Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Venkatesan Perumal; Arun Reddy Ravula; Ningning Shao; Namas Chandra

doi:10.1016/j.joto.2022.09.002

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

J Otol. 2023 Jan;18(1):38-48. doi: 10.1016/j.joto.2022.09.002. Epub 2022 Oct 4.

Authors

Venkatesan Perumal¹, Arun Reddy Ravula¹, Ningning Shao¹, Namas Chandra¹

Affiliation

¹ Center for Injury Biomechanics, Materials, and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.

Abstract

Blast injuries are common among the military service members and veterans. One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss. Treating hearing loss using minocycline is restricted by optimal drug concentration, route of administration, and its half-life. Therefore, therapeutic approach using novel therapeutic delivery method is in great need. Among the different delivery methods, nanotechnology-based drug delivery is desirable, which can achieve longer systemic circulation, pass through some biological barriers and specifically targets desired sites. The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system. The I.v. administered nanoparticle at reduced dose and frequency than regularly administered toxic dose. After moderate blast exposure, rats had hearing impairment as determined by ABR at 7- and 30-days post exposure. In chronic condition, free minocycline also showed the significant reduction in ABR threshold. In central auditory system, it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus; and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration. The study demonstrated that in moderate blast induced hearing loss, minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system. In conclusion, targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.

Keywords: 5-HsT, 5-hydroxytryptamine; ABR, auditory brainstem response; AC, auditory cortex; Blast injury and targeted drug delivery; CAS, central auditory system; DAI, (diffuse axonal injury); GABA, gamma-aminobutyric acid; HL, (Hearing loss); Hearing loss; Minocycline; NMDAR1, N-methyl-D-aspartate receptor 1; Nanoparticle; PAS, peripheral auditory system; bTBI, blast traumatic brain injury.