Wang Jie, Gu Xuemei, Lv Zhiyang, Chen Jing, Gao Zihan, Hu Xinyun, Xiao Wei
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
School of Pharmacy, Hanlin College of Nanjing University of Chinese Medicine, Taizhou, China.
Pharm Dev Technol. 2025 Jul;30(6):743-758. doi: 10.1080/10837450.2025.2518567. Epub 2025 Jun 13.
This study developed a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-functionalized supersaturated self-nanoemulsifying drug delivery system (HPMCAS-SNEDDS@BA) to address the poor solubility and bioavailability of baicalin (BA), a flavonoid with anti-colitis efficacy. The formulation was systematically optimized through solubility screening, emulsification efficiency evaluation, and pseudo-ternary phase diagram analysis. Central composite design-response surface methodology (CCD-RSM) was employed to identify the optimal SNEDDS@BA composition, followed by HPMCAS ratio optimization based on supersaturation maintenance in biorelevant media. Comprehensive characterization included emulsification performance, droplet morphology, solid-state properties, release, and stability. The optimized formulation (mass ratio: HPMCAS-castor oil-RH40-PEG400-BA = 151.5:20:40:40:1) generated homogeneous, transparent nanoemulsions with spherical droplets, achieving an emulsification time of 48.30 ± 0.74 s, a mean particle size of 47.77 ± 2.32 nm, and a polydispersity index (PDI) of 0.259 ± 0.007. HPMCAS-SNEDDS@BA effectively prevented premature gastric emulsification while enhancing intestinal dissolution rates and sustaining BA supersaturation. Pharmacokinetic studies demonstrated a 5.84-fold improvement in BA bioavailability compared to unmodified formulations. In a dextran sulfate sodium (DSS)-induced colitis model, HPMCAS-SNEDDS@BA outperformed BA suspension and SNEDDS@BA, normalizing colon length, reducing inflammatory cytokines, and restoring mucosal architecture. These findings validate the dual functionality of HPMCAS as a pH-responsive polymer and crystallization inhibitor, enabling targeted intestinal delivery and optimized therapeutic outcomes for ulcerative colitis.
本研究开发了一种羟丙基甲基纤维素琥珀酸酯（HPMCAS）功能化的过饱和自纳米乳化药物递送系统（HPMCAS-SNEDDS@BA），以解决具有抗结肠炎功效的黄酮类化合物黄芩苷（BA）溶解度差和生物利用度低的问题。通过溶解度筛选、乳化效率评估和伪三元相图分析对该制剂进行了系统优化。采用中心复合设计-响应面法（CCD-RSM）确定最佳的SNEDDS@BA组成，随后基于生物相关介质中的过饱和维持对HPMCAS比例进行优化。综合表征包括乳化性能、液滴形态、固态性质、释放和稳定性。优化后的制剂（质量比：HPMCAS-蓖麻油-RH40-PEG400-BA = 151.5:20:40:40:1）产生了具有球形液滴的均匀、透明纳米乳液，乳化时间为48.30±0.74秒，平均粒径为47.77±2.32纳米，多分散指数（PDI）为0.259±0.007。HPMCAS-SNEDDS@BA有效防止了胃内过早乳化，同时提高了肠道溶解速率并维持了BA的过饱和状态。药代动力学研究表明，与未修饰的制剂相比，BA的生物利用度提高了5.84倍。在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中，HPMCAS-SNEDDS@BA的表现优于BA混悬液和SNEDDS@BA，使结肠长度恢复正常，减少炎症细胞因子，并恢复黏膜结构。这些发现验证了HPMCAS作为pH响应性聚合物和结晶抑制剂的双重功能，能够实现溃疡性结肠炎的靶向肠道递送并优化治疗效果。
