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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Covalent Poly(lactic acid) Nanoparticles for the Sustained Delivery of Naloxone
ACS applied bio materials, v 2(8), pp 3418-3428
19 Aug 2019
PMID: 31497753
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The opioid epidemic currently plaguing the United States has been exacerbated by an alarming rise in fatal overdoses as a result of the proliferated abuse of synthetic mu opioid receptor (MOR) agonists, such as fentanyl and its related analogues. Attempts to manage this crisis have focused primarily on widespread distribution of the clinically approved opioid reversal agent naloxone (Narcan); however, due to the intrinsic metabolic lability of naloxone, these measures have demonstrated limited effectiveness against synthetic opioid toxicity. This work reports a novel polymer-based strategy to create a long-acting formulation of naloxone with the potential to address this critical issue by utilizing covalent nanoparticle (cNP) drug delivery technology. Covalently loaded naloxone nanoparticles (Nal-cNPs) were prepared via the naloxone-initiated, ring-opening polymerization (ROP) of l-lactide in the presence of a bifunctional thiourea organocatalyst with subsequent precipitation of the resulting naloxone–poly(l-lactic acid) polymer. This protocol afforded well-defined nanoparticles possessing a drug loading of approximately 7% w/w. The resulting Nal-cNPs demonstrated excellent biocompatibility, while exhibiting sustained linear release kinetics in vitro and blocking the effects of high dose (10 mg/kg) acute morphine for up to 98 h in an in vivo rodent model of neuropathic pain.
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Details
- Title
- Covalent Poly(lactic acid) Nanoparticles for the Sustained Delivery of Naloxone
- Creators
- Andrew J Kassick - Allegheny General HospitalHeather N Allen - Duquesne UniversitySaigopalakrishna S Yerneni - Carnegie Mellon UniversityFathima Pary - Oklahoma State UniversityMarina Kovaliov - Allegheny General HospitalCooper Cheng - Allegheny General HospitalMarco Pravetoni - University of MinnesotaNestor D Tomycz - Allegheny General HospitalDonald M Whiting - Allegheny General HospitalToby L Nelson - Oklahoma State UniversityMichael Feasel - United States Army Combat Capabilities Development CommandPhil G Campbell - Carnegie Mellon UniversityBenedict Kolber - Duquesne UniversitySaadyah Averick - Allegheny General Hospital
- Publication Details
- ACS applied bio materials, v 2(8), pp 3418-3428
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- SOM Dean - Research Administration; Neurosurgery
- Web of Science ID
- WOS:000616371100030
- Scopus ID
- 2-s2.0-85070820892
- Other Identifier
- 991021448063604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Materials Science, Biomaterials
- Nanoscience & Nanotechnology