Controlled drug release to the inner ear: Concepts, materials, mechanisms, and performance

Mäder, Karsten; Lehner, Eric; Liebau, Arne; Plontke, Stefan K.

doi:10.1016/j.heares.2018.03.006

Cited by 75 publications

(55 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of the blood-labyrinth barrier hampers systemic drug administration to the inner ear; therefore, the different methods and devices for enhancing local drug delivery have been devised for improving medical therapies for inner ear diseases (38). Most of these delivery devices and drug carriers are applied via the external auditory canal.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery

Liao¹,

Wang²,

Weng³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery

Liao¹,

Wang²,

Weng³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

“…The 5% GelMA hydrogels degraded within 3 h, while 10% and 15% GelMA followed a similar degradation rate for the first four hours and completely degraded after 6 h and 8 h, respectively. The linearity of the hydrogel degradation rate suggests a near zero-order degradation kinetic which occurs when the rate of hydrogel bond cleavage is faster than the diffusion rate of the enzyme solution through the hydrogel and is characteristic of a surface erosion [50,51,70,71]. Enzymatic release of the drug followed a similar trend; however, degradation was slower compared to GelMA alone, and the GelMA-DDS degraded within 2 h, 8 h, and 14 h for 5%, 10%, and 15% GelMA, respectively, irrespective of the Abraxane ® dose.…”

Section: Release Through Enzymatic Degradationmentioning

confidence: 99%

Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel

et al. 2020

View full text Add to dashboard Cite

Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-based drug delivery system (GelMA-DDS) for the sustained local delivery of paclitaxel-based Abraxane®, for the prevention of local breast cancer recurrence following mastectomy. GelMA-DDS readily encapsulated Abraxane® with a maximum of 96% encapsulation efficiency. The mechanical properties of the hydrogel system were not affected by drug loading. Tuning of the physical properties, by varying GelMA concentration, allowed tailoring of GelMA-DDS mesh size, where decreasing the GelMA concentration provided overall more sustained cumulative release (significant differences between 5%, 10%, and 15%) with a maximum of 75% over three months of release, identified to be released by diffusion. Additionally, enzymatic degradation, which more readily mimics the in vivo situation, followed a near zero-order rate, with a total release of the cargo at various rates (2–14 h) depending on GelMA concentration. Finally, the results demonstrated that Abraxane® delivery from the hydrogel system led to a dose-dependent reduction of viability, metabolic activity, and live-cell density of triple-negative breast cancer cells in vitro. The GelMA-DDS provides a novel and simple approach for the sustained local administration of anti-cancer drugs for breast cancer recurrence.

show abstract

“…Local administration provides the advantage of precise targeting and avoids the risk of systemic adverse events (El Kechai et al, 2015;Li et al, 2017;Hao and Li, 2019;Piu and Bishop, 2019). The methods of local drug administration to the inner ear include intratympanic and intracochlear approaches, where the latter offers a direct delivery route to achieve a greater drug bioavailability by either penetrating right through the round window membrane (RWM) or through an opening in the cochlear bony wall (El Kechai et al, 2015;Mäder et al, 2018). However, the intracochlear approach poses a high risk of inner ear damage and hearing loss and is therefore mainly employed as a combined procedure during cochlear implant surgery (Mccall et al, 2010;Chin and Diaz, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…To overcome the short residence times for contact with the RWM, several delivery devices, such as the MicroWick, microcathers, and osmotic pumps, have been developed to prolong the duration of medication contact with the RWM. Delivery materials and agents such as gelfoam, hyaluronic acid hydrogels, histamine, nanoparticles, and nanovesicles can also provide a sustained inner ear delivery via the RWM (El Kechai et al, 2015;Mäder et al, 2018;Creber et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural Changes Associated With the Enhanced Permeability of the Round Window Membrane Mediated by Ultrasound Microbubbles

Lin

Chen

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

The round window membrane (RWM) is the most common entryway for local drug and gene delivery into the inner ear, but its permeability can change the treatment outcome. We previously demonstrated a feasible and highly efficient approach using ultrasound-aided microbubble (USMB) cavitation to enhance the permeability of the RWM. Here, we investigated the safety of USMB exposure and the association between temporal changes in RWM permeability and ultrastructure. Experimental guinea pigs were divided into two treatment groups: a control group receiving round window soaking (RWS) with MBs and treatment (USM) groups undergoing 3 (USM-3) or 5 (USM-5) consecutive USMB exposures (1 min/exposure) at an acoustic intensity of 3 W/cm 2 and 1 MHz frequency. The trans-RWM delivery efficiency of biotin-fluorescein isothiocyanate conjugates, used as permeability tracers, revealed a greater than 7-fold higher delivery efficiency for the USM groups immediately after 3 or 5 exposures than for the RWS group. After 24 h, the delivery efficiency was 2.4-fold higher for the USM-3 group but was 6.6-fold higher for the USM-5 group (and 3.7-fold higher after 48 h), when compared to the RWS group. Scanning electron microscopy images of the RWM ultrastructure revealed USMB-induced sonoporation effects that could include the formation of heterogeneous pore-like openings with perforation diameters from 100 nm to several micrometers, disruption of the continuity of the outer epithelial surface layer, and loss of microvilli. These ultrastructural features were associated with differential permeability changes that depended on the USMB exposure course. Fourteen days after treatment, the pore-like openings had significantly decreased in number and the epithelial defects were healed either by cell expansion or by repair by newly migrated epithelial cells. The auditory brainstem response recordings of the animals following the 5-exposure USMB treatment indicated no deterioration in the hearing thresholds at a 2-month follow-up and no significant hair cell damage or apoptosis, based on scanning electron microscopy, surface preparations, and TUNEL assays. USMBs therefore appear to be safe and effective for inner ear drug delivery. The mechanism of enhanced permeability may involve a disruption of the continuity of the outer RWM epithelial layer, which controls transmembrane transport of various substances.

show abstract

Controlled drug release to the inner ear: Concepts, materials, mechanisms, and performance

Cited by 75 publications

References 127 publications

Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery

Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery

Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel

Ultrastructural Changes Associated With the Enhanced Permeability of the Round Window Membrane Mediated by Ultrasound Microbubbles

Contact Info

Product

Resources

About