Dataset Information

Local Drug Delivery for the Treatment of Neurotology Disorders.

ABSTRACT: Neurotology disorders such as vertigo, tinnitus, and hearing loss affect a significant proportion of the population (estimated 39 million in the United States with moderate to severe symptoms). Yet no pharmacological treatments have been developed, in part due to limitations in effective drug delivery to the anatomically protected inner ear compartment. Intratympanic delivery, a minimally invasive injection performed in the office setting, offers a potential direct route of administration. Currently, off-label use of therapeutics approved to treat disorders via systemic administration are being injected intratympanically, mostly in the form of aqueous solutions, but provide variable levels of drug exposure for a limited time requiring repeated injections. Hence, current drug delivery approaches for neurotology disorders are sub-optimal. This review, following a description of pharmacokinetic considerations of the inner ear, explores the merits of novel delivery approaches toward the treatment of neurotology disorders. Methodologies employing local delivery to the inner ear are described, including direct intracochlear delivery as well as intratympanic methods of infusion and injection. Intratympanic injection delivery formulation strategies including hydrogels, polymers and nanoparticulate systems are explored. These approaches represent progress toward more effective delivery options for the clinical treatment of a variety of neurotology disorders.

SUBMITTER: Piu F

PROVIDER: S-EPMC6557301 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Local Drug Delivery for the Treatment of Neurotology Disorders.

Piu Fabrice F Bishop Kathie M KM

Frontiers in cellular neuroscience 20190603

Neurotology disorders such as vertigo, tinnitus, and hearing loss affect a significant proportion of the population (estimated 39 million in the United States with moderate to severe symptoms). Yet no pharmacological treatments have been developed, in part due to limitations in effective drug delivery to the anatomically protected inner ear compartment. Intratympanic delivery, a minimally invasive injection performed in the office setting, offers a potential direct route of administration. Curre ...[more]

PMID: 31213983

Similar Datasets

Project description:Musculoskeletal disorders are a significant burden on the global economy and public health. Advanced drug delivery plays a key role in the musculoskeletal field and holds the promise of enhancing the repair of degenerated and injured musculoskeletal tissues. Ideally, drug delivery should have the ability to directly deliver therapeutic agents to the diseased/injured sites with a desirable drug level over a period of time. Here, we present a mini-review of the current state-of-the-art research associated with local drug delivery and its use for the treatment of musculoskeletal disorders. First, an overview of drug delivery strategies, with a focus on issues related to musculoskeletal pathology, potential therapeutic strategies, conventional and non-conventional drugs, and various delivery systems, is introduced. Then, we highlight recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering techniques), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications. STATEMENT OF SIGNIFICANCE: Three important aspects are highlighted in this manuscript: 1) The advanced musculoskeletal drug delivery is introduced from the aspects ranging from musculoskeletal disorders, potential therapeutic solutions, and various drug delivery systems. 2) The recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering technique), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery), are highlighted. 3) The challenges and perspectives of future research directions in the development of musculoskeletal local drug delivery are presented.

Project description:BackgroundBecause orthodontic tooth movement is dependent upon osteoclast-mediated resorption of alveolar bone adjacent to the pressure side of tooth roots, biologic mediators that regulate osteoclasts can be utilized to control tooth movement.ObjectivesTo develop a novel method to locally enhance orthodontic anchorage.MethodsWe encapsulated osteoprotegerin (OPG) in polymer microspheres and tested the effectiveness of microsphere encapsulated versus non-encapsulated OPG for enhancing orthodontic anchorage in a rodent model of tooth movement. A single injection of 1 mg/kg non-encapsulated or microsphere encapsulated OPG was delivered into the palatal mucosa mesial to the first maxillary molar 1 day prior to tooth movement. A positive control group received injections of 5 mg/kg non-encapsulated OPG every 3 days during tooth movement. After 28 days of tooth movement, hemi-maxillae and femurs were dissected. Molar mesial and incisor distal tooth movement was measured using stone casts that were scanned and magnified. Local alveolar, distant femur bone, and tooth root volumes were analyzed by micro computed tomography. Serum OPG levels were measured by ELISA. Osteoclast numbers were quantified by histomorphometry.ResultsThe single injection of microsphere encapsulated OPG significantly enhanced orthodontic anchorage, while the single injection of non-encapsulated OPG did not. Injection of encapsulated OPG inhibited molar mesial movement but did not inhibit incisor tooth movement, and did not alter alveolar or femur bone volume fraction, density, or mineral content. Multiple injections of 5 mg/kg non-encapsulated OPG enhanced orthodontic anchorage, but also inhibited incisor retraction and altered alveolar and femur bone quality parameters. Increased OPG levels were found only in animals receiving multiple injections of non-encapsulated 5 mg/kg OPG. Osteoclast numbers were higher upon tooth movement in animals that did not receive OPG. Osteoclast numbers in OPG injected animals were variable within groups.ConclusionsMicrosphere encapsulation of OPG allows for controlled drug release, and enhances site-specific orthodontic anchorage without systemic side effects. With additional refinements, this drug delivery system could be applicable to a broad array of potential biologic orthodontic therapeutics.

Dataset Information

Local Drug Delivery for the Treatment of Neurotology Disorders.

Publications

Local Drug Delivery for the Treatment of Neurotology Disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets