Charged polypeptide vesicles for intracellular drug delivery

PMSE 164

Timothy J. Deming, demingt@seas.ucla.edu1, Eric P. Holowka2, Victor Sun3, and Daniel T. Kamei, kamei@seas.ucla.edu3. (1) Departments of Bioengineering and Chemistry and Biochemistry, University of California, Los Angeles, 7523 Boelter Hall, Box 951600, Los Angeles, CA 90095-1600, (2) Materials Science & Engineering, University of California Santa Barbara, Engineering 2 Building, Room 1355, Santa Barbara, CA 93106-5050, (3) Department of Bioengineering/Biomedical Engineering, University of California, Los Angeles, 420 Westwood Plaza, 7523 Boelter Hall, Los Angeles, CA 90095-1600
Using transition metal catalysis chemistry for the polymerization of alpha-amino acid-N-carboxyanhydrides (NCAs), we have prepared amphiphilic diblock copolypeptides containing a variety of both hydrophilic and hydrophobic chains. The hydrophilic chains are composed of either cationic or anionic residues, and the hydrophobic chains are composed of natural non-polar amino acid residues such as leucine, valine and phenylalanine. By employing differernt amino acids, the chain conformations of individual domains can be altered. Ordered alpha-helical and beta-sheet segments can be prepared from enantiomerically pure amino acids, and disordered segments can be prepared using racemic amino acids. We report on the biomimetic self-assembly of a subset of block copolymers that form unilamellar vesicles with charged polypeptide coronas in aqueous solution. The processing methods and polymeric design features that control this self-assembly process will be discussed, and the role of the nature of the charged hydrophilic residues on interaction with epithelial and endothelial cells will be reported.