目的 構(gòu)建半乳糖修飾的pH敏感型青蒿琥酯納米囊泡（Gal-Art-NVs），考察其體內(nèi)組織分布及抗腫瘤作用。方法 采用乙醇注入法制備Gal-Art-NVs。以包封率、載藥量、粒徑為指標(biāo)，通過單因素實(shí)驗(yàn)結(jié)合Box-Behnken響應(yīng)面法優(yōu)化Gal-ArtNVs處方工藝，并將其制備成凍干粉。透射電鏡觀察Gal-Art-NVs微觀形態(tài)，體外透析法考察其在pH 5.0、5.5、6.5、7.4磷酸鹽緩沖液中的釋藥行為。建立肝癌大鼠模型，采用尾iv給藥，測(cè)定不同時(shí)間點(diǎn)青蒿琥酯注射液和Gal-Art-NVs在各組織中的藥物質(zhì)量濃度，計(jì)算相對(duì)攝取率（RUE）和峰濃度比值（Ce），評(píng)價(jià)該給藥系統(tǒng)的體內(nèi)靶向性；同時(shí)計(jì)算抑瘤率以評(píng)價(jià)Gal-Art-NVs的體內(nèi)抗腫瘤效果。結(jié)果 Gal-Art-NVs最佳處方為：青蒿琥酯質(zhì)量濃度為0.98 mg·mL^-1，失水山梨醇單油酸酯與膽固醇琥珀酸單酯用量比為1.93∶ 1.00，囊材與青蒿琥酯用量比為20.77∶ 1.00，半乳糖硬脂酸酯用量為囊材總質(zhì)量的8%。優(yōu)化后Gal-ArtNVs平均包封率為（85.68± 1.07）%，載藥量為（3.91± 0.14）%，粒徑為（183.76± 7.60） nm，ζ電位為（-26.79±1.04） mV，呈橢圓形囊泡狀。該納米囊泡在pH 5.0、5.5磷酸鹽緩沖液中可顯著提高青蒿琥酯的釋藥速率及累積釋放率，表現(xiàn)出明顯的pH敏感性。與青蒿琥酯注射液相比，Gal-Art-NVs在腫瘤組織的RUE和Ce分別增至3.02倍和1.95倍；與模型組相比，GalArt-NVs可顯著抑制荷瘤裸鼠的腫瘤生長，Gal-Art-NVs組（30 mg·kg^-1）抑瘤率達(dá)64.21%。結(jié)論 Gal-Art-NVs具有pH敏感性，能增加青蒿琥酯在腫瘤部位蓄積，從而有效提高其抗腫瘤藥效。

Objective To construct galactose-modified pH-sensitive artesunate nanovesicles (Gal-Art-NVs) and investigate their in vivo tissue distribution and anti-tumor efficacy. Methods Gal-Art-NVs were prepared by the ethanol injection method. The formulation process was optimized based on the encapsulation efficiency, drug loading, and particle size through single-factor experiments combined with the Box-Behnken response surface method, and then freeze-dried. The microscopic morphology of GalArt-NVs was observed by transmission electron microscopy, and their drug release behavior in phosphate buffer solutions at pH 5.0, 5.5, 6.5, and 7.4 was investigated by in vitro dialysis. A rat model of liver cancer was established, and tail intravenous administration was used to determine the drug concentration in various tissues at different time points for artesunate injection and Gal-Art-NVs, the relative uptake rate (RUE) and peak concentration ratio (Ce) were calculated to evaluate the in vivo targeting of the drug delivery system. Meanwhile, the tumor inhibition rate was calculated to evaluate the in vivo anti-tumor effect of Gal-Art-NVs. Results The optimal formulation of Gal-Art-NVs was as follows: Artesunate concentration of 0.98 mg·mL^-1, the ratio of sorbitan monooleate 80 to cholesterol succinate was 1.93∶ 1.00, the ratio of the carrier to artesunate was 20.77∶ 1.00, and the amount of galactose stearate was 8% of the total carrier mass. After optimization, the average encapsulation efficiency of Gal-Art-NVs was (85.68 ± 1.07)%, the drug loading was (3.91 ± 0.14)%, the particle size was (183.76 ± 7.60) nm, and the ζ potential was (-26.79 ± 1.04) mV, presenting an elliptical vesicular shape. The nanovesicles significantly increased the drug release rate and cumulative release rate of artesunate in phosphate buffer solutions at pH 5.0 and 5.5, demonstrating obvious pH sensitivity. Compared with artesunate injection, the RUE and Ce of Gal-Art-NVs in tumor tissues increased by 3.02 times and 1.95 times, respectively. Compared with the model group, Gal-ArtNVs significantly inhibited tumor growth in nude mice bearing tumors, with an inhibition rate of 64.21% in the Gal-Art-NVs group (30 mg·kg^-1). Conclusion Gal-Art-NVs have pH sensitivity and can increase the accumulation of artesunate in tumor sites, thereby effectively enhancing its anti-tumor efficacy.

R283.6

2024 年河南省科技發(fā)展計(jì)劃資助項(xiàng)目（242102310295）； 2024 年河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃項(xiàng)目（LHGJ20240330）； 2025 年度校級(jí)重點(diǎn)科研項(xiàng)目（2025-XJKY-50）