OBJECTIVE To establish a nano sustained release drug delivery system polysuccinimide(PSI)and hydroxyapatite(HAP)with a hard core-soft coating structure and study the delivery of anti-tumor drug regorafenib.METHODS HAP and PSI were synthesize in the article.The optimal formulation and preparation process of the regorafenib-PSI-HAP was determined by single factor analysis and the box-behnken design(BBD)response surface method.The encapsulation efficiency,drug loading captivity,drug release in vitro,particle size and distribution,Zeta potential and SEM images of regorafenib-PSI-HAP were examined.RESULTS The UV spectrophotometry results showed that the maximum absorption wave of the regorafenib was at 264 nm,the stand curve was A=94.461p+0.0304,r2=0.999 8.Meanwhile,between the 2-20 μg·mL-1 of the regorafenib solutions possessed a good linear relationship at this wave.The optimal formulation prepared using MEM detected by BBD was that the concentration of rego-rafenib was 7.28 mg·mL-1,the mass ratio of HAP to regorafenib was 0.63,and the mass ratio of PSI to HAP was 3.93.The in vitro drug release test showed that PSI-HAP exhibited pH-sensitive drug release,the regorafenib-PSI-HAP can be released totally above pH 7 solution.The PSD was around 300 nm,and Zeta potential was between-10 and-17 mV which was similar to the human cell mem-brane.CONCLUSION The proposed drug delivery system can be integrated into non-agglomerated spherical nanoparticles of uniform size through a facile preparation process.The particles are easy to sterilize,and large-scale production may be achieved easily.The drug release of PSI-HAP is pH sensitive and stable.Both PSI and nano HAP possess the effect of anti-tumor cell proliferation which is very suitable for the delivery of anti-tumor drugs such as regorafenib in vivo.
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