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.

[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.

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).

Poly(acrylic acid) microspheres loaded with lidocaine: preparation and characterization for arterial embolization.

A new embolic agent, poly(acrylic acid) microspheres (PMs), was synthesized and the cytocompatibility was proved by mouse L929 fibroblast cells. An analgesic drug, lidocaine, was loaded on the PMs to relief pain caused by embolization. PMs and lidocaine loaded microspheres (LMs) were characterized by investigating infrared spectrum, morphology, particle size, and equilibrium water contents (EWC). A series of tests were employed to evaluate the elasticity of PMs, LMs and Embosphere™, including once compression, twice compression, and stress relaxation test. The pressures of PMs and LMs passing through a catheter were measured on line by our new designed device. Drug release was studied with T-cell apparatus. The properties of PMs and LMs were proved to be suitable for embolization. Both PMs and LMs in this study might be potential embolic agents in the future.

[Optimization and property evaluation of gelatin microspheres for embolization].

OBJECTIVE: To optimize the preparation of gelatin microspheres for embolization and to evaluate the physicochemical properties of the optimized microspheres. METHODS: The gelatin microspheres were prepared using emulsification crosslink method. The response surface methodology (RSM) was used in order to achieve gelatin microspheres with satisfactory degradable time and elasticity. The response values considered in this study were degradable time and elasticity, and the factors were the concentration of formaldehyde solution and the time of cross-linking reaction. The optimized microspheres were achieved by RSM. The properties of the optimized microspheres were investigated, including degradable time, elasticity, particle size, ratio of water absorption and the swelling ratio. RESULTS: The elasticity of the optimized microspheres was appropriate. The degradable time of the optimized microspheres was 2-3 weeks. The average diameter for dried gelatin microsphere was 377.6 µm, and for wet gelatin microsphere was 535.6 µm. The gelatin microsphere achieved the rate of water absorption balance at 20 min, and the average swelling ratio of gelatin microsphere was 41.9%. CONCLUSION: The gelatin microspheres optimized by RSM seemed to be suitable for clinical embolization according to the physicochemical properties.