Sustained Release of Co-Amorphous Matrine-Type Alkaloids and Resveratrol with Anti-COVID-19 Potential

Abstract

Matrine (MAR), oxymatrine (OMAR), and sophoridine (SPD) are natural alkaloids with varying biological activities; matrine was recently used for the treatment of coronavirus disease 2019 (COVID-19). However, the short half-lives and rapid elimination of these matrine-type alkaloids would lead to low oral bioavailability and serious side effects. Herein, resveratrol (RES) was selected as a co-former to prepare their co-amorphous systems to improve the therapeutic index. The formation of co-amorphous MAR-RES, OMAR-RES, and SPD-RES was established through powder X-ray diffraction and modulated temperature differential scanning calorimetry. Furthermore, Fourier transform infrared spectroscopy and NMR studies revealed the strong molecular interactions between resveratrol and these alkaloids, especially OMAR-RES. Matrine, oxymatrine, and sophoridine in the co-amorphous systems showed sustained release behaviors in the dissolution experiments, due to the recrystallization of resveratrol on the surface of co-amorphous drugs. The three co-amorphous systems exhibited excellent physicochemical stability under high relative humidity conditions. Our study not only showed that minor structural changes of active pharmaceutical ingredients may have distinct molecular interactions with the co-former, but also discovered a new type of sustained release mechanism for co-amorphous drugs. This promising co-amorphous drug approach may present a unique opportunity for repurposing these very promising drugs against COVID-19.

Investigation of the preparation, characterization, and whitening activity of co-amorphous glabridin and oxymatrine

“…This phenomenon may be attributed to converting a partially hydrated form of OMT into a trihydrate form. This crystallization phenomenon is consistent with the results of Hu et al 51 The moisture sorption weight gain of co-amorphous Gla–OMT is 0.74%, which is greater than 0.2%, and it belongs to the slightly hygroscopic property. Compared to crystalline Gla, the hygroscopicity of the co-amorphous Gla–OMT system is significantly enhanced.…”

Zein nanoparticles stabilized by hydrophilic small molecule stabilizer matrine deliver curcumin effectively

“…In the FTIR spectra of MAR, aliphatic C-H stretching and bending vibrations is represented by bands at 2937 and 1440 cm −l , respectively. The C=O stretching vibration typical of lactam functional groups is observed at 1647 cm −l , while bands at 1340 cm −l and 1254 cm −l indicate the presence of characteristic C-N stretching vibrations, in agreement with previous reports [33]. However, after the formation of ZMNPs, the characteristic peaks of pure MAR were not observed in the ZMNPs spectra, and these hidden characteristic peaks suggest that MAR acts between zein or is encapsulated in the nanoparticles.…”

“…MAR has been encapsulated as active substance in nano-carrier [28][29][30][31][32]. Hu et al, recently prepared the hydrophobic polyphenol resveratrol and hydrophilic alkaloids, including matrine, oxymatrine, and sophoridine, to form three novel co-amorphous drug systems with significant anti-covid-19 effects [33]. Intermolecular interactions were observed between the O-H groups of resveratrol and the C=O groups of the three similarly structured alkaloids.…”

Combining multiple acquisition modes and computational data annotation for structural characterization in traditional Chinese medicine: Miao Nationality medicine Qijiao Shengbai Capsule as a case study

“…Matrine-type alkaloids were the major constituents of SF, which show potential pharmacological activities on anti-tumor 27 and anti-COVID-19. 28 They exhibited high mass spectrometry responses in positive ion mode due to the addictive of formic acid in the mobile phase. Generally, the matrine-type alkaloids are easy to experience the ring cleavage on the absence of unsaturated bonds of four rings.…”