Polyethylene glycol-polyamidoamine dendritic micelle as a matrix for substrate protection against alpha-chymotrypsin-catalyzed hydrolysis

COLL 301

Hu Yang and Stephanie T. Lopina. Department of Chemical Engineering and Biomedical Engineering, The University of Akron, Akron, OH 44325
Polyethylene glycol-polyamidoamine (PEG-PAMAM) unimolecular dendritic micelle could be used as a matrix to protect the encapsulated drug (peptides, etc.) from enzymatic degradation. However, the ratio of PEG/substrate needs to be quantified and optimized. A series of micelles were synthesized based on G2.5 or G3.0 Starburst PAMAM dendrimers, to which different amounts of PEG 2000 were attached. The rest of dendrimer surface sites of the G2.5 and G3.0 dendritic micelles were filled up by quinidine (alpha-chymotrypsin non-specific substrate) and N-succinyl-ala-ala-pro-phe-p-nitroanilide (Suc-AAPF-pNA, specific substrate), respectively. The synthesized complexes were characterized by MALDI-TOF MS, proton-NMR and FT-IR. The alpha-chymotrpsin-catalyzed hydrolysis of these complexes in PBS (pH=7.4) at room temperature were monitored by UV/Vis spectrometer in situ. The hydrolysis kinetics was studied to find an optimal PEG/substrate mole ratio to obtain good protection of substrate against enzyme degradation and high substrate-loading efficiency. The quantification and optimization of PEG-PAMAM dendritic micelle is further discussed.
 

Bio-Colloids
8:30 AM-10:30 AM, Tuesday, March 30, 2004 Marriott -- Orange County 3, Oral

Division of Colloid and Surface Chemistry

The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004