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Pharmaceutics
Special Issues
CNS Drug Delivery: Recent Advances and Challenges
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CNS Drug Delivery: Recent Advances and Challenges

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 2549

Special Issue Editor

Dr. Daisuke Inoue

E-Mail Website
Guest Editor
Department of Medical Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
Interests: nasal formulation; nasal drug delivery; mucosal absorption; CNS drug delivery; brain drug targeting; neuroinflammation; neuropathic pain; neurodegenerative diseases; sleep cycle; chronopharmacology; circadian rhythm
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The central nervous system (CNS) consists of the brain and spinal cord. It is a critical target for treating various neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, etc. However, physiological barriers, especially the blood-brain barrier (BBB), pose a significant challenge for drug delivery to the CNS, limiting the efficacy of many therapeutic agents.

This Special Issue aims to focus on the latest developments and challenges in CNS drug delivery, including, but not limited to, novel drug delivery systems, nanotechnology, formulations, and targeted drug delivery strategies. We welcome the submission of articles related to CNS drug delivery and invite researchers to publish their original research or review articles.

We look forward to receiving your contributions.

Dr. Daisuke Inoue
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CNS drug delivery
  • blood–brain barrier
  • nanotechnology
  • targeted delivery

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Published Papers (2 papers)

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Research

20 pages, 2425 KB  
Article
Development and Characterization of Heparin–Pullulan Liposomal Nano-Gel for Enhanced Silymarin Delivery in Dementia Therapy: In Vivo Evaluation in Albino Mice
by Aamir Mushtaq, Hamid Saeed Shah, Sairah Hafeez Kamran, Umar Farooq Gohar, Carmen Daniefla Neculoiu, Petru Cezario Podasca, Marius Alexandru Moga and Andrada Camelia Nicolau
Pharmaceutics 2026, 18(3), 348; https://doi.org/10.3390/pharmaceutics18030348 - 11 Mar 2026
Viewed by 235
Abstract
Background/Objectives: Dementia remains one of the major global health challenges of the modern era. Researchers worldwide continue to seek effective therapeutic strategies to combat this neurodegenerative condition. Silymarin is a natural compound with strong neuroprotective and antioxidant properties that holds great potential [...] Read more.
Background/Objectives: Dementia remains one of the major global health challenges of the modern era. Researchers worldwide continue to seek effective therapeutic strategies to combat this neurodegenerative condition. Silymarin is a natural compound with strong neuroprotective and antioxidant properties that holds great potential for dementia management; however, its poor aqueous solubility and limited ability to cross the blood–brain barrier (BBB) have restricted its clinical application. This study focused on the formulation and evaluation of a heparin–pullulan silymarin liposomal (HPSL) nano-gel to enhance the neuroprotective efficacy of silymarin, with potential for improved brain targeting effects. Methods: The HPSL nano-gel was synthesized using the thin-film hydration technique and optimized based on entrapment efficiency, particle size distribution, zeta potential, and in vitro release kinetics. The neuroprotective efficacy of the HPSL nano-gel was evaluated in mice using behavioral evaluations, biochemical quantification of oxidative stress markers, evaluation of cholinergic enzyme activity and detailed histopathological examination of brain tissues. Results: Morphological characterization using scanning electron microscopy (SEM) confirmed a uniform nano-scale structure. The optimized formulation (HPSL-3) exhibited a particle size of 406.07 ± 19.33 nm, zeta potential of −23.72 ± 7.64 mV and an entrapment efficiency of 73.53 ± 12.05%, indicating good colloidal stability and efficient drug loading. The in vitro release profile followed non-Fickian diffusion kinetics, suggesting sustained drug release behavior. Behavioral studies in scopolamine-induced amnesic mice (elevated plus maze, hole board, and light/dark paradigms) demonstrated significant (p ≤ 0.001) improvements in learning and memory retention. Biochemical analyses showed increased levels of ChAT, SOD, CAT, and GSH, along with decreased AChE and MDA levels, supporting the neuroprotective potential of the formulation. Histopathological evaluation revealed marked attenuation of neuronal degeneration, inflammation, and edema (HAI = 4) compared to the scopolamine-treated group (HAI = 11). Conclusions: Overall, the HPSL-2 formulation effectively enhanced silymarin delivery across the BBB, demonstrating potent antioxidant, neuroprotective, and cholinergic modulatory effects. These findings suggest that HPSL-2 represents a promising nano-carrier system for the management of dementia and other oxidative-stress-related neurological disorders. Full article
(This article belongs to the Special Issue CNS Drug Delivery: Recent Advances and Challenges)
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13 pages, 6870 KB  
Article
Intra-Arterial Super-Selective Delivery of Yttrium-90 for the Treatment of Recurrent Glioblastoma: In Silico Proof of Concept with Feasibility and Safety Analysis
by Giulia Paolani, Silvia Minosse, Silvia Strolin, Miriam Santoro, Noemi Pucci, Francesca Di Giuliano, Francesco Garaci, Letizia Oddo, Yosra Toumia, Eugenia Guida, Francesco Riccitelli, Giulia Perilli, Alessandra Vitaliti, Angelico Bedini, Susanna Dolci, Gaio Paradossi, Fabio Domenici, Valerio Da Ros and Lidia Strigari
Pharmaceutics 2025, 17(3), 345; https://doi.org/10.3390/pharmaceutics17030345 - 7 Mar 2025
Cited by 2 | Viewed by 1776
Abstract
Background: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (90Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of [...] Read more.
Background: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (90Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT). Methods: Contrast-enhanced T1-weighted magnetic resonance imaging (T1W-MRI) was used to delineate the tumor volumes and CT scans were used to automatically segment the organs at risk in nine patients with recurrent GBM. Volumetric Modulated Arc Therapy (VMAT) treatment plans were generated using a clinical treatment planning system. Assuming the relative intensity of each voxel from the MR-T1W as a valid surrogate for the post-IACI 90Y-PVA-MB distribution, a specific 90Y dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in a 90Y-PVA-MB-based dose distribution that was then compared with the VMAT plans. Results: The physical dose distribution obtained from the simulation of 1GBq of 90Y-PVA-MBs was rescaled to ensure that 95% of the prescribed dose was delivered to 95% or 99% of the target (i.e., A95% and A99%, respectively). The calculated activities were A95% = 269.2 [63.6–2334.1] MBq and A99% = 370.6 [93.8–3315.2] MBq, while the mean doses to the target were 58.2 [58.0–60.0] Gy for VMAT, and 123.1 [106.9–153.9] Gy and 170.1 [145.9–223.8] Gy for A95% and A99%, respectively. Additionally, non-target brain tissue was spared in the 90Y-PVA-MB treatment compared to the VMAT approach, with a median [range] of mean doses of 12.5 [12.0–23.0] Gy for VMAT, and 0.6 [0.2–1.0] Gy and 0.9 [0.3–1.5] Gy for the 90Y treatments assuming A95% and A99%, respectively. Conclusions: 90Y-PVA-MB IACI using MR-T1W appears to be feasible and safe, as it enables the delivery of higher doses to tumors and lower doses to non-target volumes compared to the VMAT approach. Full article
(This article belongs to the Special Issue CNS Drug Delivery: Recent Advances and Challenges)
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