| Temozolomide (TMZ) is one of the most effective chemical remedy in curing glioma cells. But TMZ is prone to decompose, its half life in body environment is1.24hours. Nano-hydroxyapatite (nHA) is an important inorganic biomaterials with high absorbability for medicine and excellent biocompatibility, which is perspective to be used as a carrier to prolong medicine’s clinical duration. The preparation technology of TMZ controlled release microspheres with Poly (lactic-glycolic acid)(PLGA) biodegradable polymer and nano-hydroxyapatite (nHA) crystals (abbreviated PLGA/nHA/TMZ microspheres), the releasing capability of TMZ in microspheres and cell toxicity were studied.The nHA crystals with rod-like and spherical-like morphology were prepared by wet chemical process at first, and then mixed with TMZ in order to make TMZ adsorbed on the surface of nHA nanoparticles. Taking PLGA as the microspheres material, CH2Cl2as Organic phase, PVA as water phase, Solid/Organic/Water emulsion solvent evaporation method was employed to prepare PLGA/nHA/TMZ microspheres. The effects of nHA morphology and the amount on the preparation parameters of microspheres shape, diameter, enveloped ratio, harvest ratio, drug loading were investigated. It has been shown that more wrinkling morphologies appeared and the average microparticles diameter decreased with the increasing of the nHA/TMZ amount. Compared with the TMZ laden PLGA microspheres (PLGA/TMZ), the introduction of nHA component was proven capable of largely enhancing drug encapsulation efficiency.The in vitro release of TMZ loaded microspheres was measured in phosphate buffered saline (PBS, pH7.4) at temperature of37℃. It is revealed that the release rate of TMZ from microspheres was proportional to its loading amount. The duration of TMZ release completely was almost35days.An initial burst appeared in the first day, with increased with the rise of TMZ loading amount. Compared with PLGA/TMZ, the releasing effect of PLGA/nHA/TMZ is more obvious. In the first stage, the higher content of PLGA in the PLGA/nHA/TMZ microspheres, the higher release rate of TMZ. In the last stage, the higher content of nHA in the PLGA/nHA/TMZ microspheres, the higher release rate of TMZ. The more smooth and regular the microspheres surface is, the slower release rate of TMZ. The kinetic equation and Higuchi equation was used to fit the data from the release of microspheres, and the drug release processes were also discussed.The influence of PLGA/TMZ and PLGA/nHA/TMZ microspheres on the U87cell was evaluated by MTT method. The results indicated that both the two microspheres have an significant effect on U87cell proliferation, the inhabitation rate exhibits a remarked concentration and time dependence. The inhibitory effect of PLGA/nHA/TMZ microspheres is more obvious.Compared with the rod-like nHA, the absorption capacity of spherical nHA was stronger. And the drug loading of microspheres prepared by spherical nHA was higher. In the last stage, the release rate was higher.The photograph of the cells cultured with the microspheres demonstrated that the U87cell morphology changed greatly. |
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