Search

Yoshie Maitani,1 Yuri Nakamura,1 Masao Kon,1 Emi Sanada,1 Kae Sumiyoshi,1 Natsuki Fujine,1 Masumi Asakawa,2 Masaki Kogiso,2 Toshimi Shimizu21Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan; 2Nanotube Research Center (NTRC), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, JapanAbstract: The size and shape of intravenously injected particles can affect their biodistribution and is of importance for the development of particulated drug carrier systems. In this study, organic nanotubes (ONTs) with a carboxyl group at the surface, a length of approximately 2 µm and outer diameter of 70–90 nm, were injected intravenously into tumor-bearing mice. To use ONTs as drug carriers, the biodistribution in selected organs of ONTs postinjection was examined using irinotecan, as an entrapped water-soluble marker inside ONTs, and gadolinium-chelated ONT, as an ONT marker, and compared with that of a 3 µm fluorescently labeled spherical microparticle which was similar size to the length of ONTs. It was found that for irinotecan, its active metabolite and gadolinium-chelated ONTs were highly accumulated in the lung, but to a lower level in the liver and spleen. On the other hand, microparticles deposited less in the lung and more highly in the liver. Moreover, histologic examination showed ONTs distributed more in lung tissues in part, whereas microparticles were present in blood vessels postinjection. These preliminary results support the notion of using negatively charged ONTs as intravascular carriers to maximize accumulation in the lung whilst reducing sequestration by the liver and spleen. This finding suggested that ONTs are potential carriers for lung-targeting drug delivery.Keywords: organic nanotube, lung, biodistribution, microparticle, particle shape

Kazuo Watanabe, Makoto Kaneko, Yoshie MaitaniInstitute of Medical Chemistry, Hoshi University, Tokyo, JapanAbstract: Folate-polymer-coated liposomes were developed for targeted chemotherapy using doxorubicin (DXR) as a model drug. Folate-poly(L-lysine) (F–PLL) conjugates with a folate modification degree of 16.7 mol% on epsilon amino groups of PLL were synthesized. DXR-loaded anionic liposomes were coated with F–PLL, and the cellular association of F–PLL-coated liposomes was evaluated by flow cytometry, and confocal microscopy in human nasopharyngeal carcinoma KB cells overexpressing folate receptors (FRs), and human lung adenocarcinoma A549 cells [FR (-)]. The existence of a polymer layer on the surface of F–PLL-coated liposomes was confirmed by zeta potential analysis. The KB cellular association of F–PLL-coated liposomal DXR was increased compared with that of PLL-coated liposomes and was inhibited in the presence of free folic acid. Twofold higher cytotoxicity of F–PLL-coated liposomal DXR was observed compared with that of the PLL-coated liposomal DXR in KB cells, but not in A549 cells, suggesting the presence of FR-mediated endocytosis. These results indicated that folate-targeted liposomes were prepared successfully by coating the folate–polymer conjugate F–PLL. This novel preparation method of folate-targeted liposomes is expected to provide a powerful tool for the development of a folate-targeting drug nanodevice as coating with ligand–polymer conjugates can be applicable to many kinds of particles, as well as to lipid-based particles.Keywords: cellular association, folate-targeting, liposome, poly-L-lysine, polymer coating, tumor targeting