目的 制备一种包载白藜芦醇（resveratrol）的新型纳米囊泡（spanlastics，SPs），旨在提高药物在角膜前的滞留时间，用于治疗青光眼的眼部药物递送。方法 采用乙醇注入法，制备β-环糊精-壳聚糖修饰的白藜芦醇纳米囊泡（β-CD-CS-Res-SPs）。建立HPLC法测量其包封率和载药量，使用粒径仪、红外光谱仪和差示扫描量热仪对其进行制剂学表征。通过体外释放、刺激性、细胞摄取和体内药动学等对其有效性和安全性进行全面评估。结果 β-CD-CS-Res-SPs形态圆整，平均粒径为（301.40±2.57）nm、PDI为0.265±0.010、ζ电位为（33.50±0.72）mV，包封率和载药量分别为（92.78±2.81）%和（2.37±0.12）%。体外释放结果表明，与白藜芦醇溶液相比，β-CD-CS-Res-SPs中白藜芦醇的释放更为缓慢，说明其具有一定缓释效果；刺激性和细胞生物学研究表明，其安全无刺激，细胞无毒性且能够进入细胞核发挥作用；药动学研究表明，β-CD-CS-Res-SPs能够延长眼部滞留而提高生物利用度，较白藜芦醇溶液相比，生物利用度提高2.71倍。结论 制备的β-CD-CS-Res-SPs包封率高、粒径和ζ电位适宜，是一种安全、无刺激性、具有缓释作用的纳米给药系统，可延长药物在角膜前的滞留时间，从而提高生物利用度。

Objective To prepare a novel type of spanlastics encapsulated with resveratrol, aiming to increase the retention time of the drug in front of the cornea for ocular drug delivery in the treatment of glaucoma. Methods β-Cyclodextrin-chitosan-modified resveratrol spanlastics (β-CD-CS-Res-SPs) were prepared by ethanol injection. The encapsulation efficiency and drug loading were measured by HPLC, and the formulation characterization was carried out using particle size analysis, infrared spectra analysis and differential scanning calorimetry. Its efficacy and safety were comprehensively evaluated through in vitro release, irritation, cellular uptake and in vivo pharmacokinetics. Results The results showed that the morphology of β-CD-CS-Res-SPs was round, the average particle size was (301.40 ± 2.57) nm, the PDI was 0.265 ± 0.010, the ζ potential was (33.50 ± 0.72) mV, and the encapsulation efficiency and drug loading were respectively (92.78 ± 2.81)% and (2.37 ± 0.12)%. The in vitro release results indicated that β-CD-CS-Res-SPs released more slowly than the resveratrol solution and had a certain sustained-release effect. Irritation and cell biology studies have shown that it is safe and non-irritating, non-toxic to cells and capable of entering the cell nucleus to function. Pharmacokinetic studies have shown that β-CD-CS-Res-SPs can prolong ocular retention and improve bioavailability. Compared with the resveratrol solution, the bioavailability is increased by 2.71 times. Conclusion The prepared β-CD-CS-Res-SPs have a high encapsulation efficiency, appropriate particle size and ζ potential. It is a safe, non-irritating and sustained-release nano-drug delivery system, which can prolong the retention time of drugs in front of the cornea and thus improve bioavailability.

R283.6

天津市科技计划项目：芪参益气滴丸的新质生产力培育（24ZXZKSY00030）；企事业单位委托科技项目：六味地黄丸（异型小蜜丸）体外释放及药代动力学研究（HX2024-136）