In Vivo Distribution of Liposome‐Encapsulated Hemoglobin Determined by Positron Emission Tomography

Abstract

Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [(15)O]H(2)O imaging, distribution of (18)F-labeled LEH in the region was gradually increased during 60-min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real-time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution.

Liposome-Encapsulated Hemoglobin Ameliorates Impairment of Fear Memory and Hippocampal Dysfunction After Cerebral Ischemia in Rats

“…5a). However, a previous study using MCAO model rats showed that LEH carries oxygen into the other ischemic regions (59). This discrepancy might be due to the differences in the types of models between them.…”

“…LEH elevates the plasma oxygen content in rats (6). However, by using positron emission tomography, an LEH analog was observed in the cerebral cortex but not in the ischemic core of the rats with MCAO caused by PIT (10). Thus, both confirmation that LEH delivers oxygen to the infarction area and determination of the mechanisms that support the protective effects of LEH against brain ischemia are required.…”

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…Several studies reported in the literature suggest the efficacy of Hb liposomes in the treatment of stroke by enhancing the biodistribution of Hb liposomes within the ischemic area in the brain. 144,145,147,[160][161][162][163][164]167,171,191,193,194 In the same way, liposomes for the delivery of angiogenic peptides 140 and VEGF 157 to promote angiogenesis in ischemic tissue were developed, and both formulations effectively promoted vascular regeneration. 140,157 Over the years, many liposomal formulations have been developed for the treatment of stroke.…”

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

“…72) In the case of LEH having a diameter of 230 nm, it was possible that the liposomes flowed to the vessels beyond the occlusion site, since LEH was small enough to pass through the occlusion. On the other hand, since it is known Size-dependent accumulation of PEG-liposomes in the ischemic region of t-MCAO rats.…”