title: Filamentous polymer nanocarriers of tunable stiffness that encapsulate the therapeutic enzyme catalase.
abstract: Therapeutic proteins are prone to inactivation by aggregation, proteases and natural inhibitors, motivating development of protective delivery systems. Here we focus on protective encapsulation of the potent antioxidant enzyme, catalase, by filamentous polymer nanocarriers (f-PNC), with the specific goal of addressing whether polymer molecular weight (MW) controls formation and structural properties such as size and stiffness. While maintaining the same MW ratio of polyethylene glycol to polylactic acid, a series of PEG-b-PLA diblock copolymers were synthesized, with total MW ranging from about 10 kg/mol to 100 kg/mol. All diblocks formed f-PNC upon processing, which encapsulated active enzyme that proved resistant to protease degradation. Further, f-PNC stiffness, length, and thickness increased with increasing MW. Interestingly, heating above a polymer's glass transition temperature (<30 degrees C) increased f-PNC flexibility. Thus, we report here for the first time f-PNC that encapsulate an active enzyme with polymer MW-tunable flexibility, offering several potential therapeutic applications.
authors.affiliation: Department of Bioengineering, Institute for Translational Medicine and Therapeutics, and Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Simone
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
mesh_terms: D055162:Biocatalysis; D004337:Drug Carriers; D004798:Enzymes / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013696:Temperature
chemical_list: D004337:Drug Carriers; D004798:Enzymes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)