On the stability of characteristics of cellulose diacetate solutions with an iodine-containing radiopaque substance and solid emboli on their basis

Objectives. Among the materials used for embolization, liquid embolizing agents based on solutions of biocompatible polymers attract particular interest. Such compositions are capable of targeting and reliably occluding a branched vascular network by forming solid emboli directly in the patient’s body. The safety and effectiveness of such materials are determined by the stability of the initial composition and the resulting emboli. This article presents a long-term study of the stability of embolizing solutions of a polymer (cellulose diacetate) and a radiopaque additive iohexol in dimethyl sulfoxide, as well as emboli based thereon, in aqueous media. Methods. The stability of the initial solutions exposed to 60°C for 45 days (“accelerated aging” corresponding to three years of storage at 23 ± 2°C) was studied by rotational viscometry using a Brookfield DV2T RV rotary viscometer equipped with a working unit in the form of two coaxial cylinders and by ultraviolet-visible spectrophotometry using a Cary 60 UV-Vis spectrophotometer. The long-term stability of emboli in aqueous media was studied by gel permeation chromatography using a Gilson chromatograph (Japan) with refractometric detection and by gas chromatography using an Agilent 6890N chromatograph with a DB-5MS column (30 × 0.25 × 0.5 μm), equipped with an Agilent 5973 N mass spectrometric detector. Results. During “accelerated” storage of cellulose diacetate and iohexol solutions in the dark, no changes in the viscosity coefficient (0.268 ± 0.0049 Pa∙s at 25°C) and the quantitative content of bound iodine (50.1 ± 1.0 mg/mL) were observed. However, when iohexol solutions in dimethyl sulfoxide were stored under daylight, free iodine was separated in minor quantities. When emboli consisting of cellulose diacetate were stored in an aqueous medium for eight years, the molecular weight of the polymer (60 kDa) remained unchanged. The degradation products of cellulose diacetate, expected in the aqueous extract, were also absent. Conclusions. The model embolic composition consisting of cellulose diacetate and iohexol in dimethyl sulfoxide is stable when stored in the absence of light. The as-formed solid emboli remain stable for at least eight years when stored in an aqueous environment.