To deliver drug locally and relieve the syndrome of pain after uterine artery embolization, N-[tris (hydroxymethyl) methyl] acrylamide-gelatin microspheres were prepared based on inverse suspension polymerization and then separated into a number of subgroups (150-350, 350-560, 560-710, 710-1,000, and 1,000-1,430 μm) by wet-sieving. The microspheres were dried by lyophilization or by washing with anhydrous ethanol. And ketoprofen was loaded by soaking dried blank microspheres into concentrated ketoprofen ethanol solution. The ketoprofen loading level in different subgroups of microspheres was measured and found higher when the microspheres were dried by lyophilization. Equilibrium water content and mean diameters of microspheres decreased after drug loading, especially in subgroups with larger size. The microspheres went through the catheter without any difficulty. Compression and relaxation tests were performed on microspheres before lyophilization, embosphere™, microspheres after lyophilization and ketoprofen loading microspheres. The Young's moduli were 54.74, 64.19, 98.15, and 120.44 kPa, respectively. The release of ketoprofen from microspheres in different subgroups was studied by using the USPII method and T-cell apparatus, respectively. The results indicate that the release rate of ketoprofen depends upon the diameter of microspheres, the type of dissolution apparatus and the flow rate of media in the case that T-cell apparatus was applied. The CH50 test shows that the activation of complement by ketoprofen-loaded microspheres was lower than by blank ones.
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.
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