Polymer nanocarriers protecting active enzyme cargo against proteolysis.
Polymeric nanocarriers (PNCs), proposed as an attractive vehicle for vascular drug delivery, remain an orphan technology for enzyme therapies due to poor loading and inactivation of protein cargoes. To unite enzyme delivery by PNC with a clinically relevant goal of containment of vascular oxidative stress, a novel freeze-thaw encapsulation strategy was designed and provides approximately 20% efficiency loading of an active large antioxidant enzyme, catalase, into PNC (200-300 nm) composed of biodegradable block copolymers poly(ethylene glycol)-b-poly(lactic-glycolic acid). Catalase's substrate, H(2)O(2), was freely diffusible in the PNC polymer. Furthermore, PNC-loaded catalase stably retained 25-30% of H(2)O(2)-degrading activity for at least 18 h in a proteolytic environment, while free catalase lost activity within 1 h. Delivery and protection of catalase from lysosomal degradation afforded by PNC nanotechnology may advance effectiveness and duration of treatment of diverse disease conditions associated with vascular oxidative stress.
Dziubla
Thomas D
TD
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, 1 John Morgan/6068, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. dziubla@mail.med.upenn.edu
Karim
Adnan
A
Muzykantov
Vladimir R
VR
D002374:Catalase / Q000008:administration & dosage; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D004798:Enzymes / Q000008:administration & dosage* / Q000378:metabolism; D005615:Freezing; D006861:Hydrogen Peroxide; D007202:Indicators and Reagents; D008863:Microspheres; D010316:Particle Size; D010447:Peptide Hydrolases / Q000378:metabolism; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D011108:Polymers
D004337:Drug Carriers; D004798:Enzymes; D007202:Indicators and Reagents; D011108:Polymers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D010447:Peptide Hydrolases