Casolaro Mario, Casolaro Ilaria
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena 53100, Italy.
Psychiatry Resident, University of Siena, Siena 53100, Italy.
Gels. 2016 Sep 27;2(4):24. doi: 10.3390/gels2040024.
Some vinyl hydrogels containing α-amino acid residues (l-phenylalanine, l-valine) were used as polyelectrolyte platforms for the evaluation of the controlled release of two antidepressants (paroxetine and duloxetine). The closer acidity constant (pKa) values of the two drugs show a closer release profile in physiological phosphate buffered saline (PBS) buffer (pH 7.40) and for long periods of time. The great electrostatic interaction forces between the COO group of the hydrogel and the protonated secondary amino nitrogen of the drug are the main factor improving the release kinetics; this release was found to be slower compared to that of two structurally related drugs bearing the tertiary amino nitrogen atom (citalopram and trazodone). Moreover, at the lower value of pH 4.60, paroxetine showed a flatter release profile from the hydrogel containing the l-phenylalanine residues that, after six days, is half of that shown by duloxetine. Further effects due to steric and hydrophobic interactions may contribute to the different release profile. A further stimulation with alternating magnetic fields (AMF) of low frequency (20 kHz/50 W) enhanced the release of the drug at pH 7.40 from the hydrogel containing magnetic nanoparticles. Both AMF and PBS solution at pH 7.40 were used to trigger the 'on-demand' pulsatile paroxetine release from the nanocomposite hydrogel.
一些含有α-氨基酸残基(L-苯丙氨酸、L-缬氨酸)的乙烯基水凝胶被用作聚电解质平台,用于评估两种抗抑郁药(帕罗西汀和度洛西汀)的控释情况。两种药物相近的酸度常数(pKa)值表明,在生理磷酸盐缓冲盐水(PBS)缓冲液(pH 7.40)中且在较长时间内,它们的释放曲线较为相近。水凝胶的COO基团与药物质子化的仲氨基氮之间强大的静电相互作用力是改善释放动力学的主要因素;与带有叔氨基氮原子的两种结构相关药物(西酞普兰和曲唑酮)相比,发现这种释放较慢。此外,在pH 4.60的较低值下,帕罗西汀从含有L-苯丙氨酸残基的水凝胶中显示出较平缓的释放曲线,六天后,该释放量是度洛西汀的一半。空间和疏水相互作用产生的进一步影响可能导致不同的释放曲线。低频(20 kHz/50 W)交变磁场(AMF)的进一步刺激增强了药物在pH 7.40时从含有磁性纳米颗粒的水凝胶中的释放。AMF和pH 7.40的PBS溶液都被用于触发纳米复合水凝胶中“按需”脉冲式释放帕罗西汀。