Veronesi Michael C, Kubek Daniel J, Kubek Michael J
Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN, USA.
Methods Mol Biol. 2011;789:303-12. doi: 10.1007/978-1-61779-310-3_20.
A major barrier to entry of neuropeptides into the brain is low bioavailability and presence of the blood-brain barrier. Intranasal delivery of neuropeptides provides a potentially promising alternative to other routes of administration, since a direct pathway exists between the olfactory neuroepithelium and the brain. Use of the rat as an animal model in nose to brain delivery of neuropeptides allows for several advantages, including a large surface area within the nasal cavity dedicated to olfactory epithelium and robust neuronal pathways extending to and from most areas of the brain from the nose via the olfactory cortex. A major disadvantage to using rats for nose to brain delivery is the difficulty in selectively targeting the posterior olfactory epithelium (which facilitates delivery to the brain) over the more anterior respiratory epithelium (which facilitates delivery to the lungs and secondarily to the peripheral blood) in the nasal cavity. We have developed a novel delivery system that consists of surgically implanting stainless-steel cannulas in the dorsal aspect of the nasal cavity overlying the olfactory neuroepithelium, thereby allowing neuropeptide compounds to bypass the respiratory epithelium.
神经肽进入大脑的一个主要障碍是生物利用度低以及血脑屏障的存在。神经肽的鼻内给药为其他给药途径提供了一种潜在的有前景的替代方法，因为嗅觉神经上皮与大脑之间存在直接通路。在神经肽的鼻至脑递送中使用大鼠作为动物模型有几个优点，包括鼻腔内有大面积专门用于嗅觉上皮，以及强大的神经元通路从鼻子通过嗅觉皮层延伸至大脑的大部分区域并从这些区域延伸回鼻子。在鼻至脑递送中使用大鼠的一个主要缺点是，在鼻腔中难以选择性地靶向位于更靠前的呼吸上皮（有利于递送至肺部并继而递送至外周血）上方的后嗅觉上皮（有利于递送至大脑）。我们开发了一种新型递送系统，该系统包括通过手术在覆盖嗅觉神经上皮的鼻腔背侧植入不锈钢套管，从而使神经肽化合物绕过呼吸上皮。
