Dedroog Sien, Ouyang Jiabi, Vaes Elise, Willemse Filip, Andersen Sune Klint, den Mooter Guy Van
Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium.
Johnson & Johnson Innovative Medicine, Turnhoutseweg 30, 2340 Beerse, Belgium.
Eur J Pharm Biopharm. 2025 Oct;215:114818. doi: 10.1016/j.ejpb.2025.114818. Epub 2025 Jul 29.
A dual trigger coating was designed by Ibekwe et al. to achieve site-specific delivery of therapeutics to the colon. It consists essentially of Eudragit® S 100 (EU S 100), a polymer that dissolves above pH 7, and resistant starch, which can only be degraded by enzymes produced by colonic bacteria. Both components should maintain the integrity of the coating until reaching the colonic region and ensure drug release when reaching it. The contribution of these components was investigated in the present study by permeability testing and enzymatic degradation testing of free polymer films produced using an in-house built spraying device. Diffusion testing of EU S 100 films showed no impact of the pH (2, 4, 6) and plasticizer levels (25, 30, 35 % w/w triethyl citrate (TEC)) on the permeability of the films. The permeability of the resistant starch-Eudragit® S 100 (RS-EU S 100) films was also not affected by the pH, however, the permeability coefficient of films containing 35 % w/w TEC was significantly higher for all pH levels. Incubating the RS-EU S 100 films with enzyme resulted in a higher permeability for films with 25 % w/w TEC, yet the presence of enzyme had no effect on the permeability of 35 % w/w TEC films. For the 25 % w/w TEC films, even if EU S 100 does not dissolve (pH < 7), the resistant starch in the RS-EU S 100 film can be enzymatically degraded. Using n-butanol in the preparation process of the RS-EU S 100 films resulted in a lower permeability coefficient compared to the RS-EU S 100 films without n-butanol for all pH and plasticizer levels. n-Butanol forms a V-type complex with amylose, which makes the films less susceptible to enzymatic degradation. The permeability and susceptibility to enzymatic degradation of the RS-EU S 100 coating can be adapted by altering the amount of plasticizer and the use of n-butanol during the production process.
伊贝奎等人设计了一种双重触发涂层，以实现治疗药物在结肠的特定部位递送。它主要由Eudragit® S 100（EU S 100）和抗性淀粉组成，EU S 100是一种在pH值高于7时溶解的聚合物，而抗性淀粉只能被结肠细菌产生的酶降解。两种成分在到达结肠区域之前都应保持涂层的完整性，并在到达时确保药物释放。在本研究中，通过使用自制喷雾装置生产的游离聚合物薄膜的渗透性测试和酶降解测试，研究了这些成分的作用。EU S 100薄膜的扩散测试表明，pH值（2、4、6）和增塑剂水平（25%、30%、35% w/w柠檬酸三乙酯（TEC））对薄膜的渗透性没有影响。抗性淀粉-Eudragit® S 100（RS-EU S 100）薄膜的渗透性也不受pH值影响，然而，对于所有pH水平，含有35% w/w TEC的薄膜的渗透系数显著更高。用酶孵育RS-EU S 100薄膜会使含有25% w/w TEC的薄膜具有更高的渗透性，但酶的存在对含有35% w/w TEC的薄膜的渗透性没有影响。对于含有25% w/w TEC的薄膜，即使EU S 100不溶解（pH < 7），RS-EU S 100薄膜中的抗性淀粉也可以被酶降解。在RS-EU S 100薄膜的制备过程中使用正丁醇，与不含正丁醇的RS-EU S 100薄膜相比，在所有pH值和增塑剂水平下，其渗透系数都更低。正丁醇与直链淀粉形成V型络合物，这使得薄膜更不易被酶降解。通过改变增塑剂的用量以及在生产过程中使用正丁醇，可以调整RS-EU S 100涂层的渗透性和酶降解敏感性。
