Nose-to-Brain Delivery

TABLE 4 Nose-to-Brain Delivery of Agents in Different Species... 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

Peptide YY (PYY) is a peptide hormone produced by L-cells in the intestinal tract after eating. It appears to act centrally to diminish appetite. It may serve normally to produce a sense of satiety. Diminished PYY production would be expected to cause increase in appetite and increased food intake. Hence, a biologically active PYY derivative, PYY 3-36, is under investigation as a potential agent to treat obesity and type 2 diabetes. A nasal PYY 3-36 product, if developed, would be an attractive alternative to injected PYY 3-36 because of the rapid and direct nose-to-brain drug transport that occurs following nasal drug delivery. 

Shah BM, Misra M, Shishoo CJ, Padh H. Nose to brain microemulsion-based drug deUvery system of rivastigmine Formulation and ex-vivo characterization. Drug Delivery. 2014 1-13. 

The olfactory mucosa is discussed further on in relation to the delivery of drugs via the nose to the brain. 

Certain other substances (tetanus toxin) reach nerve cells directly via distal axonal entry. Tetanus toxin is transported to the spinal anterior horn cell, subsequently translocates and binds to presynaptic inhibitory (glycinergic) nerve terminals impinging on the motor nerve cell, and thereby suppresses the inhibition of motor neuron activity leading to hyperexcitation. Violent and sustained muscle contraction (tetany) results in response to external stimulation. Another example of peripheral entry to the CNS is the transport and delivery of metals (manganese, aluminum) from the nose along olfactory neurons to the brain of laboratory animals. 

Another delivery option for bypassing the BBB is through intranasal (IN) administration. Compared to intracerebral and intrathecal administration, IN administration is a noninvasive means of delivery of therapeutic agents to the CNS.21 22 Because of the unique connection between the nose and the brain, the olfactory neural pathway provides a route of delivery for various compounds into the CNS. These include toxic agents such as pathogens, viruses, and toxic metals. However, the same pathway can also be used to delivery various therapeutic agents including small molecules and proteins to the CNS (for review, see Refs. 21 and 23). 

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