Drug Transporters in the Nasal Epithelium: An Overview of Strategies in Targeted Drug Delivery

Abstract

In this article, we discussed the expression of some ABC (e.g., P-glycoprortein, MRP and CFTR) and SLC (e.g., POT, DAT, OAT, OATP, OCT, EAAT2/GLT1 and GLUT) amino acid, metal and nucleoside transporters in the nasal mucosa. The localization and therapeutic targeting of these transporters are explored in detail. The wide array of transporters discovered so far in the nasal mucosa implies that a plethora of compounds can be delivered by targeting these transporters. The article concludes with a discussion of the potential challenges and delivery options for transporter-mediated drug targeting via the nasal route.

Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption

“…The nasal route may also offer a potential means to deliver drugs directly to the central nervous system while bypassing the blood-brain barrier, and several recent reviews describe the potential for drug transporters to act as chaperones to enhance the nose to brain transport of substrate drug compounds. 3–6 A more complete understanding of the mechanisms regulating drug absorption in the nasal cavity will help identify drug candidates with suitable characteristics for nasal delivery. Tremendous progress has been made in the identification and characterization of transporters influencing drug absorption and distribution in the gastrointestinal tract and in clearance of drugs via the hepatic or renal systems.…”

“…7, 8 Only a limited number of transporters have been investigated for their role in nasal drug absorption, however. 2, 6, 9–11 Previous investigations clearly demonstrated the expression of p-glycoprotein in the nasal mucosa of mice and cows and demonstrated its important role in limiting the transfer of drugs into the brain following nasal administration or limiting their transfer across excised nasal mucosal tissues. 12, 13 Investigations of uptake transporter activities have also used Western blotting and immunohistochemistry to confirm the expression of OCT2, OCTN2, LAT1, LAT2, CNT3, and ENT1 in cows.…”

Fluorescent organic cations for human OCT2 transporters screening: uptake in CHO cells stably expressing hOCT2

“…dopamine, histamine, Nmethylnicotinamide, choline) are organic cations [1][2]. These charged molecules are transported across cell epithelia by carrier-mediated transport proteins, mainly organic cation transporters (OCTs) and proton/cation antiporters (MATEs) [3][4][5][6]. These transporters play pivotal roles in the absorption, distribution and disposition of cationic drugs in various tissues.…”

“…These transporters play pivotal roles in the absorption, distribution and disposition of cationic drugs in various tissues. The OCTs are members of the solute carrier family, SLC22A [3][4]7]. The SLC22 family is sub-grouped according to substrates and based on the driving force for the cation transport mechanisms [1,[3][4].…”

“…The OCTs are members of the solute carrier family, SLC22A [3][4]7]. The SLC22 family is sub-grouped according to substrates and based on the driving force for the cation transport mechanisms [1,[3][4]. One of such subgroups, which translocate organic cations and weak bases in an electrogenic-, sodium chloride-and proton gradient-independent manner, is the SLC22A1-3 (OCT1-3).…”