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Pharmaceuticals 2012, 5(10), 1092-1102; doi:10.3390/ph5101092
Article

Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

, †,* , ,  and
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 3 September 2012 / Revised: 27 September 2012 / Accepted: 9 October 2012 / Published: 15 October 2012
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
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Abstract

The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT) in solution and in methoxy poly(ethylene glycol) (MPEG)/poly(e-caprolactone) (PCL) amphiphilic block copolymers (MPEG-PCL) and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat) MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL). CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.
Keywords: intranasal brain delivery; glioma; anti-cancer drug; cell penetrating peptides; nanomicelles intranasal brain delivery; glioma; anti-cancer drug; cell penetrating peptides; nanomicelles
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Taki, H.; Kanazawa, T.; Akiyama, F.; Takashima, Y.; Okada, H. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors. Pharmaceuticals 2012, 5, 1092-1102.

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