Intracochlear drug delivery: Fluorescent tracer evaluation for quantification of distribution in the cochlear partition.

Measurement of drug distribution in the inner ear has important roles in the design of local delivery methods, such as direct, intracochlear delivery, and in assessment of emerging drug candidates in preclinical animal models. Sampling methods have been used in the past to measure drug concentrations in the cochlear fluids, but these methods provide no direct information about drug distribution in the cochlear tissues. In this work, we evaluated four fluorescent markers that simulate drug distribution in the organ of Corti after intracochlear delivery to the cochlea's scala tympani compartment.

A fluorescence-based imaging approach to pharmacokinetic analysis of intracochlear drug delivery.

Advances in microelectromechanical systems (MEMS) technologies are enhancing the development of intracochlear delivery devices for the treatment of hearing loss with emerging pharmacological therapies. Direct intracochlear delivery addresses the limitations of systemic and intratympanic delivery. However, optimization of delivery parameters for these devices requires pharmacokinetic assessment of the spatiotemporal drug distribution inside the cochlea.

Mixed Reversible Covalent Crosslink Kinetics Enable Precise, Hierarchical Mechanical Tuning of Hydrogel Networks.

Hydrogels play a central role in a number of medical applications and new research aims to engineer their mechanical properties to improve their capacity to mimic the functional dynamics of native tissues. This study shows hierarchical mechanical tuning of hydrogel networks by utilizing mixtures of kinetically distinct reversible covalent crosslinks. A methodology is described to precisely tune stress relaxation in PEG networks formed from mixtures of two different phenylboronic acid derivatives with unique diol complexation rates, 4-carboxyphenylboronic acid, and o-aminomethylphenylboronic acid.

The role of intracochlear drug delivery devices in the management of inner ear disease.

Introduction: Diseases of the inner ear include those of the auditory and vestibular systems, and frequently result in disabling hearing loss or vertigo. Despite a rapidly expanding pipeline of potential cochlear therapeutics, the inner ear remains a challenging organ for targeted drug delivery, and new technologies are required to deliver these therapies in a safe and efficacious manner. In addition to traditional approaches for direct inner ear drug delivery, novel microfluidics-based systems are under development, promising improved control over pharmacokinetics over longer periods of delivery, ultimately with application towards hair cell regeneration in humans.

Intrinsic radiation resistance in human chondrosarcoma cells.

Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death.