目的 制備負(fù)載鬼臼毒素聚乳酸-羥基乙酸共聚物納米粒（PPT-loaded PLGA NPs），并考察其對(duì)人乳腺癌MCF-7細(xì)胞的抗腫瘤活性。方法 采用乳化–溶劑蒸發(fā)法制備PPT-loaded PLGA NPs，以聚乳酸-羥基乙酸共聚物（PLGA）、聚乙烯醇（PVA）、D-α-維生素E聚乙二醇1000琥珀酸酯（TPGS）質(zhì)量濃度作為自變量，以粒徑分布、包封率作為因變量，采用中心復(fù)合設(shè)計(jì)–響應(yīng)面法進(jìn)行處方優(yōu)化。使用透射電鏡觀察微觀形態(tài)，采用透析法考察PPT-loaded PLGA NPs在不同pH值釋放介質(zhì)中的體外釋藥特性，考察其對(duì)人乳腺癌MCF-7細(xì)胞的抗腫瘤作用。結(jié)果 PPT-loaded PLGA NPs的最優(yōu)處方為：PLGA質(zhì)量濃度為120.0 mg/mL，PVA質(zhì)量濃度為20.0 mg/mL，TPGS質(zhì)量濃度為2.5 mg/mL。制備的PPT-loaded PLGA NPs呈規(guī)則球形結(jié)構(gòu)，實(shí)測(cè)粒徑（163.6±4.2）nm、包封率（89.4±0.6）%。PPT-loaded PLGA NPs體外釋藥速率具有緩釋性，48 h累積釋放率達(dá)90%。PPT-loaded PLGA NPs對(duì)人乳腺癌MCF-7細(xì)胞表現(xiàn)出良好的體內(nèi)外抗腫瘤活性。結(jié)論 成功制備了PPT-loaded PLGA NPs，其具有良好的緩釋效果和體內(nèi)外抗腫瘤活性。

Objective To prepare podophyllotoxin loaded PLGA nanoparticles (PPT-loaded PLGA NPs) and to evaluate the anti-tumor activity against human MCF-7 breast cancer cells. Methods PPT-loaded PLGA NPs were prepared by emulsification - solvent evaporation method. PLGA concentration, PVA concentration, and TPGS concentration were used as variable factors, particle size distribution and encapsulation rate were used as evaluation indexes, and central composite design - response surface method was used to optimize the prescription. The microscopic morphology was observed with transmission electron microscope. The in vitro release characteristics of PPT-loaded PLGA NPs in different pH value release media were investigated by dialysis method. The anti-tumor activities of PPT-loaded PLGA NPs against human MCF-7 breast cancer cells were studied. Results The optimal formulation of PPT-loaded PLGA NPs was as followed: with PLGA concentration of 120.0 mg/mL, PVA concentration of 20.0 mg/mL, and TPGS concentration of 2.5 mg/mL. PPT-Loaded PLGA NPs was distributed in a spherical shape, the average particle size was (163.6 ± 4.2) nm, and the encapsulation rate was (89.4 ± 0.6)%. The in vitro release rate of PPT-loaded PLGA NPs exhibited sustained release, with a cumulative release rate of 90% after 48 h. PPT-loaded PLGA NPs showed good antitumor activity in vitro and in vivo against human MCF-7 breast cancer cells. Conclusion PPT-loaded PLGA NPs are successfully prepared with good sustained release and anti-tumor activities in vitro and in vivo.

R282.4

湖北省衛(wèi)生健康科研項(xiàng)目（WJ2021M218）