目的 采用星点设计-效应面法（central composite design-response surface methodology，CCD-RSM）优化pH值依赖型岩黄连碱口服结肠靶向纳米粒（dehydrocavidine-chitosan/pectin-nanoparticles，DC-CS/PT-NPs）制备工艺，并对其进行质量表征及体外释放行为评价。方法 采用离子凝胶法制备DC-CS/PT-NPs，以粒径、PDI、ζ电位、包封率、载药量作为评价指标，采用单因素考察和CCD-RSM优化DC-CS/PT-NPs制备工艺。通过透射电子显微镜（transmission electron microscope，TEM）、扫描电子显微镜（scanning electron microscope，SEM）、傅里叶红外光谱（Fourier transform infrared spectroscopy，FT-IR）、差示扫描量热法（differential scanning calorimetry，DSC）和X射线衍射法（X-ray diffraction，XRD）对DC-CS/PT-NPs进行表征，并进行体外释放性能评价。结果 最佳处方为壳聚糖质量浓度为1.5 mg/mL，果胶质量浓度为1.5 mg/mL，TPP质量浓度为2.0 mg/mL，壳聚糖pH值为5.0。DC-CS/PT-NPs包封率为（61.64±1.77）%，载药量为（8.05±0.18）%，粒径为（418.65±4.92）nm，ζ电位为（−14.14±0.22）mV。DC-CS/PT-NPs呈均匀的球形或类球形；制备成纳米粒后，药物的晶型发生了改变；体外释药结果表明，DC-CS/PT-NPs在人工胃液中2 h仅释放24.35%，在人工小肠液中4 h累积释放率＜40%，在人工结肠液中10 h累积释放率＞85%。结论 CCD-RSM所建立的模型可用于DC-CS/PT-NPs处方优化，DC-CS/PT- NPs具有良好的体外结肠释药特征。

Objective To optimize the formulation of pH-dependent dehydrocavidine-chitosan/pectin-nanoparticles (DC-CS/PT-NPs) by central composite design-response surface methodology (CCD-RSM), and to conduct its quality characterization and evaluate its release behavior in vitro. Methods DC-CS/PT-NPs was prepared by ionotropic gelation method. Particle size, PDI, ζ potential, encapsulation rate and drug loading were used as evaluation indexes, and the preparation process of DC-CS/PT-NPs was optimized by single factor investigation and CCD-RSM. DC-CS/PT-NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD), and their release properties were evaluated in vitro. Results The optimal prescription is chitosan concentration of 1.5 mg/mL, pectin concentration of 1.5 mg/mL, TPP concentration of 2.0 mg/mL, and chitosan pH of 5.0. The encapsulation rate of DC-CS/PT-NPs was (61.64 ± 1.77)%, the drug loading was (8.05 ± 0.18)%, the particle size was (418.65 ± 4.92) nm, and the ζ potential was (−14.14 ± 0.22) mV. DC-CS/PT-NPs are uniformly spherical or quasi-spherical; The crystalline form of the drug was changed after the preparation of nanoparticles. The results of drug release in vitro showed that only 24.35% of DC-CS/PT-NPs were released in artificial gastric fluid for 2 h, and the cumulative release rate was less than 40% in artificial intestinal fluid for 4 h and more than 85% in artificial colonic fluid for 10 h. Conclusion The model established by CCD-RSM can be used to optimize the formulation of DC-CS/PT-NPs, which has good characteristic of colonic drug release in vitro.

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国家自然科学基金资助项目（82360818）；国家自然科学基金资助项目（81960756）；广西自然科学基金资助项目（2022GXNSFDA035063）；广西自然科学基金资助项目（2023GXNSFAA026366）