Halder Shimul, Nasrin Faria, Chandra Shill Manik, Shuma Madhabi Lata, Sultan Md Zakir, Reza Md Selim
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
School of Pharmacy, Brac University, KHA 224, Progati Sarani, Merul Badda, Dhaka 1212, Bangladesh.
Scientifica (Cairo). 2025 Jun 16;2025:9034181. doi: 10.1155/sci5/9034181. eCollection 2025.
Coenzyme Q10 (CoQ) is a powerful antioxidant with neuroprotective characteristics; nevertheless, its clinical use is constrained by inadequate solubility, diminished bioavailability, and limited blood-brain barrier (BBB) penetration. Solid lipid nanoparticles (SLNs) offer a promising approach to improve the biopharmaceutical characteristics and targeted delivery of CoQ to the brain. This study focuses on the strategic formulation and optimization of SLN-CoQ to improve solubility, oral absorption, and BBB permeability. The SLNs with drug loading of 2.5% (w/w) were prepared using a solvent injection technique and physicochemically characterized employing encapsulation efficiency, drug loading, particle size, zeta potential, surface morphology, crystallinity, in vitro drug release behavior, and mucus penetrating behavior. Pharmacokinetic studies were conducted in rats (100 mg-CoQ/kg, p.o.) after oral administration to elucidate the possible enhancement in the oral absorption of CoQ. The SLN-CoQ (F2) exhibited favorable physicochemical characteristics, including optimal particle size (91.6 ± 8.2 nm), zeta potential (-41.7 ± 1.03 mV), high encapsulation efficiency (85.2 ± 5.0), distinct surface morphology, reduced crystallinity, enhanced drug release, and better mucus penetration than crystalline CoQ. In the dissolution test, SLN-CoQ demonstrated a significant enhancement in the dissolution profile of CoQ as exhibited by an 83.6-fold higher dissolved amount of CoQ in 120 min in water in the F2 formulation ratio. Moreover, in the artificial mucus test, a 42-fold increase in mucus permeation was observed for the F2 formulation compared to the crystalline drug. Orally administered CoQ exhibited a higher systemic exposure of CoQ (3.6-fold higher) in SLLN-CoQ compared to crystalline CoQ, with prolonged circulation time and improved tissue distribution (3-fold higher) in rats. The findings suggest that SLN-CoQ offers a feasible nanotechnological method for enhanced drug transport to the brain, potentially aiding therapeutic approaches for neurodegenerative diseases, including Parkinson's and Alzheimer's.
辅酶Q10（CoQ）是一种具有神经保护特性的强大抗氧化剂；然而，其临床应用受到溶解度不足、生物利用度降低和血脑屏障（BBB）穿透有限的限制。固体脂质纳米粒（SLNs）为改善CoQ的生物药剂学特性和向脑内的靶向递送提供了一种有前景的方法。本研究聚焦于SLN-CoQ的策略性制剂开发和优化，以提高其溶解度、口服吸收和血脑屏障通透性。采用溶剂注入技术制备了载药量为2.5%（w/w）的SLNs，并通过包封率、载药量、粒径、zeta电位、表面形态、结晶度、体外药物释放行为和黏液穿透行为对其进行了物理化学表征。口服给药后在大鼠中进行药代动力学研究（100mg-CoQ/kg，口服），以阐明CoQ口服吸收可能的增强情况。SLN-CoQ（F2）表现出良好的物理化学特性，包括最佳粒径（91.6±8.2nm）、zeta电位（-41.7±1.03mV）、高包封率（85.2±5.0）、独特的表面形态、降低的结晶度、增强的药物释放以及比结晶CoQ更好的黏液穿透性。在溶出试验中，SLN-CoQ显示出CoQ溶出曲线的显著增强，如在F2制剂比例下，120分钟内在水中CoQ的溶解量高出83.6倍。此外，在人工黏液试验中，与结晶药物相比，F2制剂的黏液渗透增加了42倍。口服给药的CoQ在SLLN-CoQ中显示出比结晶CoQ更高的全身暴露量（高3.6倍），在大鼠中循环时间延长且组织分布改善（高3倍）。这些发现表明，SLN-CoQ为增强药物向脑内的转运提供了一种可行的纳米技术方法，可能有助于包括帕金森病和阿尔茨海默病在内的神经退行性疾病的治疗方法。
