目的 制備基于藻酸雙酯鈉的阿霉素/塞來昔布納米藥物晶體（PPDC），并考察其體外抗腫瘤作用。方法 采用納米沉淀法制得PPDC混懸液，分別表征PPDC的形態(tài)、粒徑、電位、藥物晶型、藥物包載情況、釋藥性能，通過細胞攝取、細胞毒性、細胞侵襲、細胞黏附評價PPDC對4T1細胞的抑制作用。結(jié)果 PPDC混懸液呈規(guī)則球形，分散性良好，分布較窄，載藥量高。塞來昔布、阿霉素以無定型穩(wěn)定狀態(tài)存在于PPDC中。PPDC在體外釋放72 h時攜載的藥物能夠有效釋放。體外細胞實驗表明，PPDC能被4T1細胞攝取，細胞毒作用具有濃度相關性，并顯著抑制細胞侵襲和細胞黏附。結(jié)論 PPDC有效解決塞來昔布的難溶性、穩(wěn)定劑毒性大等問題，與阿霉素共載實現(xiàn)兩藥協(xié)同抑制腫瘤細胞生長和轉(zhuǎn)移的作用。

Objective To prepare doxorubicin/celecoxib drug nanocrystals (polysaccharide sulfate/PVP/doxorubicin/celecoxib, PPDC) based on polysaccharide sulfate (PSS), and study its antitumor effect in vitro. Methods PPDC suspension was prepared by nano precipitation method. The morphology, particle size, potential, drug crystal form, drug loading, and drug release performance of PPDC were characterized, respectively. The inhibition of PPDC against 4T1 cells was evaluated by cell uptake, cytotoxicity, cell invasion, and cell adhesion. Results PPDC suspension was regular spherical, with good dispersion, narrow distribution, and high drug loading. Celecoxib and doxorubicin existed in PPDC in an amorphous and stable state. Drug loaded by PPDC can be effectively released after 72 h in vitro release. In vitro cell experiments showed that PPDC could be taken up by 4T1 cells, and its cytotoxicity was concentration dependent, significantly inhibiting cell invasion and cell adhesion. Conclusion PPDC can effectively solve the problems such as insolubility of celecoxib and high toxicity of stabilizer, and achieve the synergistic effect with doxorubicin in inhibiting growth and metastasis of tumor cells.

R944

國家自然科學基金資助項目（81803101）；天津市自然科學基金資助項目（19JCQNJC12300）