Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear

Surovtseva, Elena V.; Johnston, A. H.; Zhang, Weikai; Zhang, Ya; Kim, Adele; Murakoshi, Michio; Wada, Hiroshi; Newman, Tracey A.; Zou, Jing; Pyykkö, Ilmari

doi:10.1016/j.ijpharm.2011.12.042

Cited by 45 publications

(26 citation statements)

References 22 publications

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“…Prestin is an electromotility protein that is solely expressed on the surface of outer hair cells (OHCs) [71]. Discovery of prestin as an outer hair cell (OHC) biomarker paved the way for targeted OHC drug delivery.…”

Section: Applications Of Nanotechnology To Sensorineural Hearing Lmentioning

confidence: 99%

Advances in nano-based inner ear delivery systems for the treatment of sensorineural hearing loss

Chao

Brant

et al. 2017

Advanced Drug Delivery Reviews

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Sensorineural hearing loss (SNHL) is one of the most common diseases, accounting for about 90% of all hearing loss. Leading causes of SNHL include advanced age, ototoxic medications, noise exposure, inherited and autoimmune disorders. Most of SNHL is irreversible and managed with hearing aids or cochlear implants. Although there is increased understanding of the molecular pathophysiology of SNHL, biologic treatment options are limited due to lack of noninvasive targeted delivery systems. Obstacles of targeted inner ear delivery include anatomic inaccessibility, biotherapeutic instability, and nonspecific delivery. Advances in nanotechnology may provide a solution to these barriers. Nanoparticles can stabilize and carry biomaterials across the round window membrane into the inner ear, and ligand bioconjugation onto nanoparticle surfaces allows for specific targeting. A newer technology, nanohydrogel, may offer noninvasive and sustained biotherapeutic delivery into specific inner ear cells. Nanohydrogel may be used for inner ear dialysis, a potential treatment for ototoxicity-induced SNHL.

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Section: Applications Of Nanotechnology To Sensorineural Hearing Lmentioning

confidence: 99%

Advances in nano-based inner ear delivery systems for the treatment of sensorineural hearing loss

Chao

Brant

et al. 2017

Advanced Drug Delivery Reviews

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“…In recent research, two 12-mer peptides (A665 and A666) with affinity to prestin were identified, and polymersomes covalently labeled with these peptides demonstrated effective targeting to outer hair cells in a rat cochlear explant study (Surovtseva et al, 2012). In another study using nanoparticles conjugated with a neurotrophin-derived peptide ligand, specific targeting of nanoparticles to spiral ganglion neurons, Schwann cells, and nerve fibers was shown (Roy et al, 2010).…”

Section: Number Of Particles In Lateral Wall Modiolusmentioning

confidence: 99%

Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles

Kim

Park

et al. 2014

Drug Delivery

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(2015) Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles, Drug Delivery, 22:3, 367-374, DOI: 10.3109/10717544.2013 Objective: To evaluate the permeability and safety of a drug delivery system for the inner ear using a poly(2-hydroxyethyl aspartamide) (PHEA) polymersome. Materials and 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.

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“…For example, polymersome surface functionalized with hNgf EE peptide (a nerve growth factor-derived ligand) shows great potential for specific targeting to spiral ganglion neurons, 33 while engineered the polymersomes with prestin-binding peptides can promote their targeting to the OHCs. 5 In our study, the PLGA-based NPs modified with hydrophilic molecules delivered their cargo to the OHCs more effectively than unmodified NPs did, indicating that hydrophilic molecules could also play the role of ligands for entry to OHC.…”

mentioning

confidence: 48%

“…[2][3][4] To improve the efficiency for treating hearing loss associated with OHC pathology, targeted drug delivery to OHCs in the organ of Corti (OC) of cochlea is required. 5,6 Novel nanosized drug vehicles are thought to overcome the limitations of classic approaches through controlled or sustained release into the inner ear fluids, cellular cytoplasm, or the nucleus of targeted cells. 7,8 Therefore, drugs have been delivered to the inner ear based on nanomedicine strategies using different types of nanocarriers.…”

Section: Introductionmentioning

confidence: 99%

“…10 More interestingly, it has been illustrated in our previous study that Since the NP surface contacts with biological systems, their characteristics greatly impact NP performance in vivo and the overall effectiveness. 5,12,13 Changing the surface chemistry of the engineered NPs with biocompatible hydrophilic polymers or copolymers increases the circulation time and delays the removal of NPs by the mononuclear phagocyte system, which prevents rapid clearance before reaching the targeted tissues and delivering drugs. 12,14,15 Based on these background studies, we theorized that attachment of these hydrophilic molecules onto the NP surface would enhance nanocarrier delivery to OHCs in the cochlea.…”

Section: Introductionmentioning

confidence: 99%

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Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

Wen¹,

Ding²,

Cai³

et al. 2016

IJN

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Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear

Cited by 45 publications

References 22 publications

Advances in nano-based inner ear delivery systems for the treatment of sensorineural hearing loss

Advances in nano-based inner ear delivery systems for the treatment of sensorineural hearing loss

Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles

Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

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