Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear

Kechai, Naila El; Mamelle, Elisabeth; Nguyen, Yann; Huang, Nicolas; Nicolas, Valérie; Chaminade, Pierre; Yen-Nicolaÿ, Stéphanie; Gueutin, Claire; Granger, Benjamin; Ferrary, Évelyne; Agnely, Florence; Bochot, Amélie

doi:10.1016/j.jconrel.2016.02.013

Cited by 76 publications

(57 citation statements)

References 42 publications

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“…El Kechai et al 19 employed this method to evaluate the permeability of hyaluronic acid liposomal gel, but a small number of RWM samples was obtained due to immature sampling technology, despite having many involved animals. Actually, the integrity of RWM would not collapse during the extraction of the surrounding bone, which increases the success Figure 6 TeM images of rWM in the control group and intratympanic injection of Plga NPs group.…”

Section: Discussionmentioning

confidence: 99%

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Zhang¹,

Xu²,

Cao³

et al. 2018

IJN

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Background The round window membrane (RWM) functions as the primary biological barrier for therapeutic agents in the inner ear via local application. Previous studies on inner ear nano-drug delivery systems mostly focused on their pharmacokinetics and distribution in the inner ear, but seldom on the interaction with the RWM. Clarifying the transport mechanism of nanoparticulate carriers across RWM will shed more light on the optimum design of nano-drug delivery systems intended for meeting demands for their clinical application. Methods The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) encapsulating coumarin-6 were prepared by emulsifying solvent evaporation method. We utilized confocal laser scanning microscope (CLSM) in combination with transmission electron microscope to investigate the transport pathway of PLGA NPs in the RWM. Simultaneously, the concentration and time dependence of NPs across the RWM were also determined. The endocytic mechanism of NPs through this membrane interface was classically analyzed by means of various endocytic inhibitors. The intracellular location of NPs into lysosomes was evaluated using CLSM scanning microscope colocalization analysis. The Golgi-related inhibitors were employed to probe into the function of Golgi and endoplasmic reticulum (ER) in the discharge of NPs out of cells. Results PLGA NPs were herein transported through the RWM of a sandwich-like structure into the perilymph via the transcellular pathway. NPs were internalized predominantly via macropinocytosis and caveolin-mediated endocytic pathways. After being internalized, the endocytosed cargos were entrapped within the lysosomal compartments and/or the endoplasmic reticulum/Golgi apparatus which mediated the exocytotic release of NPs. Conclusion For the first time, we showed the translocation itinerary of NPs in RWM, providing a guideline for the rational fabrication of inner ear nanoparticulate carriers with better therapeutic effects.

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Section: Discussionmentioning

confidence: 99%

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Zhang¹,

Xu²,

Cao³

et al. 2018

IJN

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“…The IT approach involves injection of a drug into the middle ear through the tympanic membrane and is less invasive than the intracochlear approach. The delivery efficiency or sustained delivery via the round window membrane (RWM) can be improved using materials and devices such as hydrogels, nanoparticles, MicroWick, microcatheters, and hyaluronic acid liposomal gels …”

Section: Introductionmentioning

confidence: 99%

“…The delivery efficiency or sustained delivery via the round window membrane (RWM) can be improved using materials and devices such as hydrogels, nanoparticles, MicroWick, microcatheters, and hyaluronic acid liposomal gels. [10][11][12][13] We previously demonstrated an enhancement of trans-RWM drug delivery by sonophoresis with ultrasound (US)-aided microbubbles (MBs). 14 Therapeutic agents or medications for the cochlea often have limited access to the inner ear via the systemic blood supply because of the blood-cochlea barrier, but this technique increases the RWM permeability and facilitates drug delivery directly into the inner ear.…”

Section: Introductionmentioning

confidence: 99%

Middle‐ear dexamethasone delivery via ultrasound microbubbles attenuates noise‐induced hearing loss

et al. 2018

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Objectives/Hypothesis In this study, we expanded our previous investigation by testing the efficiency of trans–round window membrane dexamethasone (DEX) delivery mediated by ultrasound (US)‐aided microbubbles (MBs) and its preventive effects regarding noise exposure in animal models. Study Design Live animal model. Methods Forty‐two pigmented male guinea pigs were divided into the following three groups: an US‐MBs (USM) group, in which the tympanic bulla was filled with DEX and MBs and exposed to US; a round window soaking (RWS) group, without the US irradiation; and a control group. The above‐mentioned manipulations were performed 2 hours prior to white noise exposure. The cochlear damage, including auditory threshold shifts, hair cell loss, and expression of cochlear HMGB1, was evaluated. Results The enhanced DEX delivery efficiency of the USM group was approximately 2.4× to 11.2× greater than that of the RWS group. After the noise exposure, the RWS group showed significant cochlear protection compared with the control group, and more significant and dominant protective effects were demonstrated in the USM group. Conclusions The application of US‐MBs provides a safe and more effective approach than spontaneous diffusion, which is commonly used in clinical practice; thus, this technique holds potential for future inner‐ear drug delivery. Level of Evidence NALaryngoscope, 129:1907–1914, 2019

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“…Surface modification of PLGA nanoparticles with hydrophilic molecules such as poloxamer can further improve cellular uptake . Liposomes loaded with the prodrug dexamethasone phosphate and deposited into hyaluronic acid gel also demonstrated sustained delivery of dexamethasone with reduced eustachian tube clearance . These liposomes remain in hyaluronic acid adjacent to the RWM, creating a local reservoir that allowed sustained release of dexamethasone into the perilymph over 30 days, with increased conversion of dexamethasone phosphate to active dexamethasone.…”

Section: Optimal Inner Ear Delivery Methodsmentioning

confidence: 99%

“…However, further development was suspended after OTO‐104 failed to demonstrate benefit over placebo. A variety of other hydrogels, including chitosan glycerophosphate and hyaluronic acid, has been studied extensively with similar safety and efficacy …”

Section: Recent Advances In Inner Ear Deliverymentioning

confidence: 99%

Inner ear delivery: Challenges and opportunities

Szeto

Chiang

Valentini

et al. 2019

Laryngoscope Investig Oto

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Objectives The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies for overcoming these barriers and to discuss promising future avenues for investigation. Data Sources The databases used were PubMed, EMBASE, and Web of Science. Results Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants. Conclusions In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation. Level of Evidence NA

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Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear

Cited by 76 publications

References 42 publications

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Middle‐ear dexamethasone delivery via ultrasound microbubbles attenuates noise‐induced hearing loss

Inner ear delivery: Challenges and opportunities

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