Pradhan Priyabrata, Rai Vineet Kumar, Halder Jitu, Kar Durgamadhab, Prusty Shakti Ketan, Rout Saroj Kumar, Manoharadas Salim, Palanisamy Subramanian, Dash Priyanka, Das Chandan, Kar Biswakanth, Ghosh Goutam, Rath Goutam
School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Kalinga Nagar, Bhubaneswar, 751030, Odisha, India.
LNK International Inc, Hauppauge, New York, 11788, USA.
AAPS PharmSciTech. 2025 May 6;26(5):124. doi: 10.1208/s12249-025-03119-2.
The present study focuses on developing and optimising chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex (QNPs) using the nanoprecipitation method to enhance quercetin's solubility, stability, and bioavailability. A comprehensive optimization study revealed that Batch B6, which utilized ethanol as the solvent, poloxamer 188 as the stabilizer, and chitosan at a concentration of 0.2% (w/v), exhibits optimal characteristics required for providing a stable colloidal system. The prepared nanoparticles were characterized for their physicochemical properties using FTIR, DSC, X-ray Diffraction, and SEM, which confirmed the successful inclusion of quercetin within the β-cyclodextrin complex and the reduction in crystallinity. In-vitro drug release studies demonstrated a controlled release profile for QNPs compared to free quercetin and the inclusion complex. Pharmacokinetic evaluation in mice via oral administration revealed a significant enhancement in systemic circulation and brain uptake, with QNPs showing a peak plasma concentration of 6.5 µg/mL at 2 h and a brain concentration of 3.5 µg/g at 4 h, indicating improved bioavailability and prolonged retention. In the Pentylenetetrazole and Kainic acid-induced epilepsy mice model, QNP significantly reduced seizure duration, frequency of seizures, and severity scores favoured the QNP formulation over free quercetin. QNPs also exhibited a significant neuroprotective effect by enhancing antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione reductase in brain tissue. Furthermore, Na⁺/K⁺-ATPase activity was significantly preserved in QNP-treated groups, indicating membrane stability and reduced neuronal excitability. These findings suggest that QNPs offer a promising strategy for enhancing quercetin's therapeutic efficacy in neurological disorders such as epilepsy.
本研究聚焦于采用纳米沉淀法开发并优化含有槲皮素-β-环糊精包合物（QNPs）的壳聚糖纳米颗粒，以提高槲皮素的溶解度、稳定性和生物利用度。一项全面的优化研究表明，批次B6利用乙醇作为溶剂、泊洛沙姆188作为稳定剂以及浓度为0.2%（w/v）的壳聚糖，展现出提供稳定胶体系统所需的最佳特性。使用傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、X射线衍射和扫描电子显微镜（SEM）对制备的纳米颗粒进行了物理化学性质表征，证实槲皮素成功包合在β-环糊精复合物中且结晶度降低。体外药物释放研究表明，与游离槲皮素和包合物相比，QNPs具有控释特性。通过口服给药对小鼠进行的药代动力学评估显示，全身循环和脑摄取显著增强，QNPs在2小时时血浆峰值浓度为6.5μg/mL，4小时时脑浓度为3.5μg/g，表明生物利用度提高且保留时间延长。在戊四氮和 kainic 酸诱导的癫痫小鼠模型中，QNP 显著缩短了癫痫发作持续时间、发作频率，且严重程度评分表明 QNP 制剂优于游离槲皮素。QNPs 还通过提高脑组织中超氧化物歧化酶、过氧化氢酶和谷胱甘肽还原酶等抗氧化酶水平，表现出显著的神经保护作用。此外，在 QNP 治疗组中，Na⁺/K⁺-ATP 酶活性得到显著保留，表明膜稳定性和神经元兴奋性降低。这些发现表明，QNPs 为提高槲皮素在癫痫等神经系统疾病中的治疗效果提供了一种有前景的策略。
