Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain

Abstract

Background The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. Comparison with Existing Methods We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime (3H-2-PAM) to the brain of rats. Results We found that using upright vs. supine posture did not significantly affect 3H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. Conclusion In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats.

Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease

“…The rats were kept in the supine position for 2 min after administration of the dose. All experiments were carried out at 20 ± 5 °C (Krishnan 2017 ).…”

Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa

“…Possibly, this may hint that the distribution to the CNS does not include drainage to the CSF or is rapidly cleared from the CSF [47][48][49]. Further studies are necessary to elucidate the involvement of the CSF, but also of the glymphatic system [50][51][52][53]. It should be noted that CSF samples were also analyzed from the mice in study 3 by ELISA, but no significant amounts of 11C7, IC, or 11C7 scFv could be determined.…”

Advances in intranasal application of stem cells in the treatment of central nervous system diseases

“…Even in the same animal model, intranasal injection shows different delivery efficacy according to animal age and weight. Krishnan et al injected the drug radiolabeled pralidoxime into the nasal cavity of model animals, which showed that compared with younger animals with lower body weight, older animals with higher body weight required a higher dose to reach the same drug concentration in the whole brain [ 77 ]. This suggested that the distribution of intranasally administered stem cells might be affected by the age and body weight of model animals.…”