Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application

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.

Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy

“…To determine the particle size of the liposome nanoparticles, dynamic light scattering method was used. 77 In this method, 0.1 wt% of the nanoparticle solution was dispersed in ultra-filtered DI water at 25 °C and subjected to a laser beam with a wavelength of 632.6 nm. The scattering pattern of each formulation was then recorded to measure the particle size.…”

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives

“…Furthermore, this approach holds promise for treating other types of degenerative diseases associated with cellular senescence. In a study conducted by Arul et al, 92 they developed nanoparticles using cellulose acetate and polycaprolactone-polyethylene glycol. These nanoparticles were conjugated with a novel fluorescent dye called 1-oxo-1H-pyrido [2,1-b] [1,3] benzoxazole-3-carboxylic acid (PBC) using an oil-in-water emulsion technique.…”

“… Lim et al 91 2022 Polymeric nanoparticles ABT263 Rats In situ injection Eliminated senescent cells, reduced pro-inflammatory cytokines and matrix proteases. Arul et al 92 2023 Polymeric nanoparticles Indomethacin, aminopyridine Mice In situ injection Nanoparticles remained within disc. Yu et al 94 2022 Nanofibers Fucoidan Rats In situ implantation Reduced the expression of COX-2 and deposited more ECM between the scaffold layers.…”

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

“…With the rapid developments of nanomedicine, many biological delivery systems have been investigated for transferring miRNAs to treat IDD, including organic (polymeric or lipidic) nanoparticles [ 18 – 22 ], inorganic nanoparticles [ 23 , 24 ], nano-hydrogels [ 25 – 27 ], and extracellular vesicles (EVs) [ 28 – 30 ]. Different delivery systems possess different biological and release characteristics, and therefore hold promise for advancing the treatment of IDD [ 17 , 31 ].…”

“…In addition to EVs, polymeric nanoparticles have emerged as an attractive nanodrug vehicle, offering superior control over their structure, mechanical properties, and composition. Polymeric nanoparticles are easier to chemically modify, can be customized for specific applications, and can be manufactured on a large scale to provide renewable possibilities [ 18 ]. In our preclinical animal models of osteoarthritis [ 12 , 13 ], polymeric nanoparticles combined with aptamer conjugates could enhance intracellular uptake, reduce cellular apoptosis and increase extracellular matrix (ECM) production.…”