Li Yongqiang, Wong Ho Lun, Shuhendler Adam J, Rauth Andrew M, Wu Xiao Yu
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
J Control Release. 2008 May 22;128(1):60-70. doi: 10.1016/j.jconrel.2008.02.014. Epub 2008 Mar 5.
This paper presents the first study of molecular interactions of ingredients and internal nanostructure in relation to drug loading and release mechanisms/kinetics of rationally designed solid polymer-lipid hybrid nanoparticles (PLN). The PLN were prepared by using a rationally selected composition that was found in our previous work to provide optimized interactions of verapamil hydrochloride (VRP) with dextran sulfate sodium (DS) and then the VRP-DS complex with dodecanoic acid (DA). The solid-state properties of the components, their molecular interactions and the morphology, particle size and internal structure of PLN were determined by use of differential scanning calorimetry, powder X-ray diffraction, (13)C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The distribution of VRP in PLN was examined by TEM imaging using a cationic gold tracer. Drug release studies were conducted in various media. Drug loading as high as 36% and loading efficiencies up to 99% were achieved in the rationally formulated PLN. Hydrogen bonding between drug, polymer and lipid and a uniform distribution of amorphous VRP within the solid lipid matrix were evident. Sustained drug release from the PLN was mainly controlled by ion exchange and diffusion processes. The results demonstrated that strong molecular interactions among the drug, the polymer and the lipid in the optimized formulation were responsible for the improved drug loading and release performance of the PLN.
本文首次研究了合理设计的固体聚合物-脂质杂化纳米粒（PLN）中成分的分子相互作用和内部纳米结构与药物负载及释放机制/动力学之间的关系。PLN是通过使用在我们之前的工作中发现的合理选择的组合物制备的，该组合物能使盐酸维拉帕米（VRP）与硫酸葡聚糖钠（DS）实现优化相互作用，进而使VRP-DS复合物与十二烷酸（DA）相互作用。通过差示扫描量热法、粉末X射线衍射、（13）C核磁共振、傅里叶变换红外光谱、透射电子显微镜（TEM）和动态光散射来测定各组分的固态性质、它们的分子相互作用以及PLN的形态、粒径和内部结构。使用阳离子金示踪剂通过TEM成像检查VRP在PLN中的分布。在各种介质中进行药物释放研究。在合理配制的PLN中实现了高达36%的药物负载量和高达99%的负载效率。药物、聚合物和脂质之间的氢键以及无定形VRP在固体脂质基质中的均匀分布很明显。PLN的持续药物释放主要受离子交换和扩散过程控制。结果表明，优化配方中药物、聚合物和脂质之间强烈的分子相互作用是PLN药物负载和释放性能提高的原因。
