In Vivo Imaging of Click-Crosslinked Hydrogel Depots Following Intratympanic Injection

Ju, Hyeon Jin; Park, Mina; Park, Ji Hoon; Shin, Gi Ru; Choi, Hak; Suh, Myung‐Whan; Kim, Moon Suk

doi:10.3390/ma13143070

Cited by 8 publications

(8 citation statements)

References 30 publications

(30 reference statements)

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“…This approach to monitor release provides a facile means to track drug release out of the depot in vivo. This is similar to other imaging methods, such as fluorescence imaging to track fluorophores mixed in hydrogel formulations [ 25 ] or magnetic resonance imaging [ 26 ] described to track T2 relaxation times of drug depots in vivo, but does not rely on fluorescently labeled drug and is much easier to use. However, tissue penetration of the drug cannot be measured with HFUS imaging.…”

Section: Discussionmentioning

confidence: 70%

Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives

Koh

Ramazani

Größ

et al. 2022

Adv Healthcare Materials

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Hydrogel‐based drug delivery systems typically aim to release drugs locally to tissue in an extended manner. Tissue adhesive alginate‐polyacrylamide tough hydrogels are recently demonstrated to serve as an extended‐release system for the corticosteroid triamcinolone acetonide. Here, the stimuli‐responsive controlled release of triamcinolone acetonide from the alginate‐polyacrylamide tough hydrogel drug delivery systems (TADDS) and evolving new approaches to combine alginate‐polyacrylamide tough hydrogel with drug‐loaded nano and microparticles, generating composite TADDS is described. Stimulation with ultrasound pulses or temperature changes is demonstrated to control the release of triamcinolone acetonide from the TADDS. The incorporation of laponite nanoparticles or PLGA microparticles into the tough hydrogel is shown to further enhance the versatility to control and modulate the release of triamcinolone acetonide. A first technical exploration of a TADDS shelf‐life concept is performed using lyophilization, where lyophilized TADDS are physically stable and the bioactive integrity of released triamcinolone acetonide is demonstrated. Given the tunability of properties, the TADDS are a suggested technology platform for controlled drug delivery.

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Section: Discussionmentioning

confidence: 70%

Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives

Koh

Ramazani

Größ

et al. 2022

Adv Healthcare Materials

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“…Various drug delivery vehicles have been used to prolong the middle ear residence time and deliver a higher concentration of drugs into the inner ear. For example, gelatin ( 34 ), poloxamer 407 ( 31 ), collagen ( 35 ), methoxy polyethylene glycol- b -polycaprolactone block copolymer ( 11 ), and click-cross-linked HA ( 36 ) have been reported to have some positive effects. However, the clinical benefits in terms of hearing gain were not sufficient in most cases, reaching 10–25 dB at best ( 11 , 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

High-Molecular-Weight Hyaluronic Acid Vehicle Can Deliver Gadolinium Into the Cochlea at a Higher Concentration for a Longer Duration: A 9.4-T Magnetic Resonance Imaging Study

Hwang

Park

et al. 2021

Front. Neurol.

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Intratympanic (IT) gadolinium (Gd) injection is one method of delivering Gd into the inner ear to evaluate the amount of endolymphatic hydrops (EH) using magnetic resonance imaging (MRI). As Gd is usually prepared in a fluid form mixed with saline, Gd injected into the middle ear drains easily through the Eustachian tube within several hours. High-molecular-weight (hMW) hyaluronic acid (HA) is an ideal vehicle for IT Gd due to its viscous and adhesive properties. The present study was performed to elucidate whether novel hMW HA is superior to conventional HA in delivering Gd into the inner ear in the short term. The second aim was to verify the long-term Gd delivery efficiency of hMW HA compared to the standard-of-care vehicle (saline). IT Gd injection and 3D T1-weighted MRI were performed in 13 rats. For the short-term study (imaging after 1, 2, and 3 h), the left ear was treated with hMW HA+Gd and the right ear with conventional HA+Gd. For the long-term study (imaging after 1, 2, 3, and 4 h, 1 – 3 days, and 7 – 10 days), the left ear was treated with hMW HA+Gd and the right ear with saline+Gd. Signal intensities (SIs) in the scala tympani (ST) and scala vestibuli (SV) were quantified. Compared to conventional HA, signal enhancement was 2.3 – 2.4 times greater in the apical and middle turns after hMW HA+Gd injection (SV at 1 h). In comparison to the standard-of-care procedure, the SI was not only greater in the short term but the higher SI also lasted for a longer duration. On days 7 – 10 after IT Gd delivery, the SI in the basal turn was 1.9 – 2.1 times greater in hMW HA+Gd-treated ears than in saline IT Gd-treated ears. Overall, hMW HA may be a useful vehicle for more efficient IT Gd delivery. Gd enhancement in the cochlea improved approximately two-fold when hMW HA was used. In addition, this greater enhancement lasted for up to 7 – 10 days. Repeated MRI of EH may be possible for several days with a single IT hMW HA+Gd delivery.

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“…For example, hydrogels could encapsulate drugs and nanoparticles and released drugs in a sustained manner in the middle ear. In previous studies, various hydrogels, such as thermoreversible poloxamer hydrogel, 12 hyaluronic acid click-cross-linked hydrogel, 13 and photosensitive GelMA hydrogel, 14 have been applied in acquired deafness, as these hydrogels can effectively increase the concentration of drugs in perilymph and improve the therapeutic effect. However, current drug delivery vehicles typically consist of bulk materials, which by itself might lead to aural fullness and long-term conductive hearing loss through intratympanic administration.…”

Section: ■ Introductionmentioning

confidence: 99%

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Wang

et al. 2022

ACS Appl. Mater. Interfaces

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Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs.

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In Vivo Imaging of Click-Crosslinked Hydrogel Depots Following Intratympanic Injection

Cited by 8 publications

References 30 publications

Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives

Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives

High-Molecular-Weight Hyaluronic Acid Vehicle Can Deliver Gadolinium Into the Cochlea at a Higher Concentration for a Longer Duration: A 9.4-T Magnetic Resonance Imaging Study

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

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