Novel Nanoencapsulation Technology and its Potential Role in Bile Acid‐Based Targeted Gene Delivery to the Inner Ear

Foster, Thomas S.; Lewkowicz, Michael; Quintas, Christina; Ionescu, Corina Mihaela; Jones, Melissa; Wagle, Susbin Raj; Kovačević, Božica; Wong, Elaine YM; Mooranian, Armin; Al‐Salami, Hani

doi:10.1002/smll.202204986

Cited by 7 publications

(1 citation statement)

References 142 publications

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“…Despite significant achievements in pharmacological therapies, gene therapies, and regenerative approaches, there is no FDA‐approved medication available for alleviating noise‐induced hearing loss (NIHL). [ 1 ] The cochlea's isolated anatomical position contributes to inefficient drug concentration in the inner ear. [ 2 ] While the intratympanic route can bypass the blood‐labyrinth barrier, and nanotechnologies can facilitate drug penetration through the round window membrane (RWM), the limited uptake by target cells, and the degradation or clearance of nanocarriers in the perilymph, are currently recognized as critical issues.…”

Section: Introductionmentioning

confidence: 99%

Gelatin‐Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise‐Induced Hearing Loss

Xu,

Du,

et al. 2024

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Nanoparticle‐based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug‐delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise‐induced hearing loss via loading epigallocatechin gallate (EGCG) with anti‐lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell‐particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG‐loaded nanosystem (TDN‐EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN‐EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.

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Section: Introductionmentioning

confidence: 99%

Gelatin‐Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise‐Induced Hearing Loss

Xu,

Du,

et al. 2024

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Polymer‐Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy

Foster,

Lim,

Jones

et al. 2024

ChemMedChem

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Hearing loss is a significant disability that often goes under recognised, largely due to poor identification, prevention, and treatment. Steps are being made to amend these pitfalls in the investigation of hearing loss, however, the development of a cure to reverse advanced forms remains distant. This review details some current advances in the treatment of hearing loss, with a particular focus on genetic‐based nanotechnology and how it may provide a useful avenue for further research. This review presents a broad background on the pathophysiology of hearing loss and some current interventions. We also highlight some potential genes that may be useful in the amelioration of hearing loss. Pathways of cellular differentiation from stem or supporting cell to functional hair cell are covered in detail, as this mechanism represents a key means of regenerating these cell types. Overall, we believe that polymer‐based nanotechnology coupled with novel excipients represents a useful area of further research in the treatment of hearing loss, although further studies in this area are required.

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Effect of ursodiol on alginate/PLL nanoparticles with non-ionic surfactant for gene delivery

Foster,

Lim,

Kovacevic

et al. 2024

J Nanopart Res

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Hearing loss is a widespread condition, affecting people from a range of demographics. Gene therapy is an emerging method for the amelioration of this condition. Challenges associated with the delivery of genes to various sites within the ear remain a significant challenge. In the present work, a novel polymer nanoparticle delivery system was developed, incorporating a bile acid excipient. Bile acids have previously been shown to improve drug delivery through their permeation enhancing properties; however, few studies report their use in gene delivery systems. Nanoparticles were developed with sodium alginate and poly-L-lysine through an ionotropic gelation method. Various surfactants including Tween-80 and poly-ethylene glycol 6000 were incorporated to both improve the solubility of the bile acid, ursodiol, and to modify nanoparticle properties. The evaluation of the nanoparticle’s safety profiles was the primary outcome of this study. The secondary aims were to perform genetic studies, such as transfection efficiency. The nanoparticles generated in this study demonstrated formulation-dependent variability in particle size ranging from 30 to 300 nm. Several of the developed formulations demonstrated suitable safety profiles; further, the introduction of bile acid helped to reduce toxicity. Transfection efficiency for all formulations remained low, potentially due to poor plasmid release inside the cell. Poor transfection efficiency is one of the key pitfalls associated with polymer nanoparticles Overall the present study developed nanoparticles with suitable safety profiles but limited efficacy. The use of modified polymers, additional excipients, and cell-targeting peptides are potential methods that may be explored in future studies to help further improve gene delivery.

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Novel Nanoencapsulation Technology and its Potential Role in Bile Acid‐Based Targeted Gene Delivery to the Inner Ear

Abstract: The ear is composed of three separate regions, the outer, middle and inner ear. Each serves a specific function to aid in the conversion of air compressions into nerve impulses. The outer ear primarily serves to concentrate sound to the tympanic

Cited by 7 publications

References 142 publications

Gelatin‐Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise‐Induced Hearing Loss

Gelatin‐Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise‐Induced Hearing Loss

Polymer‐Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy

Effect of ursodiol on alginate/PLL nanoparticles with non-ionic surfactant for gene delivery

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