3-Methacryloxypropyltrimethoxysilane-Modified Hydroxyl Acrylate Pressure-Sensitive Adhesive with High Antiplasticity for Efficient Transdermal Drug Delivery

In transdermal patches, pressure-sensitive adhesives (PSAs) are considered the most critical excipients due to their ability to provide adhesion and act as a drug reservoir. However, the loaded drugs plasticize the patches, resulting in a cold flow phenomenon, which poses a product safety risk and reduces treatment efficacy. Herein, 3-methacryloxypropyltrimethoxysilane (KH-570)-modified hydroxyl acrylate PSA (AAOK) was proposed. Diclofenac, ketoprofen, tulobuterol, and oxybutynin were selected as model drugs. The results showed that when not loaded with drugs, the performance of AAOK was not significantly different from that of hydroxyl acrylate PSA (AAOH). Interestingly, when loaded with drugs, AAOK automatically forms a cross-linked system through drug catalysis, which exerts a strong antiplasticity without reducing the ability of AAOK to load and deliver the drug. Specifically, the shear strength of drug-loaded AAOK increased by more than 10-fold compared to AAOH. The cold flow area of drug-loaded AAOK was reduced by more than 15-fold compared to commercial DURO-TAK 87-2287. In addition, the “dark ring” phenomenon was not observed with AAOK compared to that with DURO-TAK 87-2287 on the human forearm after drug loading. After loading four model drugs into AAOK, a high drug loading and efficient drug delivery were endowed for AAOK in vitro and in vivo. The molecular mechanism for the improved antiplasticity of the drug-loaded AAOK was that the drug molecules had a catalyzing effect on the self-condensation reactions of KH-570. This study opens up ideas for the investigation of transdermal patches with high antiplasticity and efficient transdermal application.