Chiral selective construction of “gate-controlled” surface molecularly imprinted membrane and regulation of transdermal drug delivery system

To address the efficacy differences and side effects of amlodipine (ADP) enantiomers, this study innovatively developed a surface molecularly imprinted membrane (S-ADP@SNP-SMIM) for the specific recognition and selective separation of S-ADP. The membrane was constructed via synchronous grafting polymerization and cross-linked imprinting on the SiO 2 -NH 2 /PSF composite membrane substrate, utilizing methacrylic acid (MAA) and N,N’-methylene bisacrylamide (MBA) as the functional monomer and cross-linking agent, respectively. The imprinted membrane achieved efficient recognition of S-ADP through hydrogen bonding and ionic interactions, with a selectivity coefficient reached 4.18. The cumulative release amount of S-ADP through S-ADP@SNP-SMIM reached 1608.76 μg/cm 2 within 24 h, significantly higher than that of R-ADP (139.97 μg/cm 2 ). In addition, leveraging the selective release properties of the imprinted membrane, a transdermal preparation was developed using 0.7 % carbomer as the matrix, 4 mg/mL racemic ADP solution as the drug-loading system, and a combined osmotic enhancer of 1 % oleic acid and azone. The cumulative transdermal transported volume of S-ADP in this transdermal preparation reached 1884.45 μg/cm 2 within 24 h, while that of R-ADP was only 176.47 μg/cm 2 , highlighting the regulatory role of imprinted recognition sites in selective transport. This study presented a surface molecularly imprinted membrane strategy that achieved precise separation of the superior isomer S-ADP, resolving enantiomeric efficacy disparities in amlodipine. This approach provided a dual-functional platform for establishing a universal framework for enantiomer-selective delivery systems of chiral drugs and mitigating clinical side effects.