Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration

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Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration. / Zou, Jing; Feng, Hao; Sood, Rohit; Kinnunen, Paavo K.J.; Pyykko, Ilmari.

In: Nanoscale Research Letters, Vol. 12, 372, 2017, p. 1-14.

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Zou, Jing ; Feng, Hao ; Sood, Rohit ; Kinnunen, Paavo K.J. ; Pyykko, Ilmari. / Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration. In: Nanoscale Research Letters. 2017 ; Vol. 12. pp. 1-14.

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@article{6c69965dfe57458bbcc13fb10a0810ab,
title = "Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration",
abstract = "Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3′OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.",
keywords = "Animal, Biological Response, Drug Delivery, Inner Ear, Liposome, Nanomaterial",
author = "Jing Zou and Hao Feng and Rohit Sood and Kinnunen, {Paavo K.J.} and Ilmari Pyykko",
year = "2017",
doi = "10.1186/s11671-017-2142-5",
language = "English",
volume = "12",
pages = "1--14",
journal = "Nanoscale Research Letters",
issn = "1931-7573",

}

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TY - JOUR

T1 - Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration

AU - Zou, Jing

AU - Feng, Hao

AU - Sood, Rohit

AU - Kinnunen, Paavo K.J.

AU - Pyykko, Ilmari

PY - 2017

Y1 - 2017

N2 - Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3′OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.

AB - Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3′OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.

KW - Animal

KW - Biological Response

KW - Drug Delivery

KW - Inner Ear

KW - Liposome

KW - Nanomaterial

UR - http://www.scopus.com/inward/record.url?scp=85019764244&partnerID=8YFLogxK

U2 - 10.1186/s11671-017-2142-5

DO - 10.1186/s11671-017-2142-5

M3 - Article

VL - 12

SP - 1

EP - 14

JO - Nanoscale Research Letters

JF - Nanoscale Research Letters

SN - 1931-7573

M1 - 372

ER -

ID: 13680918