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

Abstract

(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.

A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

“…27 In addition, this reaction is widely used for conjugation of cysteinecontaining peptides and proteins. 28,29 In contrast, the binding of small peptides (such as A666 peptide, which is isolated from 3 rounds of sequential phage display peptide libraries) to their receptors is highly specific with high affinity, and they are generally considered less immunogenic than IgG antibodies. 26 One of the main issues investigated in this study was whether A666-NP can penetrate the RWM and accumulate to OHCs.…”

Recent advances in local drug delivery to the inner ear

“…686 Safety 687 Nanoparticulate systems tested in animals following a single intratympanic administration 688 showed a good safety profile. They did not exhibit negative effects on the hearing 689 functionand did not provoke any hair cell loss or histological damages (Scheper et al, 2009, 690 Zhang et al, 2011, Kim et al, 2014or inflammation (Zou et al, 2014). 691 However, SPIONs exhibited a neurotoxic effect by disturbing the electrical activity even at 692 low particle concentrations (Gramowski et al, 2010, Pritz et al, 2013.…”

“…formed by the self-assembly of amphiphilic block copolymers such as 601 poly(ethyleneglycol)-b-poly(Ɛ-caprolactone)(PEG-b-PCL)(Roy et al, 2012)or poly(2-602 hydroxyethyl aspartamide (PHEA)(Kim et al, 2014)in an aqueous solution.They have a 603 hydrophobic membrane surrounding an aqueous core and a hydrophilic corona.Their 604 biomimetic structure enables a good tolerance regarding the immune system. Hydrophilic 605 drugs are loaded in the core and hydrophobic ones in the membrane.606 Dendrimer-based nanoparticles 607 Dendrimers are randomly branched dendritic polymers consisting in the repetition of a 608 unique molecule.…”

Developments in Bio-Inspired Nanomaterials for Therapeutic Delivery to Treat Hearing Loss

“…Dye encapsulated PHEA showed significant uptake in the organ of Corti, with dye accumulating in inner hair cells. PHEA nanoparticles may be advantageous for the delivery of therapeutics to the inner hair cells (Kim et al, 2015). While there is no known ligand on PHEA nanoparticles to target inner hair cells, preferential accumulation in inner hair cells may be attributed to their physical and chemical properties such as the surface charge and hydrophilicity of the particles and how they bind to the surface of inner hair cells before endocytosis of the nanoparticles.…”