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In vivo biodistribution and ototoxicity assessment of cationic liposomal-ceftriaxone via noninvasive trans-tympanic delivery in chinchilla models: Implications for otitis media therapy. Int J Pediatr Otorhinolaryngol 2024 Mar;178:111894

Date

02/14/2024

Pubmed ID

38350381

Pubmed Central ID

PMC10939715

DOI

10.1016/j.ijporl.2024.111894

Scopus ID

2-s2.0-85185718661 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

OBJECTIVES: We report the in vivo biodistribution and ototoxicity of cationic liposomal-ceftriaxone (CFX) delivered via ear drop formulation in adult chinchilla.

METHODS: CFX was encapsulated in liposomes with size of ∼100 nm and surface charge of +20 mV. 100 μl liposomes or free drug was applied twice daily in both external ear canals of adult chinchillas for either 3 or 10 days. Study groups included free ceftriaxone (CFX, Day 3: n = 4, Day 10: n = 8), liposomal ceftriaxone (CFX-Lipo, Day 3: n = 4, Day 10: n = 8), and a systemic control group (Day 3: n = 4, Day 10: n = 4). Ceftriaxone delivery to the middle ear and systemic circulation was quantified by HPLC assays. Liposome transport was visualized via confocal microscopy. Auditory brainstem response (ABR) tests and cochlear histology were used to assess ototoxicity.

RESULTS: Liposomal ceftriaxone (CFX-Lipo) displayed a ∼658-fold increase in drug delivery efficiency in the middle ear relative to the free CFX (8.548 ± 0.4638% vs. 0.013 ± 0.0009%, %Injected dose, Mean ± SEM). CFX measured in blood serum (48.2 ± 7.78 ng/ml) following CFX-Lipo treatment in ear was 41-fold lower compared to systemic free-CFX treatment (1990.7 ± 617.34 ng/ml). ABR tests and histological analysis indicated no ototoxicity due to the treatment.

CONCLUSION: Cationic liposomal encapsulation results in potent drug delivery across the tympanic membrane to the middle ear with minimal systemic exposure and no ototoxicity.

Author List

Shafiee S, Hong W, Lucas J, Khampang P, Runge CL, Wells C, Yan K, Kerschner JE, Joshi A

Authors

Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Shayan Shafiee Postdoctoral Researcher in the Biomedical Engineering department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Ceftriaxone
Chinchilla
Ear, Middle
Humans
Liposomes
Otitis Media
Tissue Distribution
Tympanic Membrane