Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

“…However, nelfinavir may still have direct access to the brain and CNS through the olfactory nerves connecting the olfactory bulb and the brain. This drug penetration process was demonstrated with morphine (11). Several other studies have shown that intranasally delivered P-glycoprotein substrates GF120918, rifampin, and verapamil can still result in improved brain concentrations (12,38).…”

“…In contrast, the nose drops at the volumes used in this study (<30 μl) deposited at of the respiratory region. Our preliminary studies with 7-and 15-mm catheters for deposition to the olfactory region also showed much lower fraction of drug deposited at the olfactory region [even though this method has been used in many studies with the objective of targeting the olfactory region (11,(25)(26)(27)]. With catheter administration, the dye was localized to the distance that the catheter was inserted, but the dye did not penetrate the tight spaces between the nasal septum and the turbinates of the olfactory region well (data not shown).…”

“…Many nose-to-brain drug delivery studies have described high concentrations of drug appearing in and around the olfactory bulb within minutes after drug administration (6)(7)(8). In addition, several drugs have been visualized crossing these fluid pathways in the cribriform plate region from the nasal cavity to the CNS (9)(10)(11).…”

“…A variety of nasal delivery methods are typically used in studies investigating nose-tobrain delivery in rodents, but very few studies specifically and consistently deposit drug on the olfactory epithelium. The most commonly used nasal administration modes are nose drops (18)(19)(20)(21), in which the animal is placed on its back in a supine position while liquid drops are snorted into the nasal cavity, or inserting a soft catheter connected to a microsyringe into the nasal cavity and applying a volume of drug a set distance into the nasal cavity from the naris (11,22). These methods may effectively deliver drug to the nasal cavity; however, they tend to involve a large dose volume resulting in saturation of both the respiratory and olfactory epithelium.…”

Characteristics of Olfactory Epithelium and Manipulations of Neural Functions in the Brain by the Intranasal Administration

“…154 L-DOPA 17,19) 197 meptazinol 9) 233 lidocaine 10) 234 estradiol 37) 272 morphine 38) 285 testosterone 39) 288 cocaine 19) 303 a‰atoxin B 40,41) 312 progesterone 18) 314 pregnenolone 42) 316 GW468816 10) 380 GR138950 10) 405 GV196771 10) 412 GR138950 8) 493 Mouse GABA 103 dopamine 8) 154 rotenone 394 Gilt androstenol 43) 274 Molecules (high MW) Rat orexin-A 44) 3561 human b-amyloid 27) 4615 IGF-I 21,45) 7649 leptin 22,46) 16000 interferon-b 47) 22500 Mouse human b-amyloid 4615 NGF 48) 13000 leptin 16000 anti-Glu antibody 26) anti-GABA antibody 26) Monkey orexin-A 28) 3561 interferon-b 49) 22500 Human orexin-A 31) 3561 vasopressin 29) 1056 insulin 33 35) 5808 melanocortin (MSH) 30 …”