Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application

• Type of Material: Article
• Authors: Michael R Arul, University of Connecticut Health, Farmington; Changli Zhang, Emory University; Ibtihal Alahmadi, University of Connecticut, Storrs; Isaac L Moss, University of Connecticut Health, Farmington; Yeshavanth Kumar Banasavadi-Siddegowda, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda; Sama Abdulmalik, University of Connecticut Health, Farmington; Svenja Illien-Junger, Emory University; Sangamesh G Kumbar, University of Connecticut Health, Farmington
• Language: English
• Date: 2023-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/jfb14020052
• Title of Journal or Parent Work: JOURNAL OF FUNCTIONAL BIOMATERIALS
• Volume: 14
• Issue: 2
• Grant/Funding Information: National Institutes of Biomedical Imaging and Bioengineering of the National Institutes of Health (#R01EB020640, #R56NS122753 and # R01EB030060); U.S. Army Medical Research Acquisition Activity (USAMRAA), through the CDMRP Peer-Reviewed Medical Research Program under Award No.W81XWH2010321 and National Institute of Arthritis and Musculoskeletal and Skin Diseases (#R01AR078908).
• Keywords: Engineering, Biomedical; CONTROLLED-RELEASE; injectable; DEGENERATION; Science & Technology; CELLULAR UPTAKE; NETWORK; intervertebral disc; NUCLEUS PULPOSUS; drug delivery; cellulose; WATER-SOLUBLE DRUGS; Engineering; TASTE MASKING; DELIVERY; NANOPARTICLES; Materials Science, Biomaterials; fluorescent nanoparticles; REGENERATION; polycaprolactone; Materials Science; Technology
• Research Categories: Health Sciences, Medicine and Surgery

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.