title: Polypeptoid-block-polypeptide copolymers: synthesis, characterization, and application of amphiphilic block Copolypept(o)ides in drug formulations and miniemulsion techniques.
abstract: We report the synthesis of polysarcosine-block-polyglutamic acid benzylester (PSar-block-PGlu(OBn)) and polysarcosine-block-polylysine-ε-N-benzyloxycarbonyl (PSar-block-PLys(Z)) copolymers. The novel polypeptoid-block-polypeptide copolymers (Copolypept(o)ides) have been synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). Polymerization conditions were optimized regarding protecting groups, block sequence and length. While the degree of polymerization of the PSar block length was set to be around 200 or 400, PGlu(OBn) and PLys(Z) block lengths were varied between 20 to 75. The obtained block copolymers had a total degree of polymerization of 220-475 and dispersity indices between 1.1 and 1.2. Having ensured a nontoxic behavior up to a concentration of 3 mg/mL in HEK293 cells, the novel block copolymers have been applied to the synthesis of organic colloids (by miniemulsion polymerization and miniemulsion solvent evaporation process). Colloids of around 100 nm (miniemulsion polymerization) to 200 nm (miniemulsion process) have been prepared. Additionally, PSar-block-PGlu(OBn) copolymers have been used in a drug formulation of an adenylate cyclase inhibitor. Micelles of 28.0 nm (without drug) and 33.0 nm (with drug) diameter have been observed by fluorescence correlation spectroscopy (FCS). The polypeptoid-block-polypeptide formulation increased solubility of the drug and enhances its bioavailability, which leads to a reduction of intracellular cAMP levels in MaMel 91 melanoma cells.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Birke
authors.forename: David
authors.initials: D
authors.lastname: Huesmann
authors.forename: Annette
authors.initials: A
authors.lastname: Kelsch
authors.forename: Martin
authors.initials: M
authors.lastname: Weilbächer
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004655:Emulsions / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D034444:Peptoids / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004655:Emulsions; D010455:Peptides; D034444:Peptoids; D011108:Polymers; D013501:Surface-Active Agents