Abstract: The invention provides sequential poly(ester amide)s derived from Proline and that are synthesized by a two-step method, involving a final thermal polyesterification reaction. Molecular weights of polymers prepared by this method are from 14,000 Da to about 77,000 Da.1 When invention proline-based PEAs were thermally characterized, their glass transition temperatures were lower than other alpha-amino acid based poly(ester amides) due to lack of internal hydrogen bonding. These Proline-based PEAs assemble as nano-particles in aqueous solutions and form complexes with various cations and biologies, including hydrophobic small molecule drugs and biologies. Therefore the invention Proline-based PEAs are useful for drug delivery applications requiring a polymer with a molecular weight in the range from 14,000 Da to about 77,000 Da and for fabrication of nanoparticles for delivery of hydrophobic drugs.