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New Trends in the Controlled Release Systems of Medicinal Substances...
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New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 23366

Special Issue Editors

Dr. Artur Turek

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Guest Editor
Chair and Department of Biopharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Jedności 8, 41-200 Sosnowiec, Poland
Interests: drug technology; pharmacology; medical devices; clinical trials; consumer behavior
Special Issues, Collections and Topics in MDPI journals
Dr. Zhenjia Wang

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA
Interests: drug delivery; cell-based therapy; intravital microscopy; inflammatory diseases and cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to advances in innovative drug delivery systems used in the treatment of central nervous system diseases, i.e., schizophrenia, bipolar affective disorder, depression, dementia, neurodegenerative disorders such as Parkinson’s or Alzheimer’s disease, and brain tumors with special attention to glioblastoma multiforme.

The SI targets the aspect of the delivery of medicinal substances, administration of medicinal products, permeation through the blood–brain barrier, ensuring therapeutic concentration, and the formulation process.

The topics of interest include the following areas:

  • Design and formulation methods of drug delivery systems to brain tissue administration;
  • The mechanisms of drug delivery, drug release patterns, and in vitro–in vivo correlation;
  • Nanoscale brain-targeting drug delivery strategies overcoming the blood–brain barrier;
  • Intracranial drug delivery systems as an independent therapeutic procedure or supporting surgical methods;
  • Current state orally disintegrating tablets used in neurodegenerative diseases;
  • The role of multiple-coated and multi-content formulations in therapy optimization.

I hope that this Special Issue will provide a roadmap for all scientists and practitioners in the treatment of central nervous system diseases.

Dr. Artur Turek
Dr. Zhenjia Wang
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • drug delivery systems
  • brain-targeting drug delivery
  • central nervous system
  • schizophrenia
  • depression
  • Parkinson’s disease
  • Alzheimer’s disease
  • glioblastoma multiforme

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Published Papers (5 papers)

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Research

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12 pages, 2470 KB  
Article
A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates
by Ernesto A. Salegio, Reinier Espinosa, Geary R. Smith, David Shoshan, Matthew Silva, Eli White and Jacob McDonald
Pharmaceutics 2025, 17(9), 1167; https://doi.org/10.3390/pharmaceutics17091167 (registering DOI) - 6 Sep 2025
Abstract
Background: Adeno-associated viral (AAV) vectors are the leading platform for gene therapy, but common delivery routes show limited spread to distal cortical structures, hence the utility of direct, intrathalamic infusions for broader transgene distribution. In this preliminary study, we recapitulate previous studies targeting [...] Read more.
Background: Adeno-associated viral (AAV) vectors are the leading platform for gene therapy, but common delivery routes show limited spread to distal cortical structures, hence the utility of direct, intrathalamic infusions for broader transgene distribution. In this preliminary study, we recapitulate previous studies targeting the thalamus as a conduit to achieve cortical transgene spread and showcase novel data evaluating biodistribution of a green fluorescent protein (GFP) using cryo-fluorescence tomography (CFT). For the first time in nonhuman primates (NHPs) and coupled with magnetic resonance imaging (MRI)-guidance, we demonstrated the application of CFT as a powerful tool to map out vector distribution in the NHP brain. Methods: Briefly, a single thalamic infusion was performed in African green monkeys using ClearPoint’s navigational platform to deliver an AAV serotype 2 vector containing a GFP payload. Transgene biodistribution was assessed in the left and right hemispheres using CFT and histological analysis, respectively. Results: Infusions were successfully performed with sub-millimetric target accuracy and with minimal error, achieving ~86% thalamic coverage with the largest infusion volume. Histology confirmed the presence of the GFP transgene, with the strongest signal in the cerebral gray/white matter and internal capsule, while CFT allowed for the three-dimensional detection of the transgene starting at the site of infusion and spreading to multiple cortical regions. Conclusions: These findings suggest that by combining MRI-guided technology with CFT imaging, it is feasible to map whole-brain gene biodistribution in NHPs. This proof-of-concept study bridges the gap between cellular microscopy and MRI-guidance to provide a complete picture of disease and treatment with clinical applicability. Full article
(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)
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12 pages, 2970 KB  
Article
Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development
by Jon Ander Simón, Emilia Utomo, Félix Pareja, María Collantes, Gemma Quincoces, Aarón Otero, Margarita Ecay, Juan Domínguez-Robles, Eneko Larrañeta and Iván Peñuelas
Pharmaceutics 2023, 15(3), 843; https://doi.org/10.3390/pharmaceutics15030843 - 4 Mar 2023
Cited by 8 | Viewed by 2540
Abstract
The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as [...] Read more.
The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I− took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants. Full article
(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)
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Review

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30 pages, 1149 KB  
Review
Long-Acting Injectable Antipsychotics—A Review on Formulation and In Vitro Dissolution
by Magdalena Markowicz-Piasecka, Marcin Kubisiak, Katarzyna Asendrych-Wicik, Michał Kołodziejczyk, Joanna Grzelińska, Małgorzata Fabijańska and Tomasz Pietrzak
Pharmaceutics 2024, 16(1), 28; https://doi.org/10.3390/pharmaceutics16010028 - 24 Dec 2023
Cited by 21 | Viewed by 14029
Abstract
Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation [...] Read more.
Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation aspects of LAI neuroleptics, with particular emphasis on analysis of drug release profiles as a critical test to guarantee drug quality and relevant therapeutical activity. While there is no officially approved procedure for depot parenteral drug formulations, various dissolution tests which were developed by LAI manufacturers are described. In vitro dissolution tests also possess a critical function in the estimation of the in vivo performance of a drug formulation. For that reason, thorough inspection of the in vitro–in vivo correlation (IVIVC) is also discussed. Full article
(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)
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23 pages, 2617 KB  
Review
Virus-Based Biological Systems as Next-Generation Carriers for the Therapy of Central Nervous System Diseases
by Ilona Nowak, Marcel Madej, Julia Secemska, Robert Sarna and Barbara Strzalka-Mrozik
Pharmaceutics 2023, 15(7), 1931; https://doi.org/10.3390/pharmaceutics15071931 - 11 Jul 2023
Cited by 13 | Viewed by 3645
Abstract
Central nervous system (CNS) diseases are currently a major challenge in medicine. One reason is the presence of the blood–brain barrier, which is a significant limitation for currently used medicinal substances that are characterized by a high molecular weight and a short half-life. [...] Read more.
Central nervous system (CNS) diseases are currently a major challenge in medicine. One reason is the presence of the blood–brain barrier, which is a significant limitation for currently used medicinal substances that are characterized by a high molecular weight and a short half-life. Despite the application of nanotechnology, there is still the problem of targeting and the occurrence of systemic toxicity. Viral vectors and virus-like particles (VLPs) may provide a promising solution to these challenges. Their small size, biocompatibility, ability to carry medicinal substances, and specific targeting of neural cells make them useful in research when formulating a new generation of biological carriers. Additionally, the possibility of genetic modification has the potential for gene therapy. Among the most promising viral vectors are adeno-associated viruses, adenoviruses, and retroviruses. This is due to their natural tropism to neural cells, as well as the possibility of genetic and surface modification. Moreover, VLPs that are devoid of infectious genetic material in favor of increasing capacity are also leading the way for research on new drug delivery systems. The aim of this study is to review the most recent reports on the use of viral vectors and VLPs in the treatment of selected CNS diseases. Full article
(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)
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Other

Jump to: Research, Review

13 pages, 1413 KB  
Systematic Review
The Efficacy of Solanezumab in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Clinical Trials
by Mathias S. Renteros, Renzo Barreto-Abanto, Diego C. Huapaya, Mateo Tovar-Cobos, Richard D. Alvarado-Ramos, Oriana Rivera-Lozada and Joshuan J. Barboza
Pharmaceutics 2025, 17(8), 999; https://doi.org/10.3390/pharmaceutics17080999 - 31 Jul 2025
Viewed by 567
Abstract
Background/Objectives: Solanezumab is a humanized monoclonal antibody designed to bind soluble amyloid-beta (Aβ) and facilitate its clearance from the brain, aiming to slow the progression of Alzheimer’s disease (AD). Methods: A systematic search was applied in four medical databases through October 2024 [...] Read more.
Background/Objectives: Solanezumab is a humanized monoclonal antibody designed to bind soluble amyloid-beta (Aβ) and facilitate its clearance from the brain, aiming to slow the progression of Alzheimer’s disease (AD). Methods: A systematic search was applied in four medical databases through October 2024 to identify phase 2 or 3 randomized controlled trials evaluating solanezumab in patients aged ≥50 years with mild AD or in preclinical stages. The primary outcomes were changes in cognitive and functional scales, including ADAS-cog14, MMSE, ADCS-ADL, and CDR-SB. Data were pooled using a random-effects model, and certainty of evidence was assessed using GRADE. Results: Seven trials involving 4181 participants were included. Solanezumab did not significantly reduce cognitive decline based on ADAS-cog14 (MD = −0.75; 95% CI: −2.65 to 1.15; very low certainty) or improve functional scores on ADCS-ADL (MD = 0.85; 95% CI: −1.86 to 3.56; very low certainty) and CDR-SB (MD = −0.15; 95% CI: −0.89 to 0.60; very low certainty). A modest but statistically significant improvement was observed in MMSE scores (MD = 0.59; 95% CI: 0.33 to 0.86; moderate certainty). Conclusions: While solanezumab may offer slight benefits in general cognitive performance, its overall impact on clinically meaningful outcomes remains limited. The results do not support its use as a disease-modifying therapy for Alzheimer’s disease in either preclinical or symptomatic stages. Full article
(This article belongs to the Special Issue New Trends in the Controlled Release Systems of Medicinal Substances Used in the Treatment of Diseases of the Central Nervous System)
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