Association mechanism of remimazolam-serum albumin nano-drug for potential clinical application. (March 2022)

• Record Type: Journal Article
• Authors: Zhang, Jianzhong; Wang, Tianyi; Shao, Wei; Huang, Shaoyan; Ma, Huashan
• Is Part Of: Process biochemistry. Volume 114(2022)
• Page Start: 156
• Page End: 162
• Publication Date: 2022-03
• Subjects: Remimazolam -- Nano-drug -- Controlled release -- Serum albumin -- Protein conformation; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2022.01.027
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Highlights: Remimazolam-BSA nanoparticles were prepared by thermal denaturation. Interaction mechanism of BSA and Remimazolam was studied. The nanoparticle exhibits controlled drug release. Conformational alterations of BSA were caused by remimazolam binding. Abstract: Bovine serum albumin (BSA) was selected to act as a stabilizer for the growth of remimazolam-BSA particles using thermal denaturation precipitation. The remimazolam-BSA NPs showed a sphere shape, with a ζ-potential of −11.3 mV and an average diameter of 84.3 nm under electron microscopy. The drug release study of remimazolam in vitro showed a sustained and controlled release pattern. The common ways of spectroscopy like circular dichroism (CD), UV–vis, and steady-state fluorescence were all used to investigate the physicochemical association properties. A moderate binding affinity between BSA and remimazolam with a stoichiometry of 1:1 was revealed by fluorescence results (binding constant: 1.87 × 10 4 M −1 at body temperature). The participation of hydrophobic forces in the formation of the complex has been confirmed by analyzing the thermodynamic results of the binding data (Δ S ○ = 110 J mol -1 K -1 and Δ H ○ = 8.63 × 10 3 J mol -1 ). The prior remimazolam binding site is located in site II of BSA with slight protein conformational changes and probable energy transfer.