Nasal Nanotechnology: What Do We Know and What Is Yet to Come?

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

Deadline for manuscript submissions: 31 March 2026 | Viewed by 3712

Special Issue Editors


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Guest Editor
Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95124 Catania, Italy
Interests: drug delivery; nanomedicine; pharmaceutical technology; drug formulation

E-Mail Website
Guest Editor
Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy
Interests: new copolymers to obtain colloidal drug carrier; thermal analysis to study drug-biomembrane models interaction and thermal behavior of drug delivery systems (polymeric and/or lipidic carrier); design, optimization, characterization of nanomedicine for drug delivery; nanomedicine for nose to brain delivery
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Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit original research papers and reviews in the field of nasal drug delivery technology.

This Special Issue is addressed to researchers who are investigating different aspects related to the intranasal administration of drugs and bioactive molecules. It is well known that the nose can be an administration site for different therapeutic purposes: from local treatment to systemic adsorption and to the more recent application for brain targeting, as well as through the olfactory and trigeminal nerve pathways. This strategy allows drugs to reach the brain quickly by evading the BBB, showing a fast onset of action and fewer systemic side effects.

Researchers design formulations with selected raw materials and suitable production processes to obtain specific properties of a final formulation to achieve the above goals. Raw materials (polymers, lipids, surfactants, phospholipids) could be used individually or in combination to produce hybrid systems modified appropriately through functionalization with different molecules (i.e., targeting ligands, cell penetration peptides, etc.). These different strategies provide unique properties to the resulting system in terms of stability in biological fluids, mucoadhesion and controlled drug release.

Both microparticles and/or nanomedicine represent interesting formulation strategies for intranasal delivery. Exploring different aims requires a deep investigation of designed carriers, including specific in vitro evaluations. Ex vivo and in vivo experiments on healthy or disease model animals are used to achieve a proof of concept and are considered as crucial for the acceptance of submitted research papers.

This Special Issue will consider manuscripts dealing with the nasal administration of drug formulations for different therapeutic purposes. Particularly, devices used for nasal administration in preclinical studies represent a growing area of interest for distinguishing internal nasal regions that have been reached.

Original research and review articles are welcome. Research areas may include (but are not limited to) the following: local pathologies such as infectious (caused by viruses, bacteria, fungi, and protozoa) and non-infectious diseases (e.g., caused by allergic and non-allergic, hormonal, and drug-induced reactions); systemic effect (vaccines, lung diseases, etc.); and brain targeting (neurodegenerative diseases, metabolic syndrome, trigeminal pain, headache, etc.).

We look forward to receiving your contributions.

Dr. Rosario Pignatello
Prof. Dr. Teresa Musumeci
Guest Editors

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Keywords

  • nasal drug delivery
  • polymeric and/or lipid nanocarriers
  • rhinitis
  • brain targeting
  • vaccines
  • nose-to-brain drug delivery
  • functionalization
  • ex vivo and in vivo studies
  • cytocompatibility/cytotoxicity
  • mucoadhesion
  • mucosal permeation

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Published Papers (3 papers)

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Research

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13 pages, 1080 KB  
Article
Development of Propofol-Encapsulated Liposomes and the Effect of Intranasal Administration on Bioavailability in Rabbits
by Hitomi Ujita, Hitoshi Higuchi, Yukiko Nishioka, Saki Miyake, Riko Sato and Takuya Miyawaki
Pharmaceutics 2025, 17(11), 1446; https://doi.org/10.3390/pharmaceutics17111446 - 9 Nov 2025
Viewed by 486
Abstract
Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver [...] Read more.
Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiple-comparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. Full article
(This article belongs to the Special Issue Nasal Nanotechnology: What Do We Know and What Is Yet to Come?)
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27 pages, 2871 KB  
Article
Design of Polycation-Functionalized Resveratrol Nanocrystals for Intranasal Administration
by Angela Bonaccorso, Elide Zingale, Giuseppe Caruso, Anna Privitera, Claudia Carbone, Maria Josè Lo Faro, Filippo Caraci, Teresa Musumeci and Rosario Pignatello
Pharmaceutics 2025, 17(10), 1346; https://doi.org/10.3390/pharmaceutics17101346 - 18 Oct 2025
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Abstract
Background/Objectives: Nanocrystals (NCs) are a relatively underexplored yet adaptable platform with broad potential for various applications. Currently, the surface modification of NCs leads to the development of versatile platforms capable of enhancing targeted delivery potential and supporting the advancement of precision medicine. With [...] Read more.
Background/Objectives: Nanocrystals (NCs) are a relatively underexplored yet adaptable platform with broad potential for various applications. Currently, the surface modification of NCs leads to the development of versatile platforms capable of enhancing targeted delivery potential and supporting the advancement of precision medicine. With this in mind, this study focused on the design and surface functionalization of a resveratrol (RSV) NC selected for its antioxidant and neuroprotective effects. Methods: The design of the RSV NC was assessed by the Quality by Design approach. With the aim of intranasal administration, we assessed the RSV NC functionalization with a cationic poly (amino acid) belonging to the class of cell-penetrating peptides. Both naked and surface-modified RSV nanosuspensions were characterized in terms of mucoadhesion, behavior in artificial cerebrospinal fluid, crystallinity, solubility, and storage stability. The scavenging activity (%) of neat RSV and its nanosized forms was measured using the DPPH assay. Results: RSV NCs were successfully designed, producing truncated cubic crystals (~240 nm) with an ~80% drug content. Functionalization was efficiently achieved with poly-l-arginine hydrochloride as revealed by DSC and FTIR and resulted in a positively charged nanosuspension. Nanonization technology improved drug solubility in water and did not affect RSV scavenging activity. Technological characterization demonstrated that both nanosuspensions present suitable properties for intranasal administration in terms of particle size, mucoadhesive tendency, and stability in artificial cerebrospinal fluid. An MTT assay revealed the safety of all treatments in human microglia (HMC3) cells. Conclusions: RSV NCs’ functionalization enhanced their brain delivery potential, establishing a promising platform to improve therapeutic outcomes in neurodegenerative diseases. Full article
(This article belongs to the Special Issue Nasal Nanotechnology: What Do We Know and What Is Yet to Come?)
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Review

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40 pages, 1380 KB  
Review
Recent Advances in Donepezil Delivery Systems via the Nose-to-Brain Pathway
by Jiyoon Jon, Jieun Jeong, Joohee Jung, Hyosun Cho, Kyoung Song, Eun-Sook Kim, Sang Hyup Lee, Eunyoung Han, Woo-Hyun Chung, Aree Moon, Kyu-Tae Kang, Min-Soo Kim and Heejun Park
Pharmaceutics 2025, 17(8), 958; https://doi.org/10.3390/pharmaceutics17080958 - 24 Jul 2025
Cited by 1 | Viewed by 2242
Abstract
Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, [...] Read more.
Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field. Full article
(This article belongs to the Special Issue Nasal Nanotechnology: What Do We Know and What Is Yet to Come?)
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