[Preparation and investigation of MRI-traceable Eudragit-E liquid embolic agent].

OBJECTIVE: To develop and investigate the properties of MRI-traceable Eudragit-E liquid embolic agent (MR-E). METHODS: Polyethylene glycol-modified superparamagnetic iron oxides (PEG-SPIO) was synthesized by chemical co-precipitation method. MR-E was prepared by mixing PEG-SPIO and Eudragit-E liquid embolic agent homogeneously. An in vitro MR phantom study was carried out to measure MR traceability of MR-E and to determine the concentration of PEG-SPIO for further studies. The microcatheter deliverability and sol-gel transition process of MR-E were investigated. MR-E was injected into the kidney of a Japanese white big ear rabbit via an angiographic microcatheter, and detected by MRI. RESULTS: A PEG-SPIO concentration of 2 g/L was considered to be suitable for further studies. MR-E was injected through the microcatheter without any difficulty. MR-E instantly solidified on release into saline. Then 0.2 mL of MR-E effectively embolized distal renal arteries, and MR-E could be detected by MRI in the embolized kidney. CONCLUSION: MR-E seems to be a promising MRI-traceable liquid embolic agent.

[Preparation and property study of doxorubicin loaded microspheres].

OBJECTIVE: To prepare doxorubicin-loaded polyvinylalcohol-acrylic acid (PVA-AA) microspheres and evaluate properties of this chemoembolic agent. METHODS: PVA-AA microspheres were synthesized by inverse suspension polymerization method and then verified by infrared spectroscopy. drug loading (DL) and entrapment efficiency (EE%) were measured after doxorubicinwas loaded on PVA-AA microspheres. Their morphology and elasticity were investigated by optical microscope, environmental scanning electron microscope and texture analyzer, respectively. T-cell apparatus was used to evaluate the in vitro release behavior of doxorubicin-loaded microspheres.The external carotid of the rabbit was chosen as an embolization site to evaluate the in vivo embolic property of the microspheres. RESULTS: PVA-AA microspheres, which were transparent spheres,turned into red spheres after doxorubicin loading. DL of the microspheres was (20.56 ± 0.69)g/L and (23.25 ± 0.27) g/L,and EE% was 82.22% ± 2.76% and 93.00% ± 1.06% within 20 min and 6 h, respectively. The in vitro release results showed a significantly delayed release of the drug for 10.32% ± 0.47% after 24 h. The Young's modulus was (178.30 ± 12.33) kPa and (213.29 ± 15.61) kPa for blank microspheres and doxorubicin-loaded microspheres, respectively. Both blank microspheres and doxorubicin-loaded microspheres exhibited good elasticity. In vivo embolization showed that 0.3 mL of microspheres could produce distal embolic efficiency. CONCLUSION: The doxorubicin-loaded microspheres are expected to be a promising new chemoembolic agent.

MRI Detectable Polymer Microspheres Embedded With Magnetic Ferrite Nanoclusters For Embolization: In Vitro And In Vivo Evaluation.

OBJECTIVE: The objective of this study was to develop magnetic embolic microspheres that could be visualized by clinical magnetic resonance imaging (MRI) scanners aiming to improve the efficiency and safety of embolotherapy. METHODS AND DISCUSSION: Magnetic ferrite nanoclusters (FNs) were synthesized with microwave-assisted solvothermal method, and their morphology, particle size, crystalline structure, magnetic properties as well as T2 relaxivity were characterized to confirm the feasibility of FNs as an MRI probe. Magnetic polymer microspheres (FNMs) were then produced by inverse suspension polymerization with FNs embedded inside. The physicochemical and mechanical properties (including morphology, particle size, infrared spectra, elasticity, etc.) of FNMs were investigated, and the magnetic properties and MRI detectable properties of FNMs were also assayed by vibrating sample magnetometer and MRI scanners. Favorable biocompatibility and long-term MRI detectability of FNMs were then studied in mice by subcutaneous injection. FNMs were further used to embolize rabbits' kidneys to evaluate the embolic property and detectability by MRI. CONCLUSION: FNMs could serve as a promising MRI-visualized embolic material for embolotherapy in the future.

Poly(acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization and MRI detectability: In vitro and in vivo evaluation.

To develop embolic microspheres with MRI detectability, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized and mixed with monomer of acrylic acid to prepare SPIONs-loaded polymerized microspheres (SPMs) by inverse suspension polymerization method. The SPMs were evaluated for the ability of embolization by investigating the morphology, particle size, elasticity and renal arterial embolization to rabbits. Meanwhile, the loading of SPIONs was verified by optical microscope, transmission electron microscope, Fourier transform infrared spectrum, vibrating sample magnetometer, X-ray diffraction and X-ray photoelectron spectroscopy, and the content of SPIONs in SPMs was measured quantitatively. Furthermore, the MRI detectability of SPMs was testified in gel phantom, mice and rabbits respectively by a clinical 3.0T MRI scanner. The results revealed the SPMs were potential MRI detectable embolic microspheres for improving the effectiveness and safety of embolotherapy in the future.

Preparation and evaluation of biocompatible long-term radiopaque microspheres based on polyvinyl alcohol and lipiodol for embolization.

The aim of this work was to develop long-term radiopaque microspheres (LRMs) by entrapping lipiodol in biocompatible polyvinyl alcohol with multiple emulsions chemical crosslinking method. The high content of lipiodol (0.366 g/mL) was hardly released from LRMs in vitro and the radiopacity could maintain at least 3 months after subcutaneous injection in mice without weakening. A series of tests was performed to evaluate the feasibility of LRMs for embolization. LRMs were proved to be smooth, spherical, and well dispersed with diameter range of 100-1200 µm. Young's modulus of LRMs was 55.39 ± 9.10 kPa and LRMs could be easily delivered through catheter without aggregating or clogging. No toxicity of LRMs was found to mouse L929 fibroblasts cells and only moderate inflammatory in surrounding tissue of mice was found after subcutaneous injection of LRMs. After LRMs were embolized in renal artery of a rabbit, the distribution and radiopacity of LRMs in vivo were easily detectable by X-ray fluoroscopy and computed tomography (CT) imaging, respectively. More accurate distribution of LRMs in embolized kidney and vessels could be detected by high-revolution visualization of micro-CT ex vivo. In conclusion, the LRMs were proved to be biocompatible and provide long-term radiopacity with good physical and mechanical properties for embolization.

Development and evaluation of liquid embolic agents based on liquid crystalline material of glyceryl monooleate.

New type of liquid embolic agents based on a liquid crystalline material of glyceryl monooleate (GMO) was developed and evaluated in this study. Ternary phase diagram of GMO, water and ethanol was constructed and three isotropic liquids (ILs, GMO:ethanol:water=49:21:30, 60:20:20 and 72:18:10 (w/w/w)) were selected as potential liquid embolic agents, which could spontaneously form viscous gel cast when contacting with water or physiological fluid. The ILs exhibited excellent microcatheter deliverability due to low viscosity, and were proved to successfully block the saline flow when performed in a device to simulate embolization in vitro. The ILs also showed good cytocompatibility on L929 mouse fibroblast cell line. The embolization of ILs to rabbit kidneys was performed successfully under monitoring of digital subtraction angiography (DSA), and embolic degree was affected by the initial formulation composition and used volume. At 5th week after embolization, DSA and computed tomography (CT) confirmed the renal arteries embolized with IL did not recanalize in follow-up period, and an obvious atrophy of the embolized kidney was observed. Therefore, the GMO-based liquid embolic agents showed feasible and effective to embolize, and potential use in clinical interventional embolization therapy.

Research of novel biocompatible radiopaque microcapsules for arterial embolization.

Embolic agents, such as microparticles, microspheres or beads used in current embolotherapy are mostly radiolucent, which means the agents are invisible under X-ray imaging during and after the process of embolization, and the fate of these particles cannot be precisely assessed. In this research, a radiopaque embolic agent was developed by encapsulating lipiodol in polyvinyl alcohol. The lipiodol-containing polyvinyl alcohol microcapsules (LPMs) were characterized and evaluated for their morphology, size distribution, lipiodol content, lipiodol release, elasticity, and deliverability through catheter. The radiopacity of LPMs in vials and in living mice was both detected by an X-ray imaging system. The biocompatibility of LPMs was investigated with L929 cells and in mice after subcutaneous injection. Embolization of LPMs to a rabbit kidney was performed under digital subtraction angiography (DSA) and the radiopacity of LPMs was verified by computed tomography (CT).