Inviting an author to review:
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Inner ear delivery: Challenges and opportunities

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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

          Related collections

          Most cited references95

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Liposomes as nanomedical devices

          Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Clinical Practice Guideline: Sudden Hearing Loss (Update)

            Sudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently but not universally accompanied by tinnitus and/or vertigo. Sudden sensorineural hearing loss affects 5 to 27 per 100,000 people annually, with about 66,000 new cases per year in the United States. This guideline update provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with sudden hearing loss. It focuses on sudden sensorineural hearing loss in adult patients aged ≥18 years and primarily on those with idiopathic sudden sensorineural hearing loss. Prompt recognition and management of sudden sensorineural hearing loss may improve hearing recovery and patient quality of life. The guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss. The purpose of this guideline update is to provide clinicians with evidence-based recommendations in evaluating patients with sudden hearing loss and sudden sensorineural hearing loss, with particular emphasis on managing idiopathic sudden sensorineural hearing loss. The guideline update group recognized that patients enter the health care system with sudden hearing loss as a nonspecific primary complaint. Therefore, the initial recommendations of this guideline update address distinguishing sensorineural hearing loss from conductive hearing loss at the time of presentation with hearing loss. They also clarify the need to identify rare, nonidiopathic sudden sensorineural hearing loss to help separate those patients from those with idiopathic sudden sensorineural hearing loss, who are the target population for the therapeutic interventions that make up the bulk of the guideline update. By focusing on opportunities for quality improvement, this guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. Consistent with the American Academy of Otolaryngology–Head and Neck Surgery Foundation’s “Clinical Practice Guideline Development Manual, Third Edition” (Rosenfeld et al. Otolaryngol Head Neck Surg. 2013;148[1]:S1-S55), the guideline update group was convened with representation from the disciplines of otolaryngology–head and neck surgery, otology, neurotology, family medicine, audiology, emergency medicine, neurology, radiology, advanced practice nursing, and consumer advocacy. A systematic review of the literature was performed, and the prior clinical practice guideline on sudden hearing loss was reviewed in detail. Key Action Statements (KASs) were updated with new literature, and evidence profiles were brought up to the current standard. Research needs identified in the original clinical practice guideline and data addressing them were reviewed. Current research needs were identified and delineated. The guideline update group made strong recommendations for the following: (KAS 1) Clinicians should distinguish sensorineural hearing loss from conductive hearing loss when a patient first presents with sudden hearing loss. (KAS 7) Clinicians should educate patients with sudden sensorineural hearing loss about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy. (KAS 13) Clinicians should counsel patients with sudden sensorineural hearing loss who have residual hearing loss and/or tinnitus about the possible benefits of audiologic rehabilitation and other supportive measures. These strong recommendations were modified from the initial clinical practice guideline for clarity and timing of intervention. The guideline update group made strong recommendations against the following: (KAS 3) Clinicians should not order routine computed tomography of the head in the initial evaluation of a patient with presumptive sudden sensorineural hearing loss. (KAS 5) Clinicians should not obtain routine laboratory tests in patients with sudden sensorineural hearing loss. (KAS 11) Clinicians should not routinely prescribe antivirals, thrombolytics, vasodilators, or vasoactive substances to patients with sudden sensorineural hearing loss. The guideline update group made recommendations for the following: (KAS 2) Clinicians should assess patients with presumptive sudden sensorineural hearing loss through history and physical examination for bilateral sudden hearing loss, recurrent episodes of sudden hearing loss, and/or focal neurologic findings. (KAS 4) In patients with sudden hearing loss, clinicians should obtain, or refer to a clinician who can obtain, audiometry as soon as possible (within 14 days of symptom onset) to confirm the diagnosis of sudden sensorineural hearing loss. (KAS 6) Clinicians should evaluate patients with sudden sensorineural hearing loss for retrocochlear pathology by obtaining magnetic resonance imaging or auditory brainstem response. (KAS 10) Clinicians should offer, or refer to a clinician who can offer, intratympanic steroid therapy when patients have incomplete recovery from sudden sensorineural hearing loss 2 to 6 weeks after onset of symptoms. (KAS 12) Clinicians should obtain follow-up audiometric evaluation for patients with sudden sensorineural hearing loss at the conclusion of treatment and within 6 months of completion of treatment. These recommendations were clarified in terms of timing of intervention and audiometry and method of retrocochlear workup. The guideline update group offered the following KASs as options: (KAS 8) Clinicians may offer corticosteroids as initial therapy to patients with sudden sensorineural hearing loss within 2 weeks of symptom onset. (KAS 9a) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy within 2 weeks of onset of sudden sensorineural hearing loss. (KAS 9b) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy as salvage therapy within 1 month of onset of sudden sensorineural hearing loss. Incorporation of new evidence profiles to include quality improvement opportunities, confidence in the evidence, and differences of opinion Included 10 clinical practice guidelines, 29 new systematic reviews, and 36 new randomized controlled trials Highlights the urgency of evaluation and initiation of treatment, if treatment is offered, by emphasizing the time from symptom occurrence Clarification of terminology by changing potentially unclear statements; use of the term sudden sensorineural hearing loss to mean idiopathic sudden sensorineural hearing loss to emphasize that >90% of sudden sensorineural hearing loss is idiopathic sudden sensorineural hearing loss and to avoid confusion in nomenclature for the reader Changes to the KASs from the original guideline: KAS 1—When a patient first presents with sudden hearing loss, conductive hearing loss should be distinguished from sensorineural. KAS 2—The utility of history and physical examination when assessing for modifying factors is emphasized. KAS 3—The word “routine” is added to clarify that this statement addresses nontargeted head computerized tomography scan that is often ordered in the emergency room setting for patients presenting with sudden hearing loss. It does not refer to targeted scans, such as temporal bone computerized tomography scan, to assess for temporal bone pathology. KAS 4—The importance of audiometric confirmation of hearing status as soon as possible and within 14 days of symptom onset is emphasized. KAS 5—New studies were added to confirm the lack of benefit of nontargeted laboratory testing in sudden sensorineural hearing loss. KAS 6—Audiometric follow-up is excluded as a reasonable workup for retrocochlear pathology. Magnetic resonance imaging, computerized tomography scan if magnetic resonance imaging cannot be done, and, secondarily, auditory brainstem response evaluation are the modalities recommended. A time frame for such testing is not specified, nor is it specified which clinician should be ordering this workup; however, it is implied that it would be the general or subspecialty otolaryngologist. KAS 7—The importance of shared decision making is highlighted, and salient points are emphasized. KAS 8—The option for corticosteroid intervention within 2 weeks of symptom onset is emphasized. KAS 9—Changed to KAS 9A and 9B. Hyperbaric oxygen therapy remains an option but only when combined with steroid therapy for either initial treatment (9A) or salvage therapy (9B). The timing of initial therapy is within 2 weeks of onset, and that of salvage therapy is within 1 month of onset of sudden sensorineural hearing loss. KAS 10—Intratympanic steroid therapy for salvage is recommended within 2 to 6 weeks following onset of sudden sensorineural hearing loss. The time to treatment is defined and emphasized. KAS 11—Antioxidants were removed from the list of interventions that the clinical practice guideline recommends against using. KAS 12—Follow-up audiometry at conclusion of treatment and also within 6 months posttreatment is added. KAS 13—This statement on audiologic rehabilitation includes patients who have residual hearing loss and/or tinnitus who may benefit from treatment. Addition of an algorithm outlining KASs Enhanced emphasis on patient education and shared decision making with tools provided to assist in same
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Pathophysiology of the cochlear intrastrial fluid-blood barrier (review).

              The blood-labyrinth barrier (BLB) in the stria vascularis is a highly specialized capillary network that controls exchanges between blood and the intrastitial space in the cochlea. The barrier shields the inner ear from blood-born toxic substances and selectively passes ions, fluids, and nutrients to the cochlea, playing an essential role in the maintenance of cochlear homeostasis. Anatomically, the BLB is comprised of endothelial cells (ECs) in the strial microvasculature, elaborated tight and adherens junctions, pericytes (PCs), basement membrane (BM), and perivascular resident macrophage-like melanocytes (PVM/Ms), which together form a complex "cochlear-vascular unit" in the stria vascularis. Physical interactions between the ECs, PCs, and PVM/Ms, as well as signaling between the cells, is critical for controlling vascular permeability and providing a proper environment for hearing function. Breakdown of normal interactions between components of the BLB is seen in a wide range of pathological conditions, including genetic defects and conditions engendered by inflammation, loud sound trauma, and ageing. In this review, we will discuss prevailing views of the structure and function of the strial cochlear-vascular unit (also referred to as the "intrastrial fluid-blood barrier"). We will also discuss the disrupted homeostasis seen in a variety of hearing disorders. Therapeutic targeting of the strial barrier may offer opportunities for improvement of hearing health and amelioration of auditory disorders. This article is part of a Special Issue entitled .
                Bookmark

                Author and article information

                Contributors
                anil.lalwani@columbia.edu
                Journal
                Laryngoscope Investig Otolaryngol
                Laryngoscope Investig Otolaryngol
                10.1002/(ISSN)2378-8038
                LIO2
                Laryngoscope Investigative Otolaryngology
                John Wiley & Sons, Inc. (Hoboken, USA )
                2378-8038
                11 December 2019
                February 2020
                : 5
                : 1 ( doiID: 10.1002/lio2.v5.1 )
                : 122-131
                Affiliations
                [ 1 ] Department of Otolaryngology–Head and Neck Surgery Columbia University Vagelos College of Physicians and Surgeons New York New York
                [ 2 ] Department of Mechanical Engineering, School of Engineering Columbia University New York New York
                Author notes
                [*] [* ] Correspondence

                Anil K. Lalwani, Division of Otology, Neurotology, and Skull Base Surgery, Department of Otolaryngology–Head and Neck Surgery, Columbia University Vagelos College of Physicians and Surgeons, 180 Fort Washington Avenue, Harkness Pavilion, 8th Floor, New York, NY 10032.

                Email: anil.lalwani@ 123456columbia.edu

                Author information
                https://orcid.org/0000-0001-7691-312X
                Article
                LIO2336
                10.1002/lio2.336
                7042639
                21f5a7aa-5223-4e5b-8908-39db507b717b
                © 2019 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 12 September 2019
                : 21 October 2019
                : 21 November 2019
                Page count
                Figures: 5, Tables: 0, Pages: 10, Words: 8652
                Funding
                Funded by: National Institute on Deafness and Other Communication Disorders , open-funder-registry 10.13039/100000055;
                Award ID: R01DC014547
                Categories
                Otology, Neurotology, and Neuroscience
                Otology, Neurotology, and Neuroscience
                Review
                Custom metadata
                2.0
                February 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.6.1 mode:remove_FC converted:26.02.2020

                inner ear disorders,intracochlear delivery,microneedles,nanoparticles

                Comments

                Comment on this article