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 lackin...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2017-05-01
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| Series: | Nanoscale Research Letters |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s11671-017-2142-5 |
| _version_ | 1797713559215407104 |
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| author | Jing Zou Hao Feng Rohit Sood Paavo K. J. Kinnunen Ilmari Pyykko |
| author_facet | Jing Zou Hao Feng Rohit Sood Paavo K. J. Kinnunen Ilmari Pyykko |
| author_sort | Jing Zou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:38:19Z |
| format | Article |
| id | doaj.art-6ba091f065b5482e92f8443ba718e336 |
| institution | Directory Open Access Journal |
| issn | 1931-7573 1556-276X |
| language | English |
| last_indexed | 2024-03-12T07:38:19Z |
| publishDate | 2017-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nanoscale Research Letters |
| spelling | doaj.art-6ba091f065b5482e92f8443ba718e3362023-09-02T21:26:04ZengSpringerOpenNanoscale Research Letters1931-75731556-276X2017-05-0112111410.1186/s11671-017-2142-5Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic AdministrationJing Zou0Hao Feng1Rohit Sood2Paavo K. J. Kinnunen3Ilmari Pyykko4Department of Otolaryngology Head and Neck Surgery, Center for Otolaryngology-Head and Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical UniversityHearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of TampereHelsinki Biophysics and Biomembrane Group, Department of Biomedical Engineering and Computational Sciences, Aalto UniversityHelsinki Biophysics and Biomembrane Group, Department of Biomedical Engineering and Computational Sciences, Aalto UniversityHearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of TampereAbstract 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.http://link.springer.com/article/10.1186/s11671-017-2142-5NanomaterialLiposomeDrug DeliveryInner EarAnimalBiological Response |
| spellingShingle | Jing Zou Hao Feng Rohit Sood Paavo K. J. Kinnunen Ilmari Pyykko Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration Nanoscale Research Letters Nanomaterial Liposome Drug Delivery Inner Ear Animal Biological Response |
| title | Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration |
| title_full | Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration |
| title_fullStr | Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration |
| title_full_unstemmed | Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration |
| title_short | Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration |
| title_sort | biocompatibility of liposome nanocarriers in the rat inner ear after intratympanic administration |
| topic | Nanomaterial Liposome Drug Delivery Inner Ear Animal Biological Response |
| url | http://link.springer.com/article/10.1186/s11671-017-2142-5 |
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