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Development of PETAA Dendrimers: Better, Faster, Cleaner

Funded by MNIMBS Endowment

Key Investigators

Baohua Huang, Ph.D., Research Assistant Professor, Internal Medicine and MNIMBS

Polyamidoamine (PAMAM) dendrimers have unique attributes that have led to their use in a wide variety of biomedical applications. However, the complex synthesis of this polymer leads to variations in the structure and consistency of the final product, and makes scale-up of manufacturing difficult. This has limited the clinical translation of PAMAM-based materials.

MNIMBS’ Dr. Baohua Huang and colleagues have designed and synthesized novel Poly(EThyleneAmidoAmine) dendrimers through a rapid and highly efficient two-step method that employs an AB2 building block via a divergent approach. These synthesis methods overcame most of the disadvantages of PAMAM dendrimer production.

Figure 1: The structure of Generation 5 PETAA dendrimer. It has a less crowded interior than the PAMAM dendrimer but has a similar structure.

The advantages of this new PETAA dendrimer are: Firstly, no large excess of any regents was needed thus reducing the cost and purification time. Secondly, the process of one generation growth is about 1.5 weeks per generation versus 4 weeks per generation for PAMAM dendrimers. Thirdly, PETAA dendrimers have similar structures to PAMAM dendrimers and thus have similar physical properties; Fourthly, analytical data showed that PETAA dendrimers have lower polydispersities than PAMAM dendrimers. In addition, the structure of the PETAA dendrimers is more complete and more uniform than PAMAM dendrimers, especially at higher generations.

Figure 2: GPC elugram comparison of G5 PETAA and PAMAM dendrimers. This GPC comparison data shows the significant reduction in heterogeneity for the PETAA dendrimer as compared to the PAMAM dendrimer.

This unique synthetic process for PETAA dendrimers also offers the potential for large-scale production, therefore providing inherently more uniform and complete structures for exacting biomedical applications.

Technology Commercialization

MNIMBS is currently assessing the market demand for this new material technology.  The primary competitive advantage of the PETAA dendrimer compared to other available materials is expected to be a dramatic reduction in variations between synthesized lots.  This improved consistency will allow end users to achieve far greater reproducibility of post-market syntheses and functionalizations.  MNIMBS is assessing the scale-up requirements for the PETAA dendrimer and has initiated discussions with a major chemical distributor.  Patent protection is being pursued in the United States, European Union and Australia.

 

Publications

Baohua Huang, Shengzhuang Tang, Ankur Desai, Kyung-Hoon Lee, Pascale R. Leroueil, James R. Baker, Jr. ‘Novel Poly(EThyleneAmidoAmine) (PETAA) Dendrimers Produced Through a Unique and Highly Efficient Synthesis’. Polymer, 2011, 52 (26), 5975-5984.

 

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