Higher lung accumulation of intravenously injected organic nanotubes

Abstract

Abstract: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.

Effects of PEGylation on the physicochemical properties and in vivo distribution of organic nanotubes

“…The result of DOTA-ONT was quite similar to the lung accumulation of aforementioned poorly dispersed ONT, in which the high axial ratio morphology of ONT was accounted as one of the factors in the high lung accumulation. 21 Drug nanocarriers larger than 6 µm were widely acknowledged to be easily trapped by the lung capillaries via intravenous injection. 39,40 By the same mechanism, DOTA-ONT specifically accumulated in the lung because of its agglomeration and size increase in the blood ( Figure S2).…”

“…21 An ONT with a length of 2 µm outer diameter of 70-90 nm was found to accumulate specifically in the lung and be quickly cleared from blood circulation. 21 Although the observed size of this ONT is less than 100 nm, the carboxyl group-covered hydrophobic surface led this ONT to form large bundles and be poorly dispersed in water. Further, this ONT was biologically unstable because the ONT was decomposed into lipid at a pH of 7.4.…”

“…Further, this ONT was biologically unstable because the ONT was decomposed into lipid at a pH of 7.4. In contrast to those poorly dispersed ONTs, 21,22 we have successfully developed highly water-dispersed and biologically stable ONTs with an outer diameter less than 20 nm. 15,16,23 In our in vitro studies, these ONTs are effective as nanocarriers in terms of high loading for anticancer drugs and proteins and controlled release property, but in vivo validation is indispensable to advance the ONTs into potential drug nanocarriers.…”

Docetaxel-Loaded Lecithoid Nanoparticles with Enhanced Lung Targeting Efficiency and Reduced Systemic Toxicity: Developed by Solid Dispersion and Effervescent Techniques

“…25) Similar scenario was also reported in other groups. 26,27) Systemic Toxicity Study After the experimental rabbits were weekly intravenous administration of DTX-LN and DTX-INJ (weekly 0.66 mg/kg and 3-weekly 2 mg/kg DTX equivalence) for 9 weeks, their hematological parameters (white blood cells (WBC), lymphocyte (Lym), granulocyte (Gran), red blood cells (RBC), hemoglobin (HGB) and blood platelet count (PLT)) were analyzed and presented in Figs. 5A-C.…”

Zn-Coordinated Lipid Nanocapsules with High Physical Stability and Water-Responsive Morphological Change

“…Hydrogen bonding and metal coordination increased the physical stability of the lipid bilayers, and also triggered a morphological change from plates into nanotubes. These nanotubes have been shown to be potential drug carriers at both the cellular level and in animals 22,23 . However, encapsulation of the drug was inefficient since the cylindrical space within the nanotubes is open.…”