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  • Title: Surface characteristics of holmium-loaded poly(L-lactic acid) microspheres.
    Author: Zielhuis SW, Nijsen JF, Figueiredo R, Feddes B, Vredenberg AM, van het Schip AD, Hennink WE.
    Journal: Biomaterials; 2005 Mar; 26(8):925-32. PubMed ID: 15353204.
    Abstract:
    Radioactive holmium-166-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) are promising systems for the treatment of liver malignancies. The surface characteristics of Ho-PLLA-MS before and after both neutron and gamma irradiation were investigated in order to get insight into their suspending behaviour and to identify suitable surfactants for clinical application of these systems. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) were used for surface characterization. The residual amounts of poly(vinyl alcohol) (PVA) of the microspheres, which was used as an emulsifier during the solvent evaporation process, were determined using a colorimetric iodine-borate method and the wettability of microspheres and PLLA films with and without holmium (Ho) loading was tested using suspending experiments and contact angle measurements. XPS showed that the surface of Ho-PLLA-MS mainly consisted of PLLA, less than 10% of the surface was covered with PVA after several washing and sieving steps. A colorimetric assay showed that the microspheres contained 0.2-0.3% (w/w) PVA. Combined with XPS data, this assay demonstrates that the PVA is likely dissolved in the core of the microspheres. XPS analysis also showed that after neutron irradiation, some holmium appeared on the surface. Moreover, Ho-loaded PLLA films had a much higher contact angle (85 degrees) than non-loaded films (70 degrees). Therefore, the Ho on the surface of neutron-irradiated Ho-PLLA-MS is probably the reason for their poor suspending behaviour in saline. No surface changes were seen with XPS after gamma irradiation. Based on their surface characteristics, a pharmaceutically acceptable solvent (1% Pluronic F68 or F127 in 10% ethanol) was formulated with which a homogeneous suspension of radioactive Ho-PLLA-MS could be easily obtained, making these systems feasible for further clinical evaluation.
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