STARBURST® and Priostar™ dendrimers for enhanced drug solubilization

COLL 105

Sonke Svenson, svenson@dnanotech.com, Abhay S. Chauhan, Lori A. Reyna, and Donald A. Tomalia. Dendritic NanoTechnologies, Inc, 2625 Denison Drive, Mount Pleasant, MI 48858
Many drug candidates and launched products suffer from low bioavailability due to poor water solubility. Encapsulation of these drugs into water-soluble carriers can improve their water solubility and bioavailability. Poly(amidoamine) PAMAM STARBURST® and Priostar™ dendrimers are core-shell nanostructures with precise architecture and low polydispersity, which are synthesized in a generation-by-generation fashion around a core unit, resulting in high level of control over size, branching points and surface functionality. The ability to tailor dendrimer properties to the needs of a drug makes them ideal carriers for drug encapsulation. The anti-cancer drug cisplatin and the non-steroidal anti-inflammatory drug indomethacin have been encapsulated into STARBURST® and Priostar™ dendrimers, and their encapsulation efficiency and release profiles have been studied. Cisplatin encapsulation was successful using dendrimers with carboxylate surface. Dendrimer generation and size of the core molecule had little effect on the encapsulation efficiency. Release profiles revealed a two-step process, small burst release followed by sustained release over hours. Indomethatcin encapsulation was successful in dendrimers with amino, hydroxy and carboxylate surfaces. The encapsulation efficiency increased with dendrimer size, while release was dependent on surface groups and dendrimer size. The water solubility of both drugs was enhanced by orders of magnitude. In addition, it has been demonstrated on several cell lines in vitro that encapsulation into dendrimers reduces drug cytotoxicity.
 

Advances in Nanomedicine
2:00 PM-5:30 PM, Sunday, 10 September 2006 Sir Francis Drake -- Monterey/Cypress Rooms, Oral

Division of Colloid & Surface Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006