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Pharmaceutics
Special Issues
Targeted Drug Delivery: Innovations to Overcome Biological and Technical Barriers
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Targeted Drug Delivery: Innovations to Overcome Biological and Technical Barriers

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

Deadline for manuscript submissions: 20 May 2026 | Viewed by 3581

Special Issue Editors

Dr. Luciana Scotti

E-Mail Website
Guest Editor
Laboratório de Tecnologia Farmacêutica, Federal University of Paraíba, João Pessoa 58051-970, Brazil
Interests: molecular modeling; cheminformatic; natural products
Special Issues, Collections and Topics in MDPI journals
Dr. Marcus Tullius Scotti

E-Mail Website
Guest Editor
Department of Chemistry, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
Interests: QSAR; medicinal chemistry; natural products; cheminformatic
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of drug delivery faces several challenges that stem from the complexity of both human biology and pharmaceutical technology. Target specificity is one of the biggest challenges in ensuring that drugs reach the intended target, such as specific tissues or cells, without affecting other areas of the body. This is especially crucial in treatments like chemotherapy, where non-specific delivery can damage healthy tissues. The challenges in drug delivery discussed in this Special Issue include the following: efficient solutions in the human body and various defense mechanisms, like the blood–brain barrier; stability during storage, transport, and administration, requiring innovative formulations; delivery systems, such as injectables or inhalers that may pose challenges for patients, impacting the efficacy of treatment; developing and manufacturing advanced drug delivery systems, such as nanoparticles or personalized medicine, which can be prohibitively expensive and difficult to scale for widespread use; and drug resistance, which can render delivery systems ineffective.

Researchers are continually innovating to address these challenges, exploring strategies such as nanotechnology, controlled-release systems, and biomimetic approaches in their search for solutions that facilitate more effective and safer drug delivery methods. We look forward to receiving your contributions.

Dr. Luciana Scotti
Dr. Marcus Tullius Scotti
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 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

  • drug delivery
  • biological barriers
  • drug stability
  • patient compliance
  • resistance

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Published Papers (3 papers)

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Research

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23 pages, 13910 KB  
Article
A Hierarchical Microglial-Targeting Nanoplatform for the Therapy of Parkinson’s Disease by Modulating Mitochondrial Dysfunction
by Yue Xing, Shumeng Liu, Yue Na, Hao Wu, Chi Liu, Bohan Zhang, Zhigang Wang, Xiuhong Wu, Ning Zhang and Fang Geng
Pharmaceutics 2026, 18(2), 271; https://doi.org/10.3390/pharmaceutics18020271 - 22 Feb 2026
Viewed by 620
Abstract
Background: Mitochondrial dysfunction in microglia is an important pathogenic factor inducing the onset of Parkinson’s Disease (PD). To address this challenge, a novel hierarchical nano-delivery system was developed to deliver a PD therapeutic agent, wedelolactone (WED) to modulate mitochondrial dysfunction. Methods: [...] Read more.
Background: Mitochondrial dysfunction in microglia is an important pathogenic factor inducing the onset of Parkinson’s Disease (PD). To address this challenge, a novel hierarchical nano-delivery system was developed to deliver a PD therapeutic agent, wedelolactone (WED) to modulate mitochondrial dysfunction. Methods: The nano-delivery system (WED@RBCm-B6&RAP12-NPs) was coated with red blood membrane (RBCm) to avoid immune clearance and conjugated with the BBB-penetrating peptide CGHKAKGPRK (B6) and the microglia targeting peptide EAKIEKHNHYQK (RAP12). Results: The experimental results demonstrated that this novel nano-delivery system could increase its half-life in blood circulation effectively via evading immune recognition and clearance and enhanced its brain distribution by synergistic effect of B6 and RAP12. By specifically targeting microglia in PD mouse brain, the system increased pyruvate dehydrogenase (PDH) activity, leading to mitochondrial structural repair, reduced secretion of pro-inflammatory cytokines, and improved the inflammatory microenvironment. Conclusions: The result first designed and synthesis a dual targeting drug delivery system WED@RBCm-B6&RAP12-NPs which significantly alleviated mitochondrial dysfunction and warranted further study to develop therapeutic agent for PD treatment. Full article
(This article belongs to the Special Issue Targeted Drug Delivery: Innovations to Overcome Biological and Technical Barriers)
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19 pages, 2737 KB  
Article
Chitosan-Coated Liposomes for Intranasal Delivery of Ghrelin: Enhancing Bioavailability to the Central Nervous System
by Cecilia T. de Barros, Thais F. R. Alves, Kessi M. M. Crescencio, Jessica Asami, Moema de A. Hausen, Eliana A. de R. Duek and Marco V. Chaud
Pharmaceutics 2025, 17(11), 1493; https://doi.org/10.3390/pharmaceutics17111493 - 19 Nov 2025
Cited by 1 | Viewed by 1072
Abstract
Background/Objectives: Cachexia is a syndrome characterized by the progressive loss of muscle mass, leading to high morbidity and mortality. Ghrelin (Ghrl) exhibits orexigenic, anabolic, and anti-inflammatory properties with therapeutic potential. However, its low bioavailability limits the efficacy of systemic treatments. This study [...] Read more.
Background/Objectives: Cachexia is a syndrome characterized by the progressive loss of muscle mass, leading to high morbidity and mortality. Ghrelin (Ghrl) exhibits orexigenic, anabolic, and anti-inflammatory properties with therapeutic potential. However, its low bioavailability limits the efficacy of systemic treatments. This study aimed to develop chitosan-coated liposomes containing Ghrl (CH-Lip + Ghrl) for intranasal administration, allowing quantification of Ghrl brain bioavailability using a system optimized for a labile neuropeptide. Methods: The formulation was prepared using thin-film hydration, followed by extrusion and chitosan coating. It was characterized based on morphology, size, zeta potential, stability, encapsulation efficiency, and cell viability. Permeation and mucoadhesion were evaluated ex vivo using porcine nasal mucosa, and cerebral bioavailability was assessed in Wistar rats. Results: CH-Lip + Ghrl had an average of 152.4 ± 0.2 nm (evaluated by DLS), a polydispersity index of 0.159 ± 0.018, a zeta potential of +60.8 ± 6.6 mV, and an encapsulation efficiency of 53.2 ± 0.8%, maintaining stability for 180 days. At 1% (v/v) in culture medium, the formulation retained 73.2 ± 8.4% of the viability in nasal epithelial cells and 81.9 ± 4.8% in neuroblastoma cells. Chitosan coating increased ex vivo mucoadhesion 1.7-fold and permeation 1.3-fold. In vivo, 25 min after intranasal administration, CH-Lip + Ghrl delivered 48.2 ± 8.8% of the dose to the brain, whereas free Ghrl was undetectable. Conclusions: The intranasal administration of CH-Lip + Ghrl enhances cerebral bioavailability of Ghrl. This study integrates a chemically labile neuropeptide with chitosan-coated liposomes for direct brain delivery, representing an innovative platform for future translational studies. Full article
(This article belongs to the Special Issue Targeted Drug Delivery: Innovations to Overcome Biological and Technical Barriers)
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Review

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30 pages, 2344 KB  
Review
Microglia-Targeted Nanotherapeutics in Major Depressive Disorder: An Integrative Perspective on Neuroinflammation and Drug Delivery
by Pablo R. da Silva, Nayana M. M. V. Barbosa, Joandra M. da Silva Leite, Larissa P. Alves, Jéssica C. de Andrade, Allessya L. D. Formiga, Ana Flávia C. Uchôa, Luiza C. D. Neri, Arthur Lins Dias, Adriana M. F. de Oliveira-Golzio, Francisco H. Xavier-Júnior, Ricardo D. de Castro, Cícero F. Bezerra Felipe, Marcus T. Scotti and Luciana Scotti
Pharmaceutics 2026, 18(1), 27; https://doi.org/10.3390/pharmaceutics18010027 - 25 Dec 2025
Viewed by 1222
Abstract
Major depressive disorder (MDD) is a highly prevalent psychiatric condition characterized by complex neurobiological mechanisms, including oxidative stress and neuroinflammation, with microglial activation playing a key role in its pathophysiology. Conventional antidepressants, though widely used, often fail to achieve remission due to limited [...] Read more.
Major depressive disorder (MDD) is a highly prevalent psychiatric condition characterized by complex neurobiological mechanisms, including oxidative stress and neuroinflammation, with microglial activation playing a key role in its pathophysiology. Conventional antidepressants, though widely used, often fail to achieve remission due to limited efficacy, adverse effects, and poor patient adherence. In this context, nanotechnology-based drug delivery systems have emerged as promising strategies to overcome pharmacological limitations, enhance blood–brain barrier (BBB) penetration, and target neuroinflammatory pathways. This narrative review explores the role of microglia as both mediators of neuroinflammation and potential therapeutic targets in MDD. We examine different nanocarriers and their ability to modulate microglial activation, promote a shift from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype, and enhance antidepressant efficacy. Preclinical studies have demonstrated that nanoparticle-based systems not only improve drug bioavailability and brain targeting but also potentiate neuroprotective effects by reducing oxidative stress, promoting neurogenesis, and restoring synaptic plasticity. These findings highlight the potential of nanotechnology as a novel approach to precision neuropsychopharmacology. This review aims to provide an integrative perspective on how nanocarrier-based strategies targeting microglia could redefine future therapeutic paradigms for MDD. Full article
(This article belongs to the Special Issue Targeted Drug Delivery: Innovations to Overcome Biological and Technical Barriers)
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