Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, 977 Gongyuan Road, Yanji 133002, China.
Acta Biomater. 2024 Apr 15;179:130-148. doi: 10.1016/j.actbio.2024.02.045. Epub 2024 Mar 7.
Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.
压敏胶（PSA）在经皮给药系统（TDDS）中普遍存在皮肤附着力和机械性能差、亲水性差的问题。其亲水性差导致贴片在应用部位出汗或浸泡后脱落。为解决这一问题，设计了交联型吡咯烷酮聚丙烯酸酯 PSA 聚（2-乙基己基丙烯酸酯-co-N-乙烯基-2-吡咯烷酮-co-N-（2-羟乙基）丙烯酰胺）（PENH），通过静电力和氢键体系提高 PSA 的附着力和耐水性。采用 1H NMR、FTIR、DSC 等方法对 PENH 的结构进行了表征。采用 FTIR、流变测试和分子模拟等方法研究了 PENH 的成胶机制。结果表明，PENH 贴片在无冷流的情况下可在人体皮肤上附着 10 天以上，且在出汗或接触水后仍能附着。相比之下，商用 PSA Duro-Tak® 87-4098 和 Duro-Tak® 87-2852 在第 3 天和第 6 天完全脱落，而 Duro-Tak® 87-2510 在第 2 天出现明显的暗环。机制研究表明，2-乙基己基丙烯酸酯（2-EHA）、N-乙烯基-2-吡咯烷酮（NVP）和 N-（2-羟乙基）丙烯酰胺（HEAA）形成的氢键增强了内聚性，与皮肤的相互作用提高了皮肤的附着力，与水或药物分子的静电相互作用增强了吸水和载药能力。由于氢键和静电力的协同作用，PENH 在载药或吸水后仍能保持较高的内聚性。PENH 为开发具有持久附着力的亲水性贴片提供了选择。意义声明：基于氢键和静电力的协同作用，设计并合成了一种用于经皮给药的氢键交联吡咯烷酮丙烯酸盐压敏胶，具有高附着力和内聚强度，对皮肤无刺激性。贴片可连续贴附在皮肤表面 10 天以上，无“暗环”现象，患者出汗或洗澡后仍保持附着。这为选择需要长期给药的贴片基质提供了一个很好的策略。
