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Journal of Drug Delivery
Volume 2012, Article ID 245835, 9 pages
http://dx.doi.org/10.1155/2012/245835
Research Article

Effects of Atelocollagen Formulation Containing Oligonucleotide on Endothelial Permeability

1Formulation Research and Development Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 1-3-45 Kurakakiuchi, Ibaraki-shi, Osaka 567-0878, Japan
2Department of Pathology, Sapporo Medical University School of Medicine, S1, W17, Sapporo 060-8556, Japan
3Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka 554-0022, Japan
4Research Institute, Koken Co., Ltd., 2-13-10, Ukima, Kita-ku, Tokyo 115-0051, Japan

Received 29 August 2011; Revised 11 December 2011; Accepted 12 December 2011

Academic Editor: Rassoul Dinarvand

Copyright © 2012 Koji Hanai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.