Intranasal propranolol hydrochloride-loaded PLGA-lipid hybrid nanoparticles for brain targeting: Optimization and biodistribution study by radiobiological evaluation

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2025-03-07 DOI:10.1016/j.ejps.2025.107061
Rofida Albash , Abdurrahman M. Fahmy , Hesham A. Shamsel-Din , Ahmed B. Ibrahim , Hanin A. Bogari , Rania T. Malatani , Manar Adel Abdelbari , Shaimaa Mosallam
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Abstract

The present work aimed to load propranolol hydrochloride (PN), a beta-blocking agent with low oral bioavailability, into PLGA-lipid hybrid nanoparticles (PLHNPs) for augmenting its efficacy. PLHNPs contain phospholipid (PC) in addition to PLGA to augment the potential of PLGA nanoparticles in the intranasal delivery and PN avoidance of the blood–brain barrier for the management of migraine. PLHNPs were prepared by single emulsion/ solvent evaporation method and then optimized by applying 23 full factorial design using PC amount (mg) (X1), PLGA amount (mg) (X2), and surface active agent type (X3) as independent variables, whilst their effect was inspected for entrapment efficiency percent (EE%) (Y1) and particle size (PS) (Y2). Design-Expert® was utilized to choose the optimum PLHNPs for more explorations. The optimum PLHNPs formulation (F2) had EE% of 78.00 ± 0.71 %, PS of 104.50 ± 2.04 nm, polydispersity index of 0.429 ± 0.033, and zeta potential of 23.70 ± 0.10 mV. The optimum PLHNPs formulation was stable for up to 90 days. Moreover, it showed a sustained release profile compared to PN solution. It also showed a spherical shape under a transmission electron microscope. The optimized PN-loaded PLHNPs formulation was radio formulated with radiolabeled isotope ([99mTc]Tc) in maximum radiolabeling yield (91.40 ± 1.85 %) of [99mTc]Tc-PLHNPs to be used in radiological evaluation for in-vivo biodistribution and brain targeting after oral and intranasal administration. [99mTc]Tc-PLHNPs showed higher brain targeting (5.80 ± 0.12 % ID/g) with a high brain-to-blood ratio of (2.42 ± 0.14) at 0.5 h after intranasal administration in addition to controlled blood levels and sustained release up to 8 h that confirm the efficacy of PLHNPs for brain targeting.

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本研究旨在将口服生物利用度较低的β-阻断剂盐酸普萘洛尔(PN)装入PLGA-脂质混合纳米颗粒(PLHNPs)中,以增强其药效。PLHNPs除含有PLGA外,还含有磷脂(PC),可增强PLGA纳米颗粒的鼻内给药潜力,并使PN避开血脑屏障,用于治疗偏头痛。采用单一乳液/溶剂蒸发法制备 PLHNPs,然后以 PC 用量(毫克)(X1)、PLGA 用量(毫克)(X2)和表面活性剂类型(X3)为自变量,应用 23 全因子设计对其进行优化,同时检测它们对夹带效率百分比(EE%)(Y1)和粒度(PS)(Y2)的影响。Design-Expert® 用于选择最佳的 PLHNPs 进行更多探索。最佳 PLHNPs 配方(F2)的 EE% 为 78.00±0.71%,PS 为 104.50±2.04nm,多分散指数为 0.429±0.033,zeta 电位为 23.70±0.10 mV。最佳 PLHNPs 制剂的稳定性可达 90 天。此外,与 PN 溶液相比,PLHNPs 还具有持续释放的特性。在透射电子显微镜下,它还呈现出球形。优化的 PN 负载 PLHNPs 制剂与放射性同位素([99mTc]Tc)进行了放射性配制,[99mTc]Tc-PLHNPs 的放射性标记率最高(91.40±1.85%),可用于口服和鼻内给药后体内生物分布和脑靶向的放射学评估。[99m锝]锝-PLHNPs在鼻内给药后0.5小时显示出更高的脑靶向性(5.80±0.12% ID/g),脑血比高达(2.42±0.14),而且血药浓度可控,持续释放时间长达8小时,这证实了PLHNPs在脑靶向方面的功效。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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