Polymer nanocarriers protecting active enzyme cargo against proteolysis

Thomas D. Dziubla, Adnan Karim, Vladimir R. Muzykantov

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

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 ∼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 2O 2, was freely diffusible in the PNC polymer. Furthermore, PNC-loaded catalase stably retained 25-30% of H 2O 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.

Original languageEnglish
Pages (from-to)427-439
Number of pages13
JournalJournal of Controlled Release
Volume102
Issue number2
DOIs
StatePublished - Feb 2 2005

Bibliographical note

Funding Information:
The authors would like to thank Anthony Lowman and his laboratory in the Department of Chemical Engineering at Drexel University for the generous use of their FTIR and helpful comments in drafting this work. Thanks are also given to Vladimir Shuvaev for advice in determination of catalase enzymatic activity. Furthermore, thanks are given to Karen Winey and her laboratory in the Materials Science and Engineering Department at the University of Pennsylvania providing use to their GPC. Finally, Fariyal Ahmed in the laboratory of Dennis Discher in the department of chemical engineering at the University of Pennsylvania is graciously acknowledged for reviewing this manuscript. Personal assistance was provided by an NIH NRSA postdoctoral training grant. This work was funded by a grant from the National Institute of Health (NIH RO1 HL078785).

Keywords

  • Antioxidant delivery
  • Biodegradable
  • Catalase
  • Nanoparticle
  • Protein loading

ASJC Scopus subject areas

  • Pharmaceutical Science

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