载有头孢曲松的白蛋白基纳米颗粒掺入原位离子敏感鼻用凝胶:研制、表征及鼻内药物沉积研究。

Ceftriaxone-loaded albumin-based nanoparticles incorporated into in situ ionic sensitive nasal gels: Development, characterization, and nasal drug deposition studies.

作者信息

Mardikasari Sandra Aulia, Katona Gábor, Nodilo Laura Nižić, Hafner Anita, Kalogjera Livije, Zadravec Dijana, Orosz László, Burian Katalin, Balogh György Tibor, Csóka Ildikó

机构信息

Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary; Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.

Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary.

出版信息

Eur J Pharm Biopharm. 2025 Jul;212:114743. doi: 10.1016/j.ejpb.2025.114743. Epub 2025 May 9.

Abstract

Ceftriaxone (CFT) is recommended as the drug of choice for the empirical treatment of bacterial meningitis. However, conventional drug delivery has difficulty in crossing the blood-brain barrier (BBB), leading to insufficient therapeutic efficacy. Therefore, nasal drug administration emerged as a viable strategy, providing the opportunity for brain-targeted delivery to reach effective brain concentrations. In this work, we present the development of in situ nasal gels of CFT-loaded albumin nanoparticles for nose-to-brain delivery. The obtained formulations were characterized in terms of particle size, zeta potential, entrapment efficiency, expansion coefficient, droplet size distribution, in vitro drug release, permeability assay, nasal deposition studies, and antibacterial activities. The BBB-PAMPA permeability assay showed that the in situ nasal gels CFT formulation with 0.2% gellan gum (CFT-GG0.2%) has the highest permeation flux of all. Moreover, nasal deposition studies utilizing a 3D-printed human nasal cavity model revealed that CFT-GG0.2% was able to provide higher CFT concentration in the olfactory area. Interestingly, the developed in situ nasal gels formulation could successfully retain the antibacterial activities of CFT against S. agalactiae, H. influenzae, and N. meningitidis. Altogether, the in situ nasal gels formulation has the potential as a suitable delivery platform for CFT administration through the nose-to-brain delivery pathway.

摘要

头孢曲松(CFT)被推荐作为细菌性脑膜炎经验性治疗的首选药物。然而,传统的药物递送难以穿过血脑屏障(BBB),导致治疗效果不佳。因此,鼻腔给药成为一种可行的策略,为脑靶向递送提供了机会,以达到有效的脑内浓度。在这项工作中,我们展示了用于鼻脑递送的载CFT白蛋白纳米粒原位鼻腔凝胶的研发。对所获得的制剂进行了粒径、zeta电位、包封率、膨胀系数、液滴大小分布、体外药物释放、渗透性测定、鼻腔沉积研究和抗菌活性等方面的表征。BBB-PAMPA渗透性测定表明,含0.2%结冷胶的CFT原位鼻腔凝胶制剂(CFT-GG0.2%)在所有制剂中具有最高的渗透通量。此外,利用3D打印的人体鼻腔模型进行的鼻腔沉积研究表明,CFT-GG0.2%能够在嗅觉区域提供更高的CFT浓度。有趣的是,所研发的原位鼻腔凝胶制剂能够成功保留CFT对无乳链球菌、流感嗜血杆菌和脑膜炎奈瑟菌的抗菌活性。总之,原位鼻腔凝胶制剂有潜力作为一种合适的递送平台,通过鼻脑递送途径给药CFT。

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