Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application
Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/14/2/52 |
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| author | Michael R. Arul Changli Zhang Ibtihal Alahmadi Isaac L. Moss Yeshavanth Kumar Banasavadi-Siddegowda Sama Abdulmalik Svenja Illien-Junger Sangamesh G. Kumbar |
| author_facet | Michael R. Arul Changli Zhang Ibtihal Alahmadi Isaac L. Moss Yeshavanth Kumar Banasavadi-Siddegowda Sama Abdulmalik Svenja Illien-Junger Sangamesh G. Kumbar |
| author_sort | Michael R. Arul |
| collection | DOAJ |
| description | Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150–162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections. |
| first_indexed | 2024-03-11T08:37:00Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-11T08:37:00Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-285df28540ca447db6851714ab2eec842023-11-16T21:24:00ZengMDPI AGJournal of Functional Biomaterials2079-49832023-01-011425210.3390/jfb14020052Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc ApplicationMichael R. Arul0Changli Zhang1Ibtihal Alahmadi2Isaac L. Moss3Yeshavanth Kumar Banasavadi-Siddegowda4Sama Abdulmalik5Svenja Illien-Junger6Sangamesh G. Kumbar7Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USADepartment of Orthopedic Surgery, Emory University, Atlanta, GA 30308, USADepartment of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USADepartment of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USASurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USADepartment of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USADepartment of Orthopedic Surgery, Emory University, Atlanta, GA 30308, USADepartment of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USADamage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150–162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections.https://www.mdpi.com/2079-4983/14/2/52fluorescent nanoparticlesdrug deliveryinjectableintervertebral disccellulosepolycaprolactone |
| spellingShingle | Michael R. Arul Changli Zhang Ibtihal Alahmadi Isaac L. Moss Yeshavanth Kumar Banasavadi-Siddegowda Sama Abdulmalik Svenja Illien-Junger Sangamesh G. Kumbar Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application Journal of Functional Biomaterials fluorescent nanoparticles drug delivery injectable intervertebral disc cellulose polycaprolactone |
| title | Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application |
| title_full | Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application |
| title_fullStr | Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application |
| title_full_unstemmed | Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application |
| title_short | Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application |
| title_sort | novel injectable fluorescent polymeric nanocarriers for intervertebral disc application |
| topic | fluorescent nanoparticles drug delivery injectable intervertebral disc cellulose polycaprolactone |
| url | https://www.mdpi.com/2079-4983/14/2/52 |
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