Advances in Development, Characterisation and Application of Nasal Drug Delivery Systems

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 33150

Special Issue Editor


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Guest Editor
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Interests: nasal drug delivery; nasal powders; spray-drying; nanoparticles; in situ gelling systems; nasal deposition
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Special Issue Information

Dear Colleagues,

Nasal route of administration receives significant scientists’ attention in local and systemic drug delivery, brain targeting and mucosal vaccination. Innovative nasal drug delivery systems are being designed to increase drug availability at the site of action, reduce possible side-effects and improve patient compliance, leading to improved therapy outcome. The anatomy and physiology of the nasal cavity and/or nasal mucosa are recognised as the most critical factors in nasal drug delivery. This indicates the need for advancing and implementation of in vitro/ex vivo characterisation methods enabling the prediction of performance/therapeutic potential of nasal delivery system, and efficiency of delivery to the targeted region of the nasal cavity.

The scope of this special issue is to highlight the latest strategies and approaches in development, characterisation and application of nasal drug delivery systems. Authors are invited to submit their original research or review articles within this subject area.

Prof. Dr. Anita Hafner
Guest Editor

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Keywords

  • nasal drug delivery
  • microparticles
  • nanoparticles
  • nanoemulsions
  • nasal powders
  • in situ gelling systems
  • mucoadhesion
  • permeability
  • biocompatibility
  • cell models
  • nasal deposition
  • nasal delivery device

Published Papers (9 papers)

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Editorial

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3 pages, 166 KiB  
Editorial
Advances in Development, Characterisation and Application of Nasal Drug Delivery Systems
by Anita Hafner
Pharmaceutics 2022, 14(8), 1562; https://doi.org/10.3390/pharmaceutics14081562 - 27 Jul 2022
Cited by 3 | Viewed by 1321
Abstract
Nasal drug administration is being extensively investigated for local and systemic drug delivery, brain targeting and mucosal vaccination [...] Full article

Research

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19 pages, 690 KiB  
Article
Applicability of RPMI 2650 and Calu-3 Cell Models for Evaluation of Nasal Formulations
by Nadica Sibinovska, Simon Žakelj, Jurij Trontelj and Katja Kristan
Pharmaceutics 2022, 14(2), 369; https://doi.org/10.3390/pharmaceutics14020369 - 06 Feb 2022
Cited by 13 | Viewed by 3244
Abstract
The RPMI 2650 and Calu-3 cell lines have been previously evaluated as models of the nasal and airway epithelial barrier, and they have demonstrated the potential to be used in drug permeation studies. However, limited data exist on the utilization of these two [...] Read more.
The RPMI 2650 and Calu-3 cell lines have been previously evaluated as models of the nasal and airway epithelial barrier, and they have demonstrated the potential to be used in drug permeation studies. However, limited data exist on the utilization of these two cell models for the assessment of nasal formulations. In our study, we tested these cell lines for the evaluation of in vitro permeation of intranasally administered drugs having a local and systemic effect from different solution- and suspension-based formulations to observe how the effects of formulations reflect on the measured in vitro drug permeability. Both models were shown to be sufficiently discriminative and able to reveal the effect of formulation compositions on drug permeability, as they demonstrated differences in the in vitro drug permeation comparable to the in vivo bioavailability. Good correlation with the available bioavailability data was also established for a limited number of drugs formulated as intranasal solutions. The investigated cell lines can be applied to the evaluation of in vitro permeation of intranasally administered drugs with a local and systemic effect from solution- and suspension-based formulations. Full article
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15 pages, 2184 KiB  
Article
Evaluation of Ribavirin–Poloxamer Microparticles for Improved Intranasal Absorption
by Dipy M. Vasa, Zainab Bakri, Maureen D. Donovan, Lauren A. O’Donnell and Peter L. D. Wildfong
Pharmaceutics 2021, 13(8), 1126; https://doi.org/10.3390/pharmaceutics13081126 - 23 Jul 2021
Cited by 6 | Viewed by 2635
Abstract
Ribavirin is a water-soluble antiviral compound which, owing to its inability to cross the blood–brain barrier, has limited effectiveness in treating viruses affecting the central nervous system. Direct nose-to-brain delivery was investigated for ribavirin in combination with poloxamer 188, an excipient known to [...] Read more.
Ribavirin is a water-soluble antiviral compound which, owing to its inability to cross the blood–brain barrier, has limited effectiveness in treating viruses affecting the central nervous system. Direct nose-to-brain delivery was investigated for ribavirin in combination with poloxamer 188, an excipient known to enhance the absorption of drug compounds administered intranasally. Composite solid microparticles suitable for intranasal insufflation were prepared by suspending fine crystals of ribavirin in a matrix of poloxamer 188, which were cryogenically milled and characterized to ensure that ribavirin remained stable throughout preparation. In vitro diffusion of ribavirin across a semi-permeable regenerated cellulose membrane showed comparable cumulative drug release after 180 min from both fine solid particles (<20 µm) and 1:1 ribavirin:poloxamer microparticles (d50 = 20 µm); however, the initial release from polymer microparticles was slower, owing to gel formation on the membrane surface. When solid ribavirin was directly deposited on excised olfactory mucosa, either as fine drug particles or 1:1 ribavirin:poloxamer microparticles, permeation was significantly increased from microparticles containing poloxamer 188, suggesting additional interactions between the polymer and olfactory mucosa. These data indicate that for highly water-soluble drugs such as ribavirin or drugs subject to efflux by the nasal mucosa, a formulation of poloxmer-containing microparticles can enhance permeability across the olfactory epithelium and may improve direct nose-to-brain transport. Full article
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17 pages, 2766 KiB  
Article
Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems
by Elka Touitou, Hiba Natsheh, Shatha Boukeileh and Rania Awad
Pharmaceutics 2021, 13(7), 978; https://doi.org/10.3390/pharmaceutics13070978 - 28 Jun 2021
Cited by 7 | Viewed by 2118
Abstract
Nasal nanovesicular delivery systems (NVS) containing the noncontrolled analgesic drugs Ketoprofen, Butorphanol or Tramadol, incorporated in a phospholipid nanovesicular carrier, were designed and investigated. The systems were first characterized for their physicochemical properties. Due to their composition, comprising propylene glycol as a lipid [...] Read more.
Nasal nanovesicular delivery systems (NVS) containing the noncontrolled analgesic drugs Ketoprofen, Butorphanol or Tramadol, incorporated in a phospholipid nanovesicular carrier, were designed and investigated. The systems were first characterized for their physicochemical properties. Due to their composition, comprising propylene glycol as a lipid bilayers fluidizer, these systems contain soft vesicles. Pharmacokinetic profiles of Tramadol in plasma and brain and of Ketoprofen in plasma were also assessed. The analgesic effect of each of the three tested drugs was evaluated in the acetic acid mice model for pain. One important result obtained in this work is that the concentration of Tramadol in rats’ plasma and brain increased rapidly after administration, reaching a peak value 10 min after administration with a Cmax of 2 to 5 folds greater than that for the oral or nasal non-vesicular treatments, respectively. In the case of Ketoprofen, the peak of the drug level in plasma was measured 10 min post nasal administration in NVS. The Cmax was three-fold higher relative to oral administration of this drug. In the experiment testing analgesia, a rapid and improved analgesia was observed for the tested drugs when delivered nasally in the nanocarrier. On the other hand, a weaker analgesic effect was observed for oral and nasal control systems. This new approach suggests that nasal delivery of non-controlled drugs in soft nanovesicles may open the way for better and noninvasive treatment of severe pain. Full article
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12 pages, 2885 KiB  
Article
Comparison of Modern In Vitro Permeability Methods with the Aim of Investigation Nasal Dosage Forms
by Csilla Bartos, Piroska Szabó-Révész, Tamás Horváth, Patrícia Varga and Rita Ambrus
Pharmaceutics 2021, 13(6), 846; https://doi.org/10.3390/pharmaceutics13060846 - 08 Jun 2021
Cited by 11 | Viewed by 3782
Abstract
Nowadays, the intranasal route has become a reliable alternative route for drug administration to the systemic circulation or central nervous system. However, there are no official in vitro diffusion and dissolution tests especially for the investigation of nasal formulations. Our main goal was [...] Read more.
Nowadays, the intranasal route has become a reliable alternative route for drug administration to the systemic circulation or central nervous system. However, there are no official in vitro diffusion and dissolution tests especially for the investigation of nasal formulations. Our main goal was to study and compare a well-known and a lesser-known in vitro permeability investigation method, in order to ascertain which was suitable for the determination of drug permeability through the nasal mucosa from different formulations. The vertical diffusion cell (Franz cell) was compared with the horizontal diffusion model (Side-Bi-Side). Raw and nanonized meloxicam containing nasal dosage forms (spray, gel and powder) were tested and compared. It was found that the Side-Bi-Side cell was suitable for the investigation of spray and powder forms. In contrast, the gel was not measurable on the Side-Bi-Side cell; due to its high viscosity, a uniform distribution of the active substance could not be ensured in the donor phase. The Franz cell, designed for the analysis of semi-solid formulations, was desirable for the investigation of nasal gels. It can be concluded that the application of a horizontal cell is recommended for liquid and solid nasal preparations, while the vertical one should be used for semi-solid formulations. Full article
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30 pages, 3513 KiB  
Article
A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies
by Laura Nižić Nodilo, Ivo Ugrina, Drago Špoljarić, Daniela Amidžić Klarić, Cvijeta Jakobušić Brala, Mirna Perkušić, Ivan Pepić, Jasmina Lovrić, Vesna Saršon, Maša Safundžić Kučuk, Dijana Zadravec, Livije Kalogjera and Anita Hafner
Pharmaceutics 2021, 13(6), 795; https://doi.org/10.3390/pharmaceutics13060795 - 26 May 2021
Cited by 28 | Viewed by 7025
Abstract
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as [...] Read more.
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region. Full article
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14 pages, 2783 KiB  
Article
Nasal Powder Formulations: In-Vitro Characterisation of the Impact of Powders on Nasal Residence Time and Sensory Effects
by Marie Trenkel and Regina Scherließ
Pharmaceutics 2021, 13(3), 385; https://doi.org/10.3390/pharmaceutics13030385 - 13 Mar 2021
Cited by 32 | Viewed by 4018 | Correction
Abstract
Nasal drug delivery is still primarily associated with locally-effective drugs, but next-generation products utilising the benefits of nasal administration—such as easy access to a relatively permeable mucosa, the presence of immunocompetent cells, and a direct route to the brain—are under investigation. Nasal powders [...] Read more.
Nasal drug delivery is still primarily associated with locally-effective drugs, but next-generation products utilising the benefits of nasal administration—such as easy access to a relatively permeable mucosa, the presence of immunocompetent cells, and a direct route to the brain—are under investigation. Nasal powders offer the potential to improve the drugs’ effects by providing higher resistance against the mucociliary clearance, and thus prolonging the contact time of the drug with its target site. However, suitable and easy-to-use in-vitro setups tailored to the characterisation of this effect are missing. In this study, a selection of excipients for powder formulations were used to evaluate the applicability of different methods which investigate the influence on the contact time. The combination of the assessment of rheological properties, dynamic vapour sorption, and adhesiveness on agar–mucin plates was found to be a valuable predictive tool. For the additional assessment of the sensations associated with the close contact of powders and the mucosa, a slug mucosal irritation assay was conducted and adapted to powders. These methods are regarded as being especially useful for comparative screenings in early formulation development. Full article
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Review

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25 pages, 386 KiB  
Review
Can the Nasal Cavity Help Tackle COVID-19?
by Bissera Pilicheva and Radka Boyuklieva
Pharmaceutics 2021, 13(10), 1612; https://doi.org/10.3390/pharmaceutics13101612 - 03 Oct 2021
Cited by 18 | Viewed by 6482
Abstract
Despite the progress made in the fight against the COVID-19 pandemic, it still poses dramatic challenges for scientists around the world. Various approaches are applied, including repurposed medications and alternative routes for administration. Several vaccines have been approved, and many more are under [...] Read more.
Despite the progress made in the fight against the COVID-19 pandemic, it still poses dramatic challenges for scientists around the world. Various approaches are applied, including repurposed medications and alternative routes for administration. Several vaccines have been approved, and many more are under clinical and preclinical investigation. This review aims to systemize the available information and to outline the key therapeutic strategies for COVID-19, based on the nasal route of administration. Full article

Other

3 pages, 521 KiB  
Correction
Correction: Trenkel, M.; Scherließ, R. Nasal Powder Formulations: In-Vitro Characterisation of the Impact of Powders on Nasal Residence Time and Sensory Effects. Pharmaceutics 2021, 13, 385
by Marie Trenkel and Regina Scherließ
Pharmaceutics 2023, 15(7), 1852; https://doi.org/10.3390/pharmaceutics15071852 - 30 Jun 2023
Viewed by 436
Abstract
There was an error in the original publication [...] Full article
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