Table 1.

Drug delivery systems in NIHL animal models

Drug delivery systems	Characteristics	Drug	Pharmacological action	Animals	Noise	Administration	Therapeutic outcomes	Ref.
PEGylated PLA nanoparticles	116 nm	Betamethasone phosphate	Anti-inflammatory	CBA/N mice4-6 weeks	OBN 120 dB SPL 8 kHz 2 h	IVImmediately after noise	GR translocation into the nuclei in OHCs↓ABR TS at 8 kHz on day 14, 32 kHz on days 7 and 14↓OHC loss in the apical turns; ↓IHC loss in the apical and basal turns	131
Solid lipid nanoparticles	Not described	Edaravone	Antioxidant	Guinea pigsAdult	SN 110 dB SPL 0.25-4 kHz 2 h/d, 4 d	ITI1 d after noise	↓ABR TS on day 4↓ROS in cochlea	161
Zeolitic imidazolate framework-based nanoparticles	105 nm PDI = 0.22 Zeta potential = -6.9 mV	Methylprednisolone	Anti-inflammatory	C57BL/6J mice4-5 weeks	WN 100 dB SPL 3 h/d, 3 d	IVBefore noise	↓ABR TS at 16 kHz, 24 kHz, and 32 kHz↓HC loss at basal and middle turns	130
Solid lipid nanoparticles	203 nmPDI=0.361	Clozapine	Antioxidant	Guinea pigsAdult	SN 110 dB SPL 0.25 - 4 kHz 2 h/d, 4 d	ITIImmediately after noise	↓ABR TS on day 6↓ROS in cochlea	162
Cross-linked hyaluronic acid with polylactide-co-glycolide microcapsules	50 μm	Dexamethasone;Insulin-like growth factor 1	Anti-inflammatory;Anti-apoptosis; Inducing the proliferation of supporting cells	SD Rats6 weeks	WN 3.7 h	ITI 3 h after noise	↓ABR TS	163
ROS-responsive and OHC-targeting liposomes	219.08 ± 8.86 nmZeta potential = -6.70 ± 0.13 mV	Poly(propylenesulfide)120;Berberine	Anti-inflammatory and antioxidant	Guinea pigs10-12 weeks	WN 120 dB SPL 6.3-20 kHz 4 h	RWM application 12 h after noise	↓MDA and ↑SOD ↓TNF-α, IL-6 and IL-1↓OHC loss in four turns and better morphology of OHCs↓ABR TS at 8, 16 and 24 kHz on days 4, 7 and 14	164
OHC-targeting liposomes	116.6 nmzeta potential = - 18.58 mV	forskolin	Antioxidant	C57BL/6J mice	WN 115 dB SPL 2-20 kHz 2 h	RWM application3 d before noise	↓ABR TS at 4, 8 and 16 kHz on days 1, 7 and 14; 32 kHz on day 28↓OHC loss in the mid-basal turns	165
Superparamagnetic iron oxide nanoparticles	magnetically driven	AAV2-BDNF vectors	Promoting the SGNs survival	Long-Evans rats6 - 8 weeks	OBN110 dB SPL8-16 kHz 2 h	RWM applicationMagnet placed on the contralateral ear for 30 min3 d after noise	↓ABR TS at 16, 24 and 32 kHz by 2 weeks↓Decrease of ABR wave I amplitude↓Synaptic ribbon loss in the basal and mid turns ↑BDNF expression	166
Gelatin methacryloyl microgel particles	32.81 μmCoefficient of variation = 15%	Dexamethasone sodium phosphate	Anti-inflammatory	Guinea pigsAdult	WN 120 dB SPL 6 h	ITI1 d before noise	↓ABR TS at 4, 16, 24, 32 kHz↓OHC loss↓Synaptic ribbon loss↓Decrease of ABR wave I amplitude↓Increase of ABR wave I latency	143
Gelatin hydrogel	Biodegradable	Insulin-like growth factor 1	Anti-apoptosis; Inducing the proliferation of supporting cells	Guinea pigsAdult	OBN 120 dB SPL 4 kHz 5 h	RWM application 5 h after noise	↓ABR TS at 4 kHz on days 14 and 21; 8 kHz on day 14↓OHC loss in basal and middle turns	167
Gelatin hydrogel	Biodegradable	Hepatocyte growth factor	Anti-apoptosis	Guinea pigs4 weeks	OBN 120 dB SPL 4 kHz 3 h	RWM application 1 h after noise	↓ABR TS at 16 kHz on day 21↓OHC loss in the 60-80% distance from the apex	168
Chitosan glycerophosphate hydrogel containing PEGylated OHC-targeting liposomes	Liposomes: OHCs targeting 87 ± 5 nmGel: Chitosan glycerophosphate-based Thermosensitive	D-JNKi-1	Anti-apoptosis	CBA/J mice6-10 weeks	WN 115-120 dB SPL 6.3-20 kHz 4 h	RWM application 2 d before noise	↓ABR TS in 4, 8, 16, 24, 32 kHz in 1-14 days	105
Hyaluronic acid gel containing liposomes	Liposomes: 140 nmGel: Hyaluronic acid-based	Dexamethasone	Anti-inflammatory	Guinea pigs	PT 100 dB SPL 5 kHz 1 h	RWM application 2 d after noise	No additional hearing recovery at 4, 16, 24 and 32 kHz compared to spontaneous recovery	169
Thermosensative hydrogel containing sodium phosphate multivesicular liposomes	Liposomes: 14.7 μmGel: Poloxamer-based; Gelling temperature at 34.9 °C	Dexamethasone	Anti-inflammatory	Guinea pigs Adult	WN 112 dB SPL 20-20000 Hz 6 h	ITI1 d before noise	↓ABR TS at 4, 8, 16 and 24 kHz on day 7↓OHC loss in the basal and middle turns	170
Monodisperse droplets of water	6.96 μmFlow rate = 20 μL/min	Methylprednisolone	Anti-inflammatory	Guinea pigsAdult	WN 106 dB SPL 15-125 kHz 48 h	ITIImmediately after noise	↓ABR TS after 2 weeks↓OHC loss in 5 and 8 kHz frequency range	171
Ultrasound-aided microbubbles	7.09 μm10^8 bubbles/mL	Dexamethasone	Anti-inflammatory	Guinea pigs	WN 118 dB SLP 5 h	RWM application followed by ultrasound2 h before noise	↓ABR TS at 8, 16, and 32 kHz on days 7, 14, and 28↓OHC loss in the basal and second turns↓HMGB1 and ICAM-1 expression in spiral ligament	71
Ultrasound-aided microbubbles	0.7-10 μm 1-5 × 105 bubbles/mL	Insulin-like growth factor 1	Anti-apoptosis; Inducing the proliferation of supporting cells	Guinea pigs	NBN 118 dB SPL 8 kHz 5 h	RWM application or ITI followed by ultrasound 24 h after noise	↓ABR TS at 8, 16 and 24 kHz on days 14 and 28; 32 kHz on day 28↓OHC loss in the basal and second turns ↓Synaptic ribbon loss in the basal and second turns ↑Akt1 and Mapk3 expression	172

Abbreviations: ABR: auditory brainstem response; AN: after noise; BN: before noise; GR: glucocorticoid receptor; HC: hair cell; HGF: hepatocyte growth factor; HMGB1: high mobility group box 1; ICAM-1: intercellular adhesion molecule-; IHC: inner hair cell; IL-1: interleukin 1; IL-6: interleukin 6; IP: intraperitoneal; IT: intratympanic; IV: intravenous; MDA: malondialdehyde; NBN: narrowband noise; NP: nanoparticle; OBN: octave band noise; OHC: outer hair cell; PDI: polydispersity index; PEG: polyethylene glycol-coated; PLA: polylactic acid; PT: pure tone; rhIGF-1: recombinant human insulin-like growth factor 1; ROS: reactive oxygen species; RWM: round window membrane; SN: stationary noise; SPL: sound pressure level; SOD: superoxide dismutase; TNF-α: tumor necrosis factor; TS: threshold shift; WN: white noise