背景:小檗碱(BBR),东方传统医学,表达了新的治疗活性,尤其是像糖尿病这样的慢性疾病,高脂血症,高血压,和老年痴呆症。然而,BBR的低口服生物利用度限制了这些治疗的应用。因此,制备负载BBR的固体脂质纳米颗粒(BBR-SLN)以通过该途径改善BBR吸收到全身循环中。
方法:通过超声处理制备负载BBR的固体脂质纳米粒(BBR-SLN),然后通过喷雾干燥技术转化为固体形式。通过动态光散射(DLS)和扫描电子显微镜(SEM)评估BBR-SLN的尺寸形态。通过光谱法检查BBR的结晶度和BBR与其他赋形剂的相互作用。还考虑了BBR-SLN的捕获效率以及在胃肠道条件下的BBR释放。最后,用人胚肾细胞(HEK293)测定负载BBR的SLN细胞毒性。
结果:硬脂酸(SA),单硬脂酸甘油酯(GMS),选择泊洛沙姆407(P407)用于BBRSLN制造。BBR-SLN具有小于200nm的均匀粒径,近90%的高封装效率和12%以上的装载能力。BBR-SLN粉末可再分散,理化性质无明显变化,稳定30天。喷雾干燥的BBR-SLN在初始阶段显示出比BBR-SLN悬浮液和BBR更好的持续体外释放曲线,然后BBR在24小时内完全溶解。值得注意的是,与100µg/mLBBR未加载SLN的对照样品相比,HEK293上的细胞活力甚至增加了150%。
结论:因此,SLN可能揭示了一种有前途的药物递送系统,以扩大口服给药的BBR治疗。
Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities, especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer\'s disease. However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations via this route.
BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN\'s cytotoxicity for loading BBR was determined with human embryonic kidney cells (HEK293).
Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150% compared to the control sample at 100 μg/mL BBR-unloaded SLNs.
Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.