Table 1.

Main nano-drug delivery systems for IVDD.

Category	Size	Removal manner	Scalability	Advantages	Disadvantages	Refs.
Liposome	50 nm −5 μm	Biodegradation	High	•High biocompatibility	•Low encapsulation rate	[92,95]
				•Encapsulates drugs of different properties	•Low reproducibility
				•Less immunogenic	•Easily degraded
PNPs	1–1000 nm	Biodegradation	Medium	•Higher encapsulation rate	•Cumbersome and unstable synthesis process	[186,192]
				•Good biocompatibility and biodegradability
				•Low toxicity
Inorganic nanoparticles	1–100 nm	Cell internalization or foreign body reaction	Medium	•Good biocompatibility and stability	•Low solubility	[187,188]
					•Toxicity
					•Low clearance rate
Polymer micelles	Vared	Biodegradation	High	•Increased drug solubility	•Particle aggregation	[193]
				•Improved drug bioavailability
				•High structural stability
Nanofibers	Varied	Cell internalization or foreign body reaction	Medium	•Prolonged drug release •Improved drug stability	•Low reproducibility	[194,195]
Nano-hydrogels	Mesh size of 5–100 nm	Biodegradation	High	•Good biocompatibility •Restore the height of intervertebral space	•Irreversibly entrap the drug	[196,197]
					•Potential toxicity
					•Not suitable for hydrophilic drugs
					•Decreased adhesiveness