Enhanced Delivery of Octreotide to the Brain via Transnasal Iontophoretic Administration

• Published in: Journal of drug targeting Vol. 12; no. 5; pp. 273 - 280
• Main Authors: Lerner, Eduard N., van Zanten, Elske H., Stewart, Gregory R.
• Format: Journal Article
• Language: English
• Published: Abington Informa UK Ltd 01.06.2004; Taylor & Francis
• Subjects: Administration, Intranasal; Animals; Biological and medical sciences; Blood-brain barrier; Brain - metabolism; Drug Delivery Systems; Electrotransport; Female; General pharmacology; Iontophoresis; Male; Medical sciences; Octreotide - administration & dosage; Octreotide - pharmacokinetics; Olfactory; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rabbit; Rabbits; Delivery system; Electrotransport; Pharmaceutical technology; Olfactory; Peptide hormone; Rabbit; Octreotide; Lagomorpha; Blood brain barrier; Encephalon; Vertebrata; Mammalia; Blood-brain barrier; Analog; Animal; Somatostatin
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/10611860400000938

Transnasal drug delivery affords an opportunity to circumvent the blood-brain barrier and gain direct access to the brain. To date, this approach has used a relatively passive process relying on drug instillation high into the nasal cavity, formulation and gravity for drug delivery. The present study examined the use of an applied electrical field (transnasal iontophoresis or electrotransport) to actively drive a charged peptide, octreotide, into the rabbit brain. A simply designed electrode containing a reservoir of octreotide was placed deep into the nasal cavity on both sides. A return electrode was applied to the back of the head and a current strength of 3.0 mA was applied for 60 min. In control rabbits, electrodes were placed into the nasal cavity, but no current was applied (passive delivery). Additional control animals were given a bolus intra-arterial injection of octreotide. At the conclusion of drug delivery, animals were sacrificed and samples of brain, spinal cord, cerebrospinal fluid (CSF) and plasma were taken for measurement of octreotide levels by radioimmunoassay (RIA). In a second experiment, rabbits were exsanguinated prior to drug delivery to measure the ability of iontophoresis to transport octreotide into the brain in the absence of blood or CSF circulation. In both experiments, transnasal iontophoresis resulted in significantly elevated levels of octreotide in the brain, although results varied considerably due to electrode and tissue damage related to problems with electrode insertion into the rabbit's nasal cavity. Octreotide was present in samples extending from the olfactory bulb to the cerebellum with 2- to 13-fold increases in active compared to control/passive animals. High and sustained levels of octreotide were also present in the blood following transnasal delivery, but there were negligible amounts of octreotide in the brain following systemic administration indicating that the blood was not a significant route for drug redistribution. The results demonstrate that transnasal electrotransport is a unique, minimally invasive approach for enhancing drug delivery to the brain.