Recent Development of Electrospinning for Drug Delivery, 3rd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (10 August 2023) | Viewed by 15001

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University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre utca 7-9, H-1092 Budapest, Hungary
Interests: polymeric delivery systems; physical ageing of polymers; solid-state characterisation; functionality-related characteristics of polymeric delivery systems; microstructural characterisation of dosage forms; stability tracking of solid dosage forms; regulatory aspects of dosage forms
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School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UK
Interests: 3D printing; bioprinting; drug delivery; electrospinning; medical devices; pharmaceutics; microfluidics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre utca 7-9, H-1092 Budapest, Hungary
Interests: electrospinning; high-speed rotary spinning; solid-state characterisation; industrial feasibility of spinning techniques; pharmaceutical industrial drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Several promising techniques have been developed to overcome the poor solubility and/or membrane permeability properties of new drug candidates, including different fiber formation methods. Electrospinning is one of the most commonly used spinning techniques for fiber formation induced by the high voltage applied to the drug-loaded solution. By modifying the characteristics of the solution and the spinning parameters, the functionality-related properties of the formulated fibers can be finely tuned. The fiber properties (high specific surface area, porosity, and the possibility of controlling the crystalline-amorphous phase transitions of the loaded drugs) result in improved rate and extent of solubility, causing the rapid onset of absorption. However, the enhanced molecular mobility of the amorphous drugs embedded into the fibers is responsible for their physical–chemical instability.

This Special Issue will address new developments in the area of electrospun nanofibers for drug delivery applications, covering the recent advances and future directions of electrospun fiber formulations and scalability.  Moreover, it will highlight and capture the contemporary progress of electrospinning techniques (solution and melt), with particular attention being paid to the industrial feasibility of developing pharmaceutical dosage forms. We invite articles on all aspects of drug-loaded fibrous dosage forms, focusing on the processability, structures and functions, and stability issues based on the regulatory requirements. Original research papers and review articles are welcome.

Prof. Dr. Romána Zelkó
Prof. Dr. Dimitrios A. Lamprou
Dr. István Sebe
Guest Editors

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Keywords

  • electrospinning
  • various electrospinning techniques (combined fiber formation methods)
  • industrial feasibility
  • scale-up possibilities
  • drug delivery systems
  • electrospun scaffolds
  • nanofibers
  • diversity of electrospun fibers
  • biodegradable- and biomass-derived polymers for electrospinning
  • potential drug candidates for nanofibrous dosage forms
  • tunable fibrous drug delivery
  • stability of drug-loaded fibers and dosage forms
  • electrospun drug delivery systems as medical devices and their regulatory approach

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Published Papers (6 papers)

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Research

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22 pages, 3991 KiB  
Article
Influence of Polymer Concentration on Drying of SPION Dispersions by Electrospinning
by Črt Dragar, Žan Rekar, Tanja Potrč, Sebastjan Nemec, Slavko Kralj and Petra Kocbek
Pharmaceutics 2023, 15(6), 1619; https://doi.org/10.3390/pharmaceutics15061619 - 30 May 2023
Viewed by 1397
Abstract
To improve the physical stability of nanoparticle dispersions, several methods for their transformation into stable and easily dispersible dry products have been investigated thus far. Recently, electrospinning was shown to be a novel nanoparticle dispersion drying method, which addresses the crucial challenges of [...] Read more.
To improve the physical stability of nanoparticle dispersions, several methods for their transformation into stable and easily dispersible dry products have been investigated thus far. Recently, electrospinning was shown to be a novel nanoparticle dispersion drying method, which addresses the crucial challenges of the current drying methods. It is a relatively simple method, but it is affected by various ambient, process, and dispersion parameters, which impact the properties of the electrospun product. The aim of this study was, thus, to investigate the influence of the most important dispersion parameter, namely the total polymer concentration, on the drying method efficiency and the properties of the electrospun product. The formulation was based on a mixture of hydrophilic polymers poloxamer 188 and polyethylene oxide in the weight ratio of 1:1, which is acceptable for potential parenteral application. We showed that the total polymer concentration of prior-drying samples is closely related to their viscosity and conductivity, also affecting the morphology of the electrospun product. However, the change in morphology of the electrospun product does not affect the efficiency of SPION reconstitution from the electrospun product. Regardless of the morphology, the electrospun product is not in powder form and is therefore safer to handle compared to powder nanoformulations. The optimal total polymer concentration in the prior-drying SPION dispersion, which enables the formation of an easily dispersible electrospun product with high SPION-loading (65% (w/w)) and fibrillar morphology, was shown to be 4.2% (w/v). Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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17 pages, 4364 KiB  
Article
Formulation and Characterization of Electrospun Nanofibers for Melatonin Ocular Delivery
by Alessia Romeo, Adrienn Kazsoki, Safaa Omer, Balázs Pinke, László Mészáros, Teresa Musumeci and Romána Zelkó
Pharmaceutics 2023, 15(4), 1296; https://doi.org/10.3390/pharmaceutics15041296 - 20 Apr 2023
Cited by 3 | Viewed by 1915
Abstract
The poor ocular bioavailability of melatonin (MEL) limits the therapeutic action the molecule could exert in the treatment of ocular diseases. To date, no study has explored the use of nanofiber-based inserts to prolong ocular surface contact time and improve MEL delivery. Here, [...] Read more.
The poor ocular bioavailability of melatonin (MEL) limits the therapeutic action the molecule could exert in the treatment of ocular diseases. To date, no study has explored the use of nanofiber-based inserts to prolong ocular surface contact time and improve MEL delivery. Here, the electrospinning technique was proposed to prepare poly (vinyl alcohol) (PVA) and poly (lactic acid) (PLA) nanofiber inserts. Both nanofibers were produced with different concentrations of MEL and with or without the addition of Tween® 80. Nanofibers morphology was evaluated by scanning electron microscopy. Thermal and spectroscopic analyses were performed to characterize the state of MEL in the scaffolds. MEL release profiles were observed under simulated physiological conditions (pH 7.4, 37 °C). The swelling behavior was evaluated by a gravimetric method. The results confirmed that submicron-sized nanofibrous structures were obtained with MEL in the amorphous state. Different MEL release rates were achieved depending on the nature of the polymer. Fast (20 min) and complete release was observed for the PVA-based samples, unlike the PLA polymer, which provided slow and controlled MEL release. The addition of Tween® 80 affected the swelling properties of the fibrous structures. Overall, the results suggest that membranes could be an attractive vehicle as a potential alternative to liquid formulations for ocular administration of MEL. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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19 pages, 5616 KiB  
Article
Development of Nanofibers with Embedded Liposomes Containing an Immunomodulatory Drug Using Green Electrospinning
by Luca Casula, Anže Zidar, Julijana Kristl, Matjaž Jeras, Slavko Kralj, Anna Maria Fadda and Špela Zupančič
Pharmaceutics 2023, 15(4), 1245; https://doi.org/10.3390/pharmaceutics15041245 - 14 Apr 2023
Cited by 8 | Viewed by 2251
Abstract
Conventional treatments for chronic wounds are often ineffective, thus new therapeutic approaches are needed, such as the delivery of immunomodulatory drugs that can reduce inflammation, restore immune cell function, and facilitate tissue regeneration. A potential drug for such an approach is simvastatin, which [...] Read more.
Conventional treatments for chronic wounds are often ineffective, thus new therapeutic approaches are needed, such as the delivery of immunomodulatory drugs that can reduce inflammation, restore immune cell function, and facilitate tissue regeneration. A potential drug for such an approach is simvastatin, which has major drawbacks including poor solubility and chemical instability. With the aim of developing a dressing for wound healing, simvastatin and an antioxidant were incorporated into alginate/poly(ethylene oxide) nanofibers by green electrospinning without the use of organic solvents, thanks to their prior encapsulation into liposomes. The composite liposome–nanofiber formulations exhibited fibrillar morphology (160–312 nm) and unprecedentedly high phospholipid and drug content (76%). Transmission electron microscopy revealed dried liposomes as bright ellipsoidal spots homogeneously distributed over the nanofibers. After nanofiber hydration, the liposomes reconstituted in two size populations (~140 and ~435 nm), as revealed by cutting-edge MADLS® analysis. Lastly, in vitro assays demonstrated that composite liposome–nanofiber formulations are superior to liposomal formulations due to a better safety profile in keratinocytes and peripheral blood mononuclear cells. Furthermore, both formulations exhibited similarly advantageous immunomodulatory effects, measured as decreased inflammation in vitro. A synergistic combination of the two nanodelivery systems shows promise for the development of efficient dressings for chronic wound treatment. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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17 pages, 5581 KiB  
Article
Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability
by Edit Hirsch, Márió Nacsa, Eszter Pantea, Edina Szabó, Panna Vass, Júlia Domján, Attila Farkas, Zoltán Nyíri, Zsuzsanna Eke, Tamás Vigh, Sune Klint Andersen, Geert Verreck, György János Marosi and Zsombor Kristóf Nagy
Pharmaceutics 2023, 15(3), 855; https://doi.org/10.3390/pharmaceutics15030855 - 6 Mar 2023
Cited by 2 | Viewed by 2293
Abstract
The aim of this study was to develop antisense oligonucleotide tablet formulations using high-speed electrospinning. Hydroxypropyl-beta-cyclodextrin (HPβCD) was used as a stabilizer and as an electrospinning matrix. In order to optimize the morphology of the fibers, electrospinning of various formulations was carried out [...] Read more.
The aim of this study was to develop antisense oligonucleotide tablet formulations using high-speed electrospinning. Hydroxypropyl-beta-cyclodextrin (HPβCD) was used as a stabilizer and as an electrospinning matrix. In order to optimize the morphology of the fibers, electrospinning of various formulations was carried out using water, methanol/water (1:1), and methanol as solvents. The results showed that using methanol could be advantageous due to the lower viscosity threshold for fiber formation enabling higher potential drug loadings by using less excipient. To increase the productivity of electrospinning, high-speed electrospinning technology was utilized and HPβCD fibers containing 9.1% antisense oligonucleotide were prepared at a rate of ~330 g/h. Furthermore, to increase the drug content of the fibers, a formulation with a 50% drug loading was developed. The fibers had excellent grindability but poor flowability. The ground fibrous powder was mixed with excipients to improve its flowability, which enabled the automatic tableting of the mixture by direct compression. The fibrous HPβCD–antisense oligonucleotide formulations showed no sign of physical or chemical degradation over the 1-year stability study, which also shows the suitability of the HPβCD matrix for the formulation of biopharmaceuticals. The obtained results demonstrate possible solutions for the challenges of electrospinning such as scale-up and downstream processing of the fibers. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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13 pages, 3200 KiB  
Article
Formulation of Levocetirizine-Loaded Core–Shell Type Nanofibrous Orally Dissolving Webs as a Potential Alternative for Immediate Release Dosage Forms
by Adrienn Kazsoki, Barnabás Palcsó, Safaa Mohammed Omer, Zoltan Kovacs and Romána Zelkó
Pharmaceutics 2022, 14(7), 1442; https://doi.org/10.3390/pharmaceutics14071442 - 11 Jul 2022
Cited by 8 | Viewed by 1875
Abstract
Several applications of nanofiber-based systems are based on their corresponding functionality-related properties, which often cannot be satisfied by a fiber web with a monolithic structure because of the various physicochemical properties and amounts of embedded compounds. Therefore, one of the main directions in [...] Read more.
Several applications of nanofiber-based systems are based on their corresponding functionality-related properties, which often cannot be satisfied by a fiber web with a monolithic structure because of the various physicochemical properties and amounts of embedded compounds. Therefore, one of the main directions in the development of fiber systems is creating core–shell type complex fiber structures that can provide application-specific properties to the fiber matrix. The present study aimed to formulate levocetirizine-loaded core–shell type hydrophilic polymer-based fibrous systems. The core phase contained the antihistamine levocetirizine, while the permeation enhancer (Na-taurocholate), the local pH regulator (citric acid), and the cyclodextrin used as a taste masking agent were included in the shell phase of the fibrous formulation. Scanning electron microscopy images indicated that a randomly oriented homogeneous fibrous structure was obtained, while the Raman mapping and chemometric analysis confirmed the partially formed core–shell structure. A fast release rate of the antihistamine drug from the complex structural fibrous system was obtained (within 1 min complete dissolution can be observed) due to its increased surface area to volume ratio and its more favorable wettability properties, which consequently allows for more erosion. The masking properties against the unpleasant bitter taste of API of the formulated complex nanostructure were confirmed by the results of the electronic tongue. The formulated complex nanostructure enabled fast and complete release of the API, providing a potential enhancement in the rate and extent of absorption while masking the unpleasant taste of levocetirizine, which has a high impact on the patient adherence. All in all, the results show that the developed orally dissolving fibrous web formulation can be a potential alternative to the commercially available orally disintegrating tablets. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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Review

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27 pages, 1894 KiB  
Review
Electrospinning of Potential Medical Devices (Wound Dressings, Tissue Engineering Scaffolds, Face Masks) and Their Regulatory Approach
by Luca Éva Uhljar and Rita Ambrus
Pharmaceutics 2023, 15(2), 417; https://doi.org/10.3390/pharmaceutics15020417 - 26 Jan 2023
Cited by 25 | Viewed by 4052
Abstract
Electrospinning is the simplest and most widely used technology for producing ultra-thin fibers. During electrospinning, the high voltage causes a thin jet to be launched from the liquid polymer and then deposited onto the grounded collector. Depending on the type of the fluid, [...] Read more.
Electrospinning is the simplest and most widely used technology for producing ultra-thin fibers. During electrospinning, the high voltage causes a thin jet to be launched from the liquid polymer and then deposited onto the grounded collector. Depending on the type of the fluid, solution and melt electrospinning are distinguished. The morphology and physicochemical properties of the produced fibers depend on many factors, which can be categorized into three groups: process parameters, material properties, and ambient parameters. In the biomedical field, electrospun nanofibers have a wide variety of applications ranging from medication delivery systems to tissue engineering scaffolds and soft electronics. Many of these showed promising results for potential use as medical devices in the future. Medical devices are used to cure, prevent, or diagnose diseases without the presence of any active pharmaceutical ingredients. The regulation of conventional medical devices is strict and carefully controlled; however, it is not yet properly defined in the case of nanotechnology-made devices. This review is divided into two parts. The first part provides an overview on electrospinning through several examples, while the second part focuses on developments in the field of electrospun medical devices. Additionally, the relevant regulatory framework is summarized at the end of this paper. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery, 3rd Edition)
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