目的 制備地塞米松脂質體，探討地塞米松對乳腺癌4T1細胞的生長抑制作用及對荷瘤鼠的抗腫瘤藥效。方法 采用薄膜分散-超聲法，以粒徑和多分散指數（PDI）為指標進行單因素實驗考察了大豆磷脂（SPC）與甲氧基聚乙二醇磷脂（DSPE-mPEG2000）的質量比、SPC與地塞米松的質量比、超聲時間對地塞米松脂質體粒徑的影響從而篩選得到最佳處方和最佳工藝條件。采用MTT法比較地塞米松注射液和地塞米松脂質體對4T1細胞的作用。建立4T1 BAL B/c荷瘤小鼠模型，研究地塞米松脂質體對4T1荷瘤小鼠的體內抗腫瘤作用。結果 當SPC與DSPE-mPEG2000質量比為5：1、SPC與地塞米松質量比為50：3、超聲時間為20 min時制備得到的脂質體粒徑最小，粒徑分布最窄，室溫放置15 d穩(wěn)定，于生理介質中穩(wěn)定。MTT測定結果顯示地塞米松注射液和脂質體對4T1細胞生長抑制作用均較弱，但在4T1荷瘤鼠的體內實驗中，在5 mg/kg的給藥劑量下，地塞米松脂質體的抑瘤率卻高達78.9%，顯著高于地塞米松注射液（33.4%，P<0.05）和8 mg/kg紫杉醇注射液（55%，P<0.05）。結論 制備的地塞米松脂質體放置于生理介質中均能穩(wěn)定存在，能口服能靜脈給藥。地塞米松脂質體對4T1荷瘤小鼠腫瘤生長有較強的抑制作用，但體外對4T1細胞抑制抑制作用并不強，推測地塞米松脂質體是通過調節(jié)腫瘤微環(huán)境來抑制腫瘤生長。

Objective To prepare long-circulating dexamethasone liposomes and investigate its inhibitory effect on the growth of breast cancer 4T1 cells and its anti-tumor effect on tumor-bearing mice. Methods The film dispersion-ultrasonic method was used to conduct single-factor experiments with particle size and polydispersity index (PDI) as indicators to investigate the effect of mass ratio of SPC to DSPE-mPEG2000, mass ratio of SPC to dexamethasone and ultrasound time on particle size to screen for the best prescription and the best process conditions. The effects of dexamethasone injection and dexamethasone liposomes on 4T1 cells were compared by MTT assay. 4T1 BAL B/c tumor-bearing mice model was established and the anti-tumor effect of dexamethasone liposome on 4T1 tumor-bearing mice in vivo was studied. Results When the mass ratio of SPC to DSPE-mPEG2000 was 5:1, the mass ratio of SPC to dexamethasone was 50:3, and the ultrasonic time was 20 min, dexamethasone liposome had the smallest particle size and the narrowest particle size distribution, stable at room temperature for 15 d and stable in physiological medium. MTT data showed that both dexamethasone injection and dexamethasone liposome had a weak inhibitory effect on the growth of 4T1 cells, but the inhibition rate of dexamethasone liposome was 78.9% at 5 mg/kg dosage in vivo, significantly higher than that of dexamethasone injection (33.4%, P < 0.05) and Paclitaxel injection at 8 mg/kg (55%, P < 0.05). Conclusion Dexamethasone liposome can exist stably in physiological medium and can be administered orally and intravenously. Dexamethasone liposome have a strong inhibitory effect on the tumor growth of 4T1 tumor-bearing mice, but the inhibitory effect on 4T1 cells is not strong in vitro. It is speculated that dexamethasone liposome inhibit the growth of tumors by regulating the microenvironment of tumors rather than killing them directly.

R285.5

國家自然科學基金–廣東聯合基金資助項目（U1401223）