Stealth-nanoparticle strategy for enhancing the efficacy of steroids in mice with noise-induced hearing loss.
OBJECTIVE
This study aimed to investigate the efficacy of encapsulating steroids, which is a primary choice for the treatment of sensorineural hearing loss, in polyethylene glycol-coated polylactic acid nanoparticles for drug delivery to the cochlea.


METHODS
We prepared polyethylene glycol-coated polylactic acid nanoparticles encapsulating rhodamine or betamethasone phosphate (BP), and administered them systemically to CBA/N mice previously exposed to intense noise. We assessed nanoparticle distribution using rhodamine fluorescence, BP concentrations in tissues, nuclear translocation of glucocorticoid receptors and the function and histology of the mouse cochleae.


CONCLUSIONS
Polyethylene glycol-coated polylactic acid nanoparticles delivered BP to cochleae over a sustained period, resulting in significant reductions in histological and functional damage to cochleae and indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of BP in acute sensorineural hearing loss.
Department of Otolaryngology, Head & Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, Kyoto 606-8507, Kyoto, Japan.
Rie T
RT
Horie
Tatsunori
T
Sakamoto
Takayuki
T
Nakagawa
Tsutomu
T
Ishihara
Megumu
M
Higaki
Juichi
J
Ito
D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D003051:Cochlea / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012235:Rhodamines / Q000008:administration & dosage / Q000378:metabolism; D013256:Steroids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D011091:Polyesters; D011108:Polymers; D011965:Receptors, Glucocorticoid; D012235:Rhodamines; D013256:Steroids; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone