Singh Anurag Kumar, Singh Snigdha, Minocha Tarun, Yadav Sanjeev Kumar, Narayan Reema, Nayak Usha Yogendra, Singh Santosh Kumar, Awasthi Rajendra
Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University Varanasi 221005 Uttar Pradesh India
Department of Zoology, Institute of Science, Banaras Hindu University Varanasi 221005 India.
Nanoscale Adv. 2024 Apr 4;6(9):2469-2486. doi: 10.1039/d3na01142a. eCollection 2024 Apr 30.
Neuronal loss in Alzheimer's disease has been reported to display features of apoptosis, pyroptosis (programmed necrosis), or necroptosis. This study thoroughly examines the production and characterization of MCM-41 based berberine (BBR)-loaded porous silica nanoparticles (MSNs) by a modified Stöber method, focusing on their possible role in inhibiting the apoptotic process. Particle size, polydispersity index, morphology, drug loading, zeta potential, entrapment efficiency, and drug release were examined. The formulation was analyzed using various spectroscopic techniques. The surface area was computed by the Brunauer-Emmett-Teller plot. Computational models were developed for molecular dynamics simulation studies. A small PDI value indicated an even distribution of particles at nanoscale sizes (80-100 nm). Results from XRD and SEAD experiments confirmed the amorphous nature of BBR in nanoparticles. Nanoparticles had high entrapment (75.21 ± 1.55%) and drug loading (28.16 ± 2.5%) efficiencies. A negative zeta potential value (-36.861.1 mV) indicates the presence of silanol groups on the surface of silica. AFM findings reveal bumps due to the surface drug that contributed to the improved roughness of the MSNs-BBR surface. Thermal gravimetric analysis confirmed the presence of BBR in MSNs. Drug release was controlled by simple diffusion or quasi-diffusion. Molecular dynamics simulations confirmed the existence of diffused drug molecules. Cellular studies using SH-SY-5Y cells revealed dose-dependent growth inhibition. Fragmented cell nuclei and nuclear apoptotic bodies in DAPI-stained cells exposed to nanoparticles showed an increase in apoptotic cells. Flow cytometry analysis demonstrated a lower red-to-green ratio in SH-SY-5Y cells treated with nanoparticles. This suggests improved mitochondrial health, cellular viability restoration, and prevention of the apoptotic process. This study provides essential data on the synthesis and potential of MSNs loaded with BBR, which may serve as a viable therapeutic intervention for conditions associated with apoptosis.
据报道，阿尔茨海默病中的神经元损失表现出凋亡、焦亡（程序性坏死）或坏死性凋亡的特征。本研究通过改良的Stöber方法全面研究了基于MCM - 41的载有黄连素（BBR）的多孔二氧化硅纳米颗粒（MSNs）的制备及其特性，重点关注它们在抑制凋亡过程中的可能作用。检测了粒径、多分散指数、形态、载药量、zeta电位、包封率和药物释放情况。使用各种光谱技术对该制剂进行了分析。通过Brunauer - Emmett - Teller图计算表面积。开发了用于分子动力学模拟研究的计算模型。小的PDI值表明颗粒在纳米尺度（80 - 100 nm）上分布均匀。XRD和SEAD实验结果证实了纳米颗粒中BBR的无定形性质。纳米颗粒具有高包封率（75.21 ± 1.55%）和载药量（28.16 ± 2.5%）效率。负的zeta电位值（-36.86 ± 1.1 mV）表明二氧化硅表面存在硅醇基团。原子力显微镜（AFM）结果显示由于表面药物导致的凸起，这有助于改善MSNs - BBR表面的粗糙度。热重分析证实了MSNs中存在BBR。药物释放通过简单扩散或准扩散控制。分子动力学模拟证实了扩散药物分子的存在。使用SH - SY - 5Y细胞进行的细胞研究显示出剂量依赖性生长抑制。暴露于纳米颗粒的DAPI染色细胞中的细胞核碎片化和核凋亡小体表明凋亡细胞增加。流式细胞术分析表明，用纳米颗粒处理的SH - SY - 5Y细胞中红/绿比值降低。这表明线粒体健康状况改善、细胞活力恢复以及凋亡过程得到预防。本研究提供了关于载有BBR的MSNs的合成及其潜力的重要数据，这可能作为与凋亡相关病症的一种可行的治疗干预手段。
