microflora was found
to be unaffected after VivaGel (Starpharma) treatment. Currently, the topical vaginal gel is in Phase II human clinical trials.
Figure 2: Schematic mechanism of a dendrimer as a topical vaginal microbicide. HIV viral particles (black) attach to T-cell
receptors on the surface of the T-cells (blue) as an initial step in infection (left, without dendrimer gel application).
Dendrimers bind to the surface of the HIV particles and block attachment, reducing or preventing infection (right, with dendrimer
gel application). (FIGURE 2 IS COURTESY OF THE AUTHORS.)
Other dendrimer-based products that are in process of reaching commercial reality include Avidimers (Avidimer Therapeutics, Ann Arbor, MI) for cancer prevention and treatment and gadolinium-based MRI contrast agent (58-59).
Starpharma, in collaboration with its US-based wholly owned company Dendritic Nanotechnologies (Mount Pleasant, MI), recently
announced the commercial launch of its Priostar dendrimer-based technology research product called the NanoJuice Transfection
Kit in addition to the Starburst- and Priostar-based dendrimer family (60). Because of the presence of large numbers of functional
groups, these highly branched dendrimers are capable of binding to DNA. They will be useful for transfection of DNA into the
variety of difficult-to-transfect cells (61). As the number of commercial applications of dendrimer technology increases,
acceptance and confidence in this novel technology will gain strength for use in future products.
Scientists have explored the use of dendrimers for various applications in topical and cosmetic product development. Use of
dendrimers in commercial pharmaceutical and cosmetic products will largely be driven by mitigating risk factors such as cost,
large-scale availability, safety concerns, and regulatory issues. Although no pharmaceutical or cosmetic products containing
dendrimers are currently on the market, dendrimer technology holds great potential to add value to pharmaceutical or cosmetic
products. Use of dendrimers as topical microbicide products is marching ahead with positive results and, in the process, leading
the field for HIV prevention. The authors expect that dendrimer technology will find increasing applications in commercial
products of all types in coming years.
The authors would like to thank Ross Durland, PhD, director of product development at AM Biotechnologies LLC (Galveston, TX)
for providing valuable input for this article.
Gaurav T. Tolia*, MS, PMP, is a senior scientist and group leader of formulations with Altea Therapeutics, 387 Technology Circle NW, Suite
100, Atlanta, GA 30093, tel. 404.835.6340, fax 404.835.6450, firstname.lastname@example.org
. Hannah H. Choi, PhD, is a principal scientist with GlaxoSmithKline.
*To whom all correspondence should be addressed.
Submitted: June 23, 2008; Accepted: Aug. 3, 2008.