Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application

Michael R. Arul, Changli Zhang, Ibtihal Alahmadi, Isaac L. Moss, Yeshavanth Kumar Banasavadi-Siddegowda, Sama Abdulmalik, Svenja Illien-Junger, Sangamesh G. Kumbar

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Article number52
JournalJournal of Functional Biomaterials
Volume14
Issue number2
DOIs
StatePublished - Feb 2023
Externally publishedYes

Keywords

  • cellulose
  • drug delivery
  • fluorescent nanoparticles
  • injectable
  • intervertebral disc
  • polycaprolactone

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