Intranasal propranolol hydrochloride-loaded PLGA-lipid hybrid nanoparticles for brain targeting: Optimization and biodistribution study by radiobiological evaluation
Rofida Albash , Abdurrahman M. Fahmy , Hesham A. Shamsel-Din , Ahmed B. Ibrahim , Hanin A. Bogari , Rania T. Malatani , Manar Adel Abdelbari , Shaimaa Mosallam
{"title":"Intranasal propranolol hydrochloride-loaded PLGA-lipid hybrid nanoparticles for brain targeting: Optimization and biodistribution study by radiobiological evaluation","authors":"Rofida Albash , Abdurrahman M. Fahmy , Hesham A. Shamsel-Din , Ahmed B. Ibrahim , Hanin A. Bogari , Rania T. Malatani , Manar Adel Abdelbari , Shaimaa Mosallam","doi":"10.1016/j.ejps.2025.107061","DOIUrl":null,"url":null,"abstract":"<div><div>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 2<sup>3</sup> full factorial design using PC amount (mg) (X<sub>1</sub>), PLGA amount (mg) (X<sub>2</sub>), and surface active agent type (X<sub>3</sub>) as independent variables, whilst their effect was inspected for entrapment efficiency percent (EE%) (Y<sub>1</sub>) and particle size (PS) (Y<sub>2</sub>). 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 ([<sup>99m</sup>Tc]Tc) in maximum radiolabeling yield (91.40 ± 1.85 %) of [<sup>99m</sup>Tc]Tc-PLHNPs to be used in radiological evaluation for <em>in-vivo</em> biodistribution and brain targeting after oral and intranasal administration. [<sup>99m</sup>Tc]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.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107061"},"PeriodicalIF":4.3000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098725000600","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
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.