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A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
Micelles for delivery of nitric oxide
Yun Suk Jo1, André J van der Vlies, Jay Gantz
1Institute of Bioengineering (IBI), Ecole Polytechnique Federale de Lausanne, Lausanne CH 1015, Switzerland.
Journal of the American Chemical Society
|September 22, 2009
Summary
New block copolymers deliver nitric oxide (NO) for 7 days via self-assembling micelles. This breakthrough enables long-term NO therapy, targeting complex tissues like arteries for enhanced treatment.
Area of Science:
- Polymer Chemistry
- Biomaterials Science
- Drug Delivery Systems
Background:
- Nitric oxide (NO) has therapeutic potential but suffers from short half-life and instability.
- Developing stable NO-releasing systems is crucial for effective long-term NO-based therapies.
- Block copolymers offer a versatile platform for controlled release applications.
Purpose of the Study:
- To design and synthesize novel block copolymers for sustained nitric oxide (NO) release.
- To investigate the self-assembly behavior of these copolymers into micelles for NO encapsulation.
- To evaluate the long-term NO release kinetics and tissue penetration capabilities of the developed system.
Main Methods:
- Synthesis of a block copolymer comprising hydrophilic N-acryloylmorpholine (AM) and a hydrophilic precursor N-acryloyl-2,5-dimethylpiperazine (AZd).
- Chemical modification of the AZd block to form N-diazeniumdiolate (NONOate) for NO generation, inducing hydrophobicity.
- Characterization of micelle formation, NO release kinetics, and tissue penetration using techniques like dynamic light scattering and in vitro release studies.
Main Results:
- Successful synthesis of AM-AZd block copolymers that form ca. 50 nm spherical micelles upon NONOate formation.
- Demonstrated a remarkable 7-day half-life for NO release due to micellar core shielding of the NONOate.
- Released NO regenerated the original soluble polymer, indicating a recyclable system.
- NO-loaded micelles showed ability to penetrate complex biological tissues, such as arterial media.
Conclusions:
- Block copolymer pro-amphiphiles and amphiphiles provide a robust platform for very long-term nitric oxide (NO) delivery.
- The self-micellization triggered by NO-generating groups offers a unique mechanism for controlled release and enhanced stability.
- These NO-releasing micelles show promise for advanced NO-based therapies targeting challenging biological environments.
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