Surface molecular imprinted membranes as a “gate” for selective transdermal release of chiral drug amlodipine

Abstract

Amlodipine is a commonly used and effective drug for the treatment of hypertension. This work investigates imprinted membranes with functional molecular recognition properties prepared via the surface molecular imprinted technology. The surface molecular imprinted membrane are synthesized by taking (S)-amlodipine (S-ADP) as the template molecule, methacrylic acid (MAA) as the functional monomer, and N, N′-methylenebisacrylamide (MBA) as the cross-linker in the present of a surface-initiating system of –OH/Ce4+ constituted by the hydroxyl on the surface of basilemma polyvinyl alcohol (PVA) and ammonium cerium sulfate dissolved in solvent.The imprinted layer is grafted onto the PVA membranes followed by the removal of the S-ADP template molecule, obtaining the S-ADP surface molecular imprinted membranes (S-ADP-SMIMs). The membrane is characterized by Fourier transform infrared reflection (FTIR), and scanning electron microscopy (SEM),13C Nuclear Magnetic Resonance spectroscopy (13C NMR) and X-ray photoelectron spectroscopy (XPS). The ability of enantioseparation and selective permeability of S-ADP-SMIMs is studies. As a result, the selectivity coefficient is 4.6 and the optical purity of adsorption liquid gets up to 80% for S-ADP-SMIMs. However, the non-surface molecular imprinted membrane (NSMIM) shows no selectivity. And the results of in vitro release experiments reveal that the cumulative amounts released of S-ADP and R-amlodipine (R-ADP) is 1459.01 μg cm−2 and 106.21 μg cm−2, respectively. In the skin permeation experiments, the optimal drug concentration is 4.0 mg/mL, Carbopol is determined 0.9% and 1% oleic acid is acted as excellent permeation enhancer. The cumulative amount transported reaches 1719.68 μg cm−2 for S-ADP, while a lower value of 228.17 μg cm−2 is measured for R-ADP. These results strongly suggest the formation of imprinted cavities, which offer selectivity for the transport of S-ADP. So, the imprinted membrane is universal for other chiral drugs. It makes it possible to selectively delivery dominant isomers exactly and efficiently.