Intranasal delivery of NAD+

Intranasal delivery is the quickest, most efficient way to deliver NAD+ directly to the brain. It is the best option to bypass the blood-brain barrier, reduce systemic adverse effects of drugs, and to allow a lower dose of drugs to be administered.

Intranasal delivery bypasses the blood/brain barrier

blood brain barrier The purpose of the blood–brain barrier is to protect against toxins or pathogens circulating in the blood that might cause brain infections, while at the same time allowing vital nutrients to reach the brain.

In a study published in September 2018, administration of LABELED NAD+ by IP and IV injection demonstrated that exogenous NAD+ crosses the blood brain barrier to enter the hypothalamus INTACT, reduces hunger and weight gain, and increases energy expenditure and fat burning in mice.

The study also shows that NR and NMN can not utilize the cd43 gap to cross the blood brain barrier.

"In conclusion, our results demonstrate that exogenous NAD is effectively imported into the hypothalamus and increases hypothalamic NAD content. Therefore, NAD supplement can constitute a therapeutic method for metabolic disorders characterized by hypothalamic NAD depletion in humans."(1)

Intranasal reduces systemic adverse effects of drugs

Because intranasal delivers drugs to a targeted area, it reduces the chances for systemic adverse side effects.  Systemic side effects are defined as those effects occurring in tissues distant from the site of contact between the body and the medical device or biomaterial.

"Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs."(2)

intranasal-delivery-pathways
Intranasal Delivery - The so-called nose-to-brain pathway

prion diseases Studies in mice show that intranasally-administered NAD+ increase hippocampal NAD+ levels and reduce TBI-induced neuronal death in the hippocampus. (4) (5)

"The profound protective effects of the intranasal NAD+ administration were also observed at 72 hrs after ischemia."(3)

"intranasal administration with 10 mg / kg NAD+, but not with 5 mg / kg NAD+, significantly attenuated the ischemia / reperfusion-produced neurological deficits"(3)

Loss of blood flow due to traumatic brain injury or stroke also results in NAD+ starvation and neuronal death.

The research below shows these ailing neurons may benefit from intranasal NAD+ treatment.

"Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains."(3)

"Intranasal delivery with 10 mg / kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct"(3)

"The NAD+ administration also significantly attenuated ischemia-induced neurological deficits."(3)

"NAD+ metabolism is a new target for treating brain ischemia"(3)

"It is noteworthy that NAD+ can reduce infarct formation by up to 86 % even when administered at 2 hrs after ischemic onset."(3)

"The protective effect of NAD+ could be one of the most profound effects ever reported."(3)

"Intranasal administration with nicotinamide at 10 mg / kg can not affect ischemic brain damage, in contrast to the profound protective effects of 10 mg / kg NAD+."(3)

 

References:

  1. Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic Connexin 43 (Roh, 2018)
  2. Evaluation of intranasal delivery route of drug administration for brain targeting
  3. Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia
  4. Prevention of Traumatic Brain Injury-Induced Neuron Death by Intranasal Delivery of Nicotinamide Adenine Dinucleotide
  5. Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment