Sodium cholate, a solubilizing agent for the necrosis avid radioiodinated hypericin in rabbits with acute myocardial infarction

Abstract

(2015) Sodium cholate, a solubilizing agent for the necrosis avid radioiodinated hypericin in rabbits with acute myocardial infarction, Drug Delivery, 22:3, 427-435, DOI: 10.3109/10717544.2013 I-Hyp) and investigated biodistribution and targetability of this formulation in rabbits with acute myocardial infarction (AMI). Materials and methods: Solubility of radioiodinated hypericin/hypericin (Hyp) in NaCh solutions was evaluated by microscopy. Hyp with 123 I-sodium iodide was performed using hydrogen peroxide as oxidant in 0.06 M NaCh. Radiochemical yield determination and purification were conducted using high performance liquid chromatography.123 I-Hyp was solubilized in 0.06 M NaCh containing 1.9 Â 10 À4 M Hyp. The formulation was macroscopically inspected and intravenously injected to five rabbits with AMI. At 24 h, biodistribution was evaluated by tissue gamma counting (TGC) and necrosis targetability was assessed by TGC, autoradiography, fluorescence examination and histology. Results: Microscopically NaCh at 0.06 M shows the best properties for solubilizing the radioiodinated Hyp/Hyp. 123I-Hyp in 0.06 M NaCh was achieved in 85% with radiochemical purity of 99% after purification. NaCh-dissolved 123 I-Hyp/Hyp shows no particles. By TGC, animals exhibited higher (p ¼ 0.003) radioactivity accumulation in AMI (0.8 ± 0.2% ID/g) than in normal myocardium (0.05 ± 0.02% ID/g), as confirmed by autoradiography, fluorescence measurement and histology. Among organs, the highest uptake of radioactivity was found in liver (15.7 ± 0.6% ID), large (9.7 ± 1.0% ID) and small (5.9 ± 0.6% ID) intestines. Conclusion: Necrosis avidity of NaCh-dissolved 123 I-Hyp/Hyp and its hepatobiliary excretion were demonstrated. The suitability of NaCh as solubilizing agent of 123 I-Hyp for hotspot imaging of AMI was proved.

A novel multimodal nanoplatform for targeting tumor necrosis

“…10 In order to improve hypericin biodistribution for use in necrosis affinity, a variety of delivery methods have been used in previous studies, including solubilizing in organic solvents such as DMSO, or admixture with PEG 400, propylene glycol, and sodium cholate. 26,27 We incorporated a biodegradable PEG-PCL polymer shell to produce a highly biocompatible and soluble nanoplatform encapsulating gold nanoparticles and hypericin. PEG-PCL involves di-block copolymers with both hydrophilic and hydrophobic components capable of generating watersoluble nanoparticles with a hydrophobic core and hydrophilic shell in aqueous solutions.…”

Updated developments on molecular imaging and therapeutic strategies directed against necrosis

“…Despite the substantial translational potential related to certain oncological and non-oncological applications 66 , some inherent defects such as extremely poor water solubility, easy to form aggregates and deep colors may haunt its further clinical transformation. Except that the formulation approach had been used to solubilize Hyp173., 174., 175., structural modifications had also been attempted to solve the problems confronted. It was reported that the distortion of the π systems or reducing the size of π -conjugated core not only could improve aqueous solubility of molecules176., 177., but also could decrease or even prevent the aggregation of molecules130., 134..…”

Avenues to molecular imaging of dying cells: Focus on cancer

“…462 Formation of aggregates should be avoided by addition of PEG400 or sodium cholate. [463][464][465][466] Various hypericin analogs with better solubility have been proposed. 454,[467][468][469] Uptake mechanism is poorly defined.…”