Int J Pharm. 2021 Feb 24:120393. doi: 10.1016/j.ijpharm.2021.120393. Online ahead of print.
ABSTRACT
BACKGROUND: Iodine-131 labeled hypericin (131I-Hyp) has been utilized as a necrosis-avid theragnostic tracer in a dual targeting pan-anticancer strategy called OncoCiDia. Widespread use of previously-tested solvent dimethyl sulfoxide (DMSO) is limited by safety concerns. To tackle this, the present study was designed to explore a clinically feasible excipient for the form ulation of the hydrophobic 131I-Hyp for intravenous administration.
METHOD: Solubility of Hyp in serial solutions of already-approved hydroxypropyl-β-cyclodextrin (HP-β-CD) was evaluated by UVspectrophotometry and 50% HP-β-CD was chosen for further experiments. Two novel HP-β-CD-based formulations of 131I-Hyp were compared with previous DMSO-based formulation, with regards to necrosis-targetability and biodistribution, by magnetic resonance imaging, single-photon emission computed tomography (SPECT), gamma counting, autoradiography, fluorescence microscopy and histopathology.
RESULTS: Hyp solubility was enhanced with increasing HP-β-CD concentrations. The radiochemical purity of 131I-Hyp was higher than 90% in all formulations. The necrosis-targetability of 131I-Hyp in the novel formulations was confirmed in vivo by SPECT and in vitro by autoradiography, fluorescence microscopy and histopathology. The plasma clearance of r adioactivity was faster in the novel formulations.
CONCLUSION: The novel 131I-Hyp formulations with HP-β-CD could be a suitable pharmaceutical excipient for 131I-Hyp for intravenous administration.
PMID:33639227 | DOI:10.1016/j.ijpharm.2021.120393
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