LAUSR

8-Arm star polypep(o)ides comprising cationic polylysine and hydrophilic polysarcosine blocks with a degree of polymerization of 30 per block are synthesized. Two different block sequences with polylysine as the inner and polysarcosine as the outer block and vice versa are obtained in addition to a statistical copolymer. Analysis of the enzymatic hydrolysis by the proteolytic enzyme trypsin demonstrates a strong dependance on structural arrangements. While polypept(o)ide disintegration is detectible after 24 hours by Size Exclusion Chromatography (SEC), significant hydrolysis of the lysine blocks is only monitored after 48 hours by fluorescamine labeling of the produced lysine and clearly accelerated in structures with more accessible polylysine blocks. All structures are capable of complexing plasmid DNA and form gene nanomedicines at sizes around or below 200 nm as determined by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and Transition Electron Microscopy (TEM). The polyplex formation is slightly enhance for both block structures over the random copolypept(o)ide. Moreover, it is demonstrated that the polyplexes can transport through mucus. The results highlight the importance of structural control in compartmentalized polymeric gene vector candidates with hydrophilic domains for potential mucosal delivery. This article is protected by copyright. All rights reserved.