The inner ear is a relatively isolated organ, protected by the blood-labyrinth barrier (BLB). This barrier creates a unique lymphatic fluid environment within the inner ear, maintaining a stable physiological state essential for the mechano-electrical transduction process in the inner ear hair cells while simultaneously restricting most drugs from entering the lymphatic fluid. Under pathological conditions, dysfunction of the stria vascularis and disruption in barrier structure can lead to temporary or permanent hearing impairment. This review describes the structure and function of the BLB, along with recent advancements in modeling and protective studies related to the BLB. The review emphasizes some newly developed non-invasive inner ear drug delivery strategies, including ultrasound therapy assisted by microbubbles, inner ear-targeting peptides, sound therapy, and the route of administration of the cerebrospinal fluid conduit. We argue that some intrinsic properties of the BLB can be strategically utilized for effective inner ear drug delivery.

The calcium- and integrin-binding protein (CIB) family, comprising four evolutionarily conserved members (CIB1, CIB2, CIB3, and CIB4), is characterized by canonical EF-hand motifs. The functions of CIBs in the inner ear have been investigated, although further research is still necessary to gain a comprehensive understanding of them. Among the CIB family members, CIB2 is essential for auditory function. CIB3 and CIB2 jointly participate in the regulation of balance. Beyond their sensory roles, CIBs exhibit multifunctionality through calcium-dependent interactions with diverse molecular partners, contributing to the pathogenesis of various conditions, including neurological disorders, cardiovascular diseases, cancer, and male infertility. In this review, we discuss the conserved structure of the CIB family, highlighting its contributions to various biological functions. We also summarize the distribution and function of the CIB family, emphasizing the pivotal roles of CIB2 and CIB3 in hearing and balance.

The inner ear is a relatively isolated organ, protected by the blood-labyrinth barrier (BLB). This barrier creates a unique lymphatic fluid environment within the inner ear, maintaining a stable physiological state essential for the mechano-electrical transduction process in the inner ear hair cells while simultaneously restricting most drugs from entering the lymphatic fluid. Under pathological conditions, dysfunction of the stria vascularis and disruption in barrier structure can lead to temporary or permanent hearing impairment. This review describes the structure and function of the BLB, along with recent advancements in modeling and protective studies related to the BLB. The review emphasizes some newly developed non-invasive inner ear drug delivery strategies, including sound therapy, ultrasound therapy assisted by microbubbles, inner ear-targeting peptides and route of administration cerebrospinal fluid conduit. We argue that some intrinsic properties of the BLB can be strategically utilized for effective inner ear drug delivery.