In vivo biodistribution and ototoxicity assessment of cationic liposomal-ceftriaxone via noninvasive trans-tympanic delivery in chinchilla models: Implications for otitis media therapy.

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.

Recurrent Acute Otitis Media: What Are the Options for Treatment and Prevention?

PURPOSE OF REVIEW: To survey current strategies for treatment and prevention of recurrent acute otitis media (rAOM). RECENT FINDINGS: Treatment with systemic antibiotics is required in recurrent episodes of acute otitis media. A cautious attitude is recommended due to antibiotic resistance. Antibiotics also provide effective prophylaxis for rAOM. Topical treatment with ear drops is recommended in rAOM with otorrhea from tympanostomy tubes. Pneumococcal conjugated vaccines seem to have a moderate reductive effect on overall otitis media. The effect on rAOM is still unclear. Different administrations of immunoglobulins have not been effective against rAOM. Breastfeeding had a protective effect against rAOM. A recommendation against cigarette smoke exposure as a measure to prevent otitis seems warranted. An effect for adenoidectomy in children <2 years old with rAOM has been suggested. There is a strong genetic connection with rAOM. Probiotics and nasal spray with Streptococci might offer future opportunities as prophylaxis. Too little is known about complimentary treatments to give any recommendations. SUMMARY: Systemic antibiotics are still needed as treatment against episodes of AOM in rAOM children. There are several preventive measures that can be taken to reduce the burden of AOM but they all have a small-moderate effect. Systemic antibiotics provide effective prophylaxis in rAOM, but must be used with extreme caution due to the emerging antibiotic resistance.