Polymer nanocarriers protecting active enzyme cargo against proteolysis

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

doi:10.1016/j.jconrel.2004.10.017

Polymer nanocarriers protecting active enzyme cargo against proteolysis

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

Chemical and Materials Engineering

Research output: Contribution to journal › Article › peer-review

93 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 language	English
Pages (from-to)	427-439
Number of pages	13
Journal	Journal of Controlled Release
Volume	102
Issue number	2
DOIs	https://doi.org/10.1016/j.jconrel.2004.10.017
State	Published - 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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10.1016/j.jconrel.2004.10.017

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title = "Polymer nanocarriers protecting active enzyme cargo against proteolysis",

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.",

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author = "Dziubla, {Thomas D.} and Adnan Karim and Muzykantov, {Vladimir R.}",

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).",

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N2 - 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.

AB - 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.

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Polymer nanocarriers protecting active enzyme cargo against proteolysis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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