High variability of perilymphatic entry of neutral molecules through the round window
| Autor: | Larbi Chelikh, Christian Martin, Evelyne Ferrary, Vincent Couloigner, Marie Teixeira, Olivier Sterkers |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Administration Topical High variability Guinea Pigs Biological Availability Perilymph Sensitivity and Specificity Drug Administration Schedule Cerebrospinal fluid Osmotic minipump Medicine Animals Inner ear Mannitol Probability Radioisotopes Round window business.industry Inulin Perilymphatic space General Medicine Constant rate Disease Models Animal medicine.anatomical_structure Otorhinolaryngology Round Window Ear business Biomedical engineering |
| Zdroj: | Acta oto-laryngologica. 123(2) |
| ISSN: | 0001-6489 |
| Popis: | To improve the efficacy of intratympanic therapy using perilymphatic entry through the round window membrane.The perilymphatic entry characteristics of 2 neutral molecules, mannitol (182.2 Da) and inulin (7,000 Da), were studied. A polyethylene catheter was placed in contact with the guinea pig round window membrane and sealed with cyanoacrylate glue. This catheter was linked to an osmotic minipump that delivered 100 microl portions of 3H-mannitol or 3H-inulin solutions over a 7-day period at a constant rate (0.5 microl/h). Perilymph in the scala vestibuli and scala tympani, cerebrospinal fluid (CSF) and plasma were sampled after 4-7 days of delivery.Despite the constant rate of infusion, perilymphatic radioactivity varied widely from one animal to the other, probably as a function of the position of the microcatheter within the round window niche and/or the permeability of the round window. Even a large molecule such as inulin entered the perilymphatic space. Seven days after the beginning of 3H-mannitol administration, the radioactivity was higher in the perilymph of the scala tympani than in that of the scala vestibuli. The perilymphatic radioactivity on Day 7 was approximately 50% lower than that measured on Day 4 (p = NS). Finally, round window membrane delivery did not preclude distant spread of the molecules into the blood and CSF.Using round window membrane delivery, the perilymphatic entry of mannitol and inulin depended on their molecular weight. Intratympanic delivery induced a high inter-individual heterogeneity of the drug concentration within the inner ear, with subsequent variability of the therapeutic effects. |
| Databáze: | OpenAIRE |
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