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鼻腔内给予舒必利纳米结构脂质载体至中枢神经系统;体外特征和体内研究。

Intranasal delivery of sulpiride nanostructured lipid carrier to central nervous system; in vitro characterization and in vivo study.

机构信息

Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt.

出版信息

Pharm Dev Technol. 2024 Oct;29(8):841-854. doi: 10.1080/10837450.2024.2404034. Epub 2024 Sep 24.

Abstract

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL release, nanodispersion stability, performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly ( < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.

摘要

舒必利(SUL)是一种多巴胺受体拮抗剂,其口服吸收低且不稳定,并且在胃肠道中具有 P 糖蛋白外排作用,这限制了其用于治疗中枢神经系统疾病的口服途径。本研究基于纳米结构脂质载体(NLC)制备了一种鼻腔给药制剂,以克服这些障碍,并将 SUL 直接递送到大脑。采用 Compritol888 ATO 和不同类型的液体脂质及乳化剂制备载 SUL 的 NLC(SUL-NLC)。对 SUL-NLC 的粒径、表面电荷和包封效率进行了评价。还研究了其形态和与其他 NLC 赋形剂的相容性。此外,还对 SUL 释放、纳米分散体稳定性、鼻腔给药制剂的性能和 SUL 药代动力学进行了考察。结果表明,SUL-NLC 的粒径为 366.2 ± 62.1 至 640.4 ± 50.2nm,包封效率为 75.5 ± 1.5%。SUL 呈现出 24h 内的持续释放模式,并在三个月内保持其物理稳定性。与口服市售 SUL 产品相比,鼻腔给予 SUL-NLC 后,SUL 的脑浓度显著升高(<0.01),相对生物利用度提高了 4.47 倍。NLC 作为一种经鼻递药途径,是提高 SUL 生物利用度和有效治疗神经紊乱的有前途的制剂。

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