Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

Abstract

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss

“…Several drug delivery vehicles have been explored to extend the middle ear residence time and enhance the delivery concentration to the inner ear. Notable examples include gelatin, poloxamer, chitosan, collagen, and click-cross-linked HA, all of which offer certain advantages ( Gausterer et al, 2020 ; Li et al, 2020 ; Park et al, 2020 ; Cho et al, 2021 ; Le et al, 2023 ; Lei et al, 2023 ). However, most of these agents had residence times ranging of a mere 1–21 days.…”

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss

“…The downside of IT drug delivery is middle ear infection. Various biocompatible materials and drugs that are safe in other organs can cause inflammation and/or infection in the structurally vulnerable TM [ 47 , 48 ]. Therefore, we evaluated the macroscopic and microscopic changes induced by IT delivery of dieckol.…”

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

“…HA is characterized by a strong water binding ability and is found in the extracellular matrix [ 90 ]. HA has been used to deliver anti-bacterial drugs [ 99 ], immunosuppressants [ 100 ], anabolic and anti-inflammatory compounds [ 70 , 101 , 102 , 103 , 104 ]. The delivery of chemotherapeutics using hyaluronic acid have been well-studied [ 105 , 106 , 107 , 108 ].…”

“…Additionally, anti-oxidants [ 115 ], flavonols [ 116 ], anti-photoaging agents [ 117 ], and peptides [ 118 ] have been delivered using HA. Furthermore, HA has been used to deliver cells (including cell secretome) [ 119 , 120 ], genetic material [ 112 ], growth factors [ 102 , 121 ], and hormones [ 122 ].…”