Preparation Of Mesoporous Hydroxyapatite Nanoparticles And Application As A Controllable Release Carrier Of Drug

In recent years, the controlled drug release has been a newly arisen interdisciplinary subject. In the controlled drug release system, drugs or other active substances is combined with the good biocompatibility carriers by certain physical or chemical method. And the controlled drug release can exhibit a long-term, steady and proper release concentration in the lesion location within the required time via controlling the drug of diffusion and osmosis in the body. Comparing with the traditional pattern of drug delivery, the controlled drug release has characteristics of fewer times of usage, high stability, low toxicity, high curative effect and so on. Drug carrier is the most important part of the sustained release system because different drug carrier has different release effect. At present, there are many different kinds of drug carrier, the hydroxyapatite (HA) nanoparticles haave high surface area, large pore volume, mesoporous structure, excellent bioactivity and biocompatibility, which results in a common kind of drug carriers.Reported in the literature, there are a lot of the synthesis methods of HA nanoparticles. In this paper, HA nanoparticles and magnetic ferroferric oxide (Fe3O4)/ HA composite were synthesized via gas-liquid chemical precipitation combining with hydrothermal method. And applying the oscillation adsorption method, we have investigated the anti-cancer drug/protein adsorption on HA/Fe3O4/HA composite and the controlled release in in vitro. The main results of the studies are as follows:1. Hydroxyapatite nanoparticles were synthesized through gas-liquid chemical precipitation method at ambient temperature without any template. The prepared HA were observed and measured using the X-ray powder diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) and Barret-Joyner-Halenda scheme (BJH). The results are as follows:The prepared HA had good crystal structure, high purity, and good dispersibility; HA could form uniform nanometer sized particles, HA particles were similar to spindles which are 100-150 nm long,20 nm wide, and the surface of HA had the mesoporous of 2-10 nm; The specific surface of HA area was 116.8 m2/g, pore volume was 0.508 cm3/g. In addition, the kinetics and thermodynamics of the DOX adsorption on HA were systematically studied:the DOX adsorption on HA conformed to the Langmuir model; the DOX adsorption on HA was a pseudo-second-order kinetic process and intra-particle diffusion was a rate-limiting step; the adsorption of DOX on HA was an endothermic, increasing entropy process, spontaneous and belonged to physical adsorption. Moreover, the DOX cumulative release behaviors of the DOX-loaded HA in vitro were investigated at different pH values of phosphate buffer solution (PBS), the results showed that DOX-loaded HA exhibited a slow, long-term and steady release rate in PBS, and The release rate could be adjusted via varying the pH value of the release medium.2. Mesoporous Fe3O4/HA composite were synthesized by gas-liquid chemical precipitation method at ambient temperature, too. The prepared Fe3O4/HA composite were observed and measured using the XRD、TEM、BET、BJH、Vibrating Sample Magnetometer (VSM) and so on. Fe3O4 particles of 10-20 nm were embedded in the spindle HA particles which were 100-150 nm long,20 nm wide. The specific surface of Fe3O4/HA composite area was 124.05 m2/g, pore volume was 0.42 cm3/g, the saturation magnetization were 16.20 emu/g; and the DOX-loaded Fe3O4/HA composite had magnetic properties, too. Furthermore, the DOX cumulative release behaviors of the DOX-loaded Fe3O4/HA in vitro were investigated at different pH values of PBS, the release rate could be adjusted by varying the pH value of the release medium. The DOX cumulative release rate was about 20%, so the DOX-loaded Fe3O4/HA composite could avoid burst effect. And the DOX-loaded Fe3O4/HA composite could release drug at a long-term, steady, and safe rate in the next 100 h. Consequently, Fe3O4/HA-DOX system had the characteristics of magnetic targeting drug delivery system which could realize drug targeting delivery, reduce dosing frequency and relieve the pain of cancer patients.3. Mesoporous HA nanoparticles were synthesized by gas-liquid chemical precipitation combining with hydrothermal method, and the prepared HA were observed and measured using the XRD、TEM、BE、BJH、Fourier transform infrared spectrophotometer (FTIR) and so on. The analysis results are as follows:the prepared HA had good crystal structure, high purity, very good dispersibility. HA particles were similar to rods which were 100-150 nm long,40 nm wide. The specific surface of Fe3O4/HA composite area was 87.3 m2/g, pore volume was 0.338 cm3/g. The adsorption isotherms of bovine serum albumin (BSA) on as-prepared HA at various temperatures were observed, and the BSA maximum loading capacity on HA could reach 140 μg/mg. To analyze the adsorption model, the isothermal adsorption data were simulated by different common adsorption models in the literature, the result showed that the BSA adsorption on HA belonged to the Langmuir model. In addition, the BSA cumulative release behaviors of the BSA-loaded HA in vitro were investigated at different pH values of PBS. The release rate was different at different pH values due to the effect of charge repulsion. Furthermore, the vitro release was in accordance with the Korsmeyer-Peppas equation and the release mechanism fitted the non-Fickian diffusion. The BSA-loaded HA composite could not only avoid burst effect but also release drug at a long-term, steady, and safe rate.