Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles.
BACKGROUND
Local delivery systems for treatment of intractable inner ear disorders have been attempted by many investigators.


OBJECTIVE
To evaluate the permeability and safety of a drug delivery system for the inner ear using a poly(2-hydroxyethyl aspartamide) (PHEA) polymersome.


METHODS
One-month-old male C57/BL6 mice were used. We administered the same amount of the fluorescent dye, Nile red, into the middle ear in two forms: loaded in PHEA polymersomes (NP group) or diluted in ethanol (NR group). At 1 day after administration, we harvested the cochlea and counted visible red particles in the tissues of cochlea under confocal microscopy and compared the groups. In a safety evaluation, 1 week after the same surgery, we conducted hearing tests and histological evaluations of the bulla and cochlea, and compared the results with those of the sham operation and negative control groups.


RESULTS
In terms of permeability, the number of red particles in the organ of Corti was increased significantly in the NP group, and three subjects in the NP group showed uptake of red particles in inner hair cells. However, there was no statistically significant difference in the observations in the lateral wall or modiolus. In safety tests, the NP and sham-operation groups showed decreased DPOAE responses and mildly swollen middle ear mucosa, compared with the negative control group, which was thought to be the result of postoperative changes.


CONCLUSIONS
PHEA nanoparticles may have utility as a drug carrier into the inner ear in terms of both permeability and safety.
Department of Otolaryngology-Head & Neck Surgery, The Catholic University of Korea, College of Medicine , Seoul , Republic of Korea .
Dong-Kee
DK
Kim
Shi-Nae
SN
Park
Kyoung-Ho
KH
Park
Chan Woo
CW
Park
Keum-Jin
KJ
Yang
Jong-Duk
JD
Kim
Min-Sik
MS
Kim
D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism*; D006320:Hearing Tests; D008297:Male; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D010539:Permeability; D014018:Tissue Distribution
D004337:Drug Carriers; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide)
Confocal microscopy; drug delivery; hearing loss; inner ear; polymersome