Blood Circulation and Tissue Biodistribution of Lipid−Quantum Dot (L-QD) Hybrid Vesicles Intravenously Administered in Mice

Abstract

The present work describes the pharmacokinetics of recently developed liposome-quantum dot (L-QD) hybrid vesicles in nude mice following systemic administration. Hydrophobic QD were incorporated into different bilayer compositions, and the serum stability of such hybrid vesicles was evaluated using turbidity and carboxyfluorescein release measurements. L-QD hybrid blood profile and organ biodistribution were also determined by elemental (cadmium) analysis. Following intravenous administration, different tissue biodistribution profiles and tissue affinities were observed depending on the L-QD lipid bilayer characteristics. Immediate blood clearance was observed with cationic (DOTAP/DOPE/Chol) hybrid with rapid lung accumulation, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. Overall, the L-QD hybrid vesicle system is considered a viable platform that allows QD delivery to different tissues through facile modulation of the hybrid vesicle characteristics. In addition, L-QD offers many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.

In vivo biodistribution studies and ex vivo lymph node imaging using heavy metal-free quantum dots

“…The indium (In) ion content was quantified with inductively coupled plasma-mass spectroscopy (ICP-MS) (PerkinElmer SCIEX ICP mass spectrometer, ELAN DRC 6100, USA) to determine the total indium in the organs. For all ICP-MS measurements, nitric acid blank, blank tissue samples, spiked samples with known QDs for calibration and indium standards were prepared and tested concurrently with test samples [59]. The tissues from the control rats without QD administration were dissolved in a similar manner.…”

PEGylated Inorganic Nanoparticles

“…[120] Reduced organ uptake, longer circulation time in blood, and slow accumulation of QDs in tumors have been reported for PEG-QDs. [113,[121][122][123][124] The size of the PEG molecule also influences the blood circulating time and biodistribution of the QDs. Lower molecular weight PEG-QDs showed a circulating life time of 12 min or less whereas higher molecular weight PEG-QDs had reduced macrophage recognition, much longer circulating lifetime, and showed reduced uptake by the lymph nodes and liver.…”

Nanosized Drug Delivery Vectors and the Reticuloendothelial System

“…At a 1:1 ratio of cationic lipid: uncharged lipid, however, uptake of liposomes via the lungs is increased by almost an order of magnitude, but again, accumulation in the liver and spleen does not change. The reason for this lung specific accumulation is not clear although a similar pattern of biodistribution has been observed with several cationic nanoparticles, where most of the injected dose is recovered in the lungs, with accumulation in the liver being the second most common fate of particles 10 min after initial IV administration (Al Jamal et al 2009). …”