Evidence map›Paper›PMID 40617996›Full record

ArticleDrug delivery and translational research2026

Zonisamide nanodiamonds for brain targeting: A comprehensive study utilising in silico, in vitro, in vivo, and molecular investigation for successful nose-to-brain delivery for epilepsy management.

Nihal Mohamed Elmahdy Elsayyad, Omar A Elkady, Mohamed M Swidan, Hassan M Rashed, Tamer M Sakr, Amr M Abdelhamid, Mai A Zaafan, Hanan M El-Laithy

Abstract read
In one paragraph

Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Nihal Mohamed Elmahdy ElsayyadDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), P.O Box 12451, Giza, Egypt.
Omar A ElkadyDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), P.O Box 12451, Giza, Egypt.
Mohamed M SwidanLabeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
Hassan M RashedLabeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
Tamer M SakrRadioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
Amr M AbdelhamidDepartment of Biochemistry and Molecular Biology, Faculty of Pharmacy, October for Modern Sciences and Arts University (MSA), P.O. Box 12451, Giza, Egypt.
Mai A ZaafanDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), P.O. Box 12451, Giza, Egypt.
Hanan M El-LaithyDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), P.O Box 12451, Giza, Egypt. hmellaithy@hotmail.com.ORCID http://orcid.org/0000-0003-4938-2532

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The blood-brain barrier (BBB) is a stringent barrier that restricts the successful brain delivery of polar neurotherapeutics molecules. One such molecule is Zonisamide (ZNS), a hydrophilic centrally acting anti-epileptic drug. This study aims to overcome the poor ZNS BBB permeability using the nose-to-brain (NTB) carbon-based biocompatible nanodiamonds (ND) delivery system to deliver ZNS directly to the brain, bypassing the BBB, thereby enhancing its efficacy and reducing systemic side effects associated with oral ZNS currently available formulation in clinical practice. Intranasal (IN) ND-ZNS formulations were optimised using an Artificial neuronal network (ANN) and assessed for particle size (PS), zeta potential, loading efficiency (%LE), morphology, and in vitro release. The optimum radiolabelled ND-ZNS complex F1 biodistribution in different organs and its pharmacokinetics were compared to oral and IN-free ZNS in mice. Temporal lobe epilepsy (TLE) model in rats was used to compare the anti-epileptic activity of IN ND-ZNS F1 to IN free ZNS by assessing brain activity, epileptic biomarkers such as (brain neuronal specific enolase (NSE), neurofilament light polypeptide (NEFL), and matrix metallopeptidase-9 (MMP-9)), hippocampal histopathology and the modulatory effect on epigenetic miR-199/SIRT-1 and PVT-1/BDNF pathways. Optimized ND-ZNS complex F1 consists of a ZNS:ND ratio of 1:2 and sonicated for 5 min exhibited the least PS (193.7 ± 19.3 nm), adequate %LE (87.1 ± 9.2%) similar to ANN predictions, with a biphasic in vitro release profile of ZNS, beneficial for both acute and chronic epilepsy treatment. The IN delivery of ND-ZNS complex F1 showed preferential higher in vivo brain uptake with minimal systemic exposure linked with higher brain/blood ratio and significant (p ≤ 0.05) overall enhanced pharmacokinetics expressed by C

Indexed as

AnticonvulsantsEpilepsy, Temporal LobeNanodiamondsZonisamideAdministration, IntranasalAnimalsBlood-Brain BarrierBrainDrug Delivery SystemsMaleMiceNasal MucosaRatsRats, Sprague-DawleyTissue DistributionAnticonvulsantsNanodiamondsZonisamideMolecular modellingNanodiamondsNeuronal networksNose-to-brain miR-199Temporal lobe epilepsy modelZonisamide

Identifiers

PMID40617996
PMCPMC13538172

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.