Small molecule delivery across a perforated artificial membrane by thermoreversible hydrogel poloxamer 407.

Microperforations in the round window membrane have been suggested for enhancing the rate and reliability of drug delivery into the cochlea. Intratympanic injection, the most common delivery method, involves injecting therapy into the middle ear to establish a reservoir from which drug diffuses across the round window membrane into the cochlea. This process is highly variable because (i) the reservoir, if liquid, can lose contact with the membrane and (ii) diffusion across the membrane is intrinsically variable even with a stable reservoir. To address these respective sources of variability, we compared the thermoreversible hydrogel poloxamer 407 (P407) to saline as a drug carrier and studied the effect of membrane microperforations on drug diffusion rate. We used Rhodamine B as a drug proxy to measure permeance across an artificial membrane in a horizontal diffusion cell. We found that permeance of Rhodamine B from a saline reservoir was an order of magnitude higher than that from a P407 reservoir across unperforated membranes. Moreover, permeance increased with total perforation cross-sectional area regardless of number of perforations (p < 0.05 for all saline-based experiments), but the same association was not found with P407. Rather, for a P407 reservoir, only a large perforation increased permeance (p < 0.001), while multiple small perforations did not (p = 0.749). These results confirm that for drug dissolved in saline, multiple small perforations can effectively enhance diffusion. However, for drug dissolved in P407, larger perforations are necessary.

[An enlarged dismantable anatomical model of the ear by Auzoux: observation and photographical tridimensional reconstruction]. / Un modèle d'oreille agrandie, démontable par Auzoux : observation et reconstruction photographique tridimensionnelle.

The aim of the study was to determine the accuracy of a 19th century anatomical model of an ear by Auzoux (a French manufacturer). It measured 63 cm in length; 43 cm in width; 37 cm in height. The disassembled parts were studied on the morphological aspect in its whole and after removing of its components: external ear (43 cm x 23 cm x 15 cm), tympanic drum and middle ear ossicles; cochleo-vestibular apparatus. The main dimensions of each part were recorded. The arterial vascularisation of the three components of the ear and its sensitive and sensorial nervous system were established on the model which represented the external carotid artery with its terminal bifurcation, several collateral branches specially the posterior auricular artery and the middle meningeal artery; the internal carotid artery at the two extremities of the carotid canal. The cochleo-vestibular and facial nerve as well as other elements of small calibre were exactly figured and labelled by a number. The middle ear components were disassembled. The ossicles of the middle ear and a dried peritoneal tympanic membrane were dismountable as a whole. Only a few minor modification from the admitted data of anatomy as well as the cutaneous muscles of the external ear were observed on this sample, the anatomical aspects of which were very precisely represented. The material was typical of the Auzoux manner: a special papier-mâché whose conception and realization remains unequalled. This kind of very rare model can be dated at the earliest 1835 (Lemire, 1990).