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Pharmaceutics
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Recent Development of Electrospinning for Drug Delivery Volume II
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Recent Development of Electrospinning for Drug Delivery Volume II

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 38208

Special Issue Editors

Prof. Dr. Romána Zelkó

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Guest Editor
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
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Dimitrios A. Lamprou

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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
Dr. István Sebe

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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. With 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) enable the improved rate and extent of solubility, causing a 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 recent advantages and future directions on electrospun fiber formulations and scalability.  Moreover, it serves to highlight and capture the contemporary progress of electrospinning techniques (solution and melt), with particular attention 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

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

  • 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

Related Special Issues

Published Papers (10 papers)

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Research

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19 pages, 2239 KiB  
Article
Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application
by Gillian D. Mahumane, Pradeep Kumar, Viness Pillay and Yahya E. Choonara
Pharmaceutics 2020, 12(10), 934; https://doi.org/10.3390/pharmaceutics12100934 - 30 Sep 2020
Cited by 15 | Viewed by 4308
Abstract
Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have [...] Read more.
Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72–542 nm and 124–592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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20 pages, 4272 KiB  
Article
Electrospun Bioactive Wound Dressing Containing Colloidal Dispersions of Birch Bark Dry Extract
by Francis Kamau Mwiiri, Johanna M. Brandner and Rolf Daniels
Pharmaceutics 2020, 12(8), 770; https://doi.org/10.3390/pharmaceutics12080770 - 14 Aug 2020
Cited by 19 | Viewed by 3270
Abstract
Novel birch bark dry extract (TE)-loaded polyvinyl alcohol (PVA) fiber mats intended for wound therapy were developed through an electrospinning process. Colloidal dispersions containing TE as the active substance were prepared by the high-pressure homogenization (HPH) technique using hydrogenated phospholipids as stabilizer. Subsequently, [...] Read more.
Novel birch bark dry extract (TE)-loaded polyvinyl alcohol (PVA) fiber mats intended for wound therapy were developed through an electrospinning process. Colloidal dispersions containing TE as the active substance were prepared by the high-pressure homogenization (HPH) technique using hydrogenated phospholipids as stabilizer. Subsequently, the colloidal dispersions were blended with aqueous PVA solutions in the ratio of 60:40 (wt.%) and electrospun to form the nanofiber mats. Fiber morphology examined using scanning electron microscopy (SEM) indicated that fibers were uniform and achieved diameters in the size range of 300–1586 nm. Confocal Raman spectral imaging gave good evidence that triterpenes were encapsulated within the electrospun mats. In vitro drug release and ex vivo permeation studies indicated that the electrospun nanofibers showed a sustained release of betulin, the main component of birch bark dry extract, making the examined dressings highly applicable for several wound care applications. Ex vivo wound healing studies proved that electrospun fiber mats containing TE accelerated wound healing significantly more than TE oleogel, which was comparable to an authorized product that consists of TE and sunflower oil and has proved to enhance wound healing. Therefore, our results conclude that the developed TE-PVA-based dressings show promising potential for wound therapy, an area where effective remedy is needed. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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20 pages, 9698 KiB  
Article
Hydrolytic Degradability, Cell Tolerance and On-Demand Antibacterial Effect of Electrospun Photodynamically Active Fibres
by Amy Contreras, Michael J. Raxworthy, Simon Wood and Giuseppe Tronci
Pharmaceutics 2020, 12(8), 711; https://doi.org/10.3390/pharmaceutics12080711 - 29 Jul 2020
Cited by 10 | Viewed by 3105
Abstract
Photodynamically active fibres (PAFs) are a novel class of stimulus-sensitive systems capable of triggering antibiotic-free antibacterial effect on-demand when exposed to light. Despite their relevance in infection control, however, the broad clinical applicability of PAFs has not yet been fully realised due to [...] Read more.
Photodynamically active fibres (PAFs) are a novel class of stimulus-sensitive systems capable of triggering antibiotic-free antibacterial effect on-demand when exposed to light. Despite their relevance in infection control, however, the broad clinical applicability of PAFs has not yet been fully realised due to the limited control in fibrous microstructure, cell tolerance and antibacterial activity in the physiologic environment. We addressed this challenge by creating semicrystalline electrospun fibres with varying content of poly[(l-lactide)-co-(glycolide)] (PLGA), poly(ε-caprolactone) (PCL) and methylene blue (MB), whereby the effect of polymer morphology, fibre composition and photosensitiser (PS) uptake on wet state fibre behaviour and functions was studied. The presence of crystalline domains and PS–polymer secondary interactions proved key to accomplishing long-lasting fibrous microstructure, controlled mass loss and controlled MB release profiles (37 °C, pH 7.4, 8 weeks). PAFs with equivalent PLGA:PCL weight ratio successfully promoted attachment and proliferation of L929 cells over a 7-day culture with and without light activation, while triggering up to 2.5 and 4 log reduction in E. coli and S. mutans viability, respectively. These results support the therapeutic applicability of PAFs for frequently encountered bacterial infections, opening up new opportunities in photodynamic fibrous systems with integrated wound healing and infection control capabilities. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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10 pages, 2243 KiB  
Article
Preparation and Characterization of Fenofibrate-Loaded PVP Electrospun Microfibrous Sheets
by Emese Sipos, Tamás Csatári, Adrienn Kazsoki, Attila Gergely, Enikő Bitay, Zoltán-István Szabó and Romána Zelkó
Pharmaceutics 2020, 12(7), 612; https://doi.org/10.3390/pharmaceutics12070612 - 30 Jun 2020
Cited by 9 | Viewed by 2479
Abstract
Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including [...] Read more.
Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including attenuated total reflectance Fourier-transformed infrared spectroscopy and positron annihilation lifetime spectroscopy, while fiber morphology was monitored via scanning electron microscopy. Dissolution studies carried out both in 0.025 M sodium dodecyl sulfate and in water revealed an immediate release of the active agent, with an approximately 40-fold release rate enhancement in water when compared to the micronized active agent. The dramatic increase in dissolution was attributed partially to the amorphous form of the originally crystalline active agent and the rapid disintegration of the electrospun microfibrous sheet due to its high surface area and porosity. The obtained results could pave the way for a formulation of the frequently used antihyperlipidemic agent with increased bioavailability. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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16 pages, 3745 KiB  
Article
Electrospun Resveratrol-Loaded Polyvinylpyrrolidone/Cyclodextrin Nanofibers and Their Biomedical Applications
by Ying-Cheng Lin, Stephen Chu-Sung Hu, Pao-Hsien Huang, Tzu-Ching Lin and Feng-Lin Yen
Pharmaceutics 2020, 12(6), 552; https://doi.org/10.3390/pharmaceutics12060552 - 13 Jun 2020
Cited by 39 | Viewed by 3479
Abstract
Resveratrol is a naturally occurring polyphenol compound which has been shown to possess antioxidant and anti-inflammatory properties. However, its pharmaceutical applications are limited by its poor water solubility. In this study, we used electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin [...] Read more.
Resveratrol is a naturally occurring polyphenol compound which has been shown to possess antioxidant and anti-inflammatory properties. However, its pharmaceutical applications are limited by its poor water solubility. In this study, we used electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin (HPBCD) loaded with resveratrol. We used X-ray diffractometry to analyze crystalline structure, Fourier transform infrared spectroscopy to determine intermolecular hydrogen bonding, antioxidant assays to measure antioxidant activity, and Franz diffusion cells to evaluate skin penetration. Our results showed that the aqueous solubility of resveratrol nanofibers was greatly improved (by more than 20,000-fold) compared to the pure compound. Analysis of physicochemical properties demonstrated that following nanofiber formation, resveratrol was converted from a crystalline to amorphous structure, and resveratrol formed new intermolecular bonds with PVP and HPBCD. Moreover, resveratrol nanofibers showed good antioxidant activity. In addition, the skin penetration ability of resveratrol in the nanofiber formulation was greater than that of pure resveratrol. Furthermore, resveratrol nanofibers suppressed particulate matter (PM)-induced expression of inflammatory proteins (COX-2 and MMP-9) in HaCaT keratinocytes. Therefore, resveratrol-loaded nanofibers can effectively improve the solubility and physicochemical properties of resveratrol, and may have potential applications as an antioxidant and anti-inflammatory formulation for topical skin application. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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16 pages, 3836 KiB  
Article
Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers
by Andrea Kovács, Adrienn Kazsoki, Balázs Démuth, Bernadett Szirányi, János Madarász, Károly Süvegh and Romána Zelkó
Pharmaceutics 2020, 12(4), 385; https://doi.org/10.3390/pharmaceutics12040385 - 23 Apr 2020
Cited by 3 | Viewed by 2364
Abstract
Electrospun nanofibers were prepared from furosemide-containing hydroxypropyl cellulose and poly(vinylpyrrolidone) aqueous solutions using different solubility enhancers. In one case, a solubilizer, triethanolamine, was applied, while in the other case a pH-modifier, sodium hydroxide, was applied. Scanning electron microscopy (SEM) was carried out for [...] Read more.
Electrospun nanofibers were prepared from furosemide-containing hydroxypropyl cellulose and poly(vinylpyrrolidone) aqueous solutions using different solubility enhancers. In one case, a solubilizer, triethanolamine, was applied, while in the other case a pH-modifier, sodium hydroxide, was applied. Scanning electron microscopy (SEM) was carried out for morphological characterization of the fibers. The SEM images indicated similar mean diameter size of the two fibrous formulations. However, in contrast to the NaOH-containing fibers of normal diameter distribution, the triethanolamine-containing fibers showed approximately normal diameter distribution, possibly due to their plasticizing effect and the consequent slightly ribbon-like morphology. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffraction (XRD) and positron annihilation lifetime spectroscopy (PALS) were applied for microstructural characterization. The FTIR measurements confirmed that furosemide salt was formed in both cases. There was no sign of any crystallinity based on the XRD measurements. However, the PALS highlighted the differences in the average o-Ps lifetime values and distributions of the furosemide-loaded fibrous formulations. The two types of electrospun nanofibrous formulations containing amorphous furosemide salt showed similar macrostructures but different microstructural characteristics depending on the type of solubility enhancers, which lead to altered storage stability. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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11 pages, 3006 KiB  
Article
The Effect of Solvent Vapor Annealing on Drug-Loaded Electrospun Polymer Fibers
by Yu-Jing Chiu, Ziwei Zhang, Karolina Dziemidowicz, Christos-Georgios Nikoletopoulos, Ukrit Angkawinitwong, Jiun-Tai Chen and Gareth R. Williams
Pharmaceutics 2020, 12(2), 139; https://doi.org/10.3390/pharmaceutics12020139 - 06 Feb 2020
Cited by 13 | Viewed by 3126
Abstract
Electrospinning has emerged as a powerful strategy to develop controlled release drug delivery systems but the effects of post-fabrication solvent vapor annealing on drug-loaded electrospun fibers have not been explored to date. In this work, electrospun poly(ε-caprolactone) (PCL) fibers loaded with the hydrophobic [...] Read more.
Electrospinning has emerged as a powerful strategy to develop controlled release drug delivery systems but the effects of post-fabrication solvent vapor annealing on drug-loaded electrospun fibers have not been explored to date. In this work, electrospun poly(ε-caprolactone) (PCL) fibers loaded with the hydrophobic small-molecule spironolactone (SPL) were explored. Immediately after fabrication, the fibers are smooth and cylindrical. However, during storage the PCL crystallinity in the fibers is observed to increase, demonstrating a lack of stability. When freshly-prepared fibers are annealed with acetone vapor, the amorphous PCL chains recrystallize, resulting in the fiber surfaces becoming wrinkled and yielding shish-kebab like structures. This effect does not arise after the fibers have been aged. SPL is found to be amorphously dispersed in the PCL matrix both immediately after electrospinning and after annealing. In vitro dissolution studies revealed that while the fresh fibers show a rapid burst of SPL release, after annealing more extended release profiles are observed. Both the rate and extent of release can be varied through changing the annealing time. Further, the annealed formulations are shown to be stable upon storage. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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Review

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21 pages, 423 KiB  
Review
Scale-up of Electrospinning: Market Overview of Products and Devices for Pharmaceutical and Biomedical Purposes
by Safaa Omer, László Forgách, Romána Zelkó and István Sebe
Pharmaceutics 2021, 13(2), 286; https://doi.org/10.3390/pharmaceutics13020286 - 22 Feb 2021
Cited by 104 | Viewed by 5314
Abstract
Recently, the electrospinning (ES) process has been extensively studied due to its potential applications in various fields, particularly pharmaceutical and biomedical purposes. The production rate using typical ES technology is usually around 0.01–1 g/h, which is lower than pharmaceutical industry production requirements. Therefore, [...] Read more.
Recently, the electrospinning (ES) process has been extensively studied due to its potential applications in various fields, particularly pharmaceutical and biomedical purposes. The production rate using typical ES technology is usually around 0.01–1 g/h, which is lower than pharmaceutical industry production requirements. Therefore, different companies have worked to develop electrospinning equipment, technological solutions, and electrospun materials into large-scale production. Different approaches have been explored to scale-up the production mainly by increasing the nanofiber jet through multiple needles, free-surface technologies, and hybrid methods that use an additional energy source. Among them, needleless and centrifugal methods have gained the most attention and applications. Besides, the production rate reached (450 g/h in some cases) makes these methods feasible in the pharmaceutical industry. The present study overviews and compares the most recent ES approaches successfully developed for nanofibers’ large-scale production and accompanying challenges with some examples of applied approaches in drug delivery systems. Besides, various types of commercial products and devices released to the markets have been mentioned. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
49 pages, 7703 KiB  
Review
An Overview of Biopolymeric Electrospun Nanofibers Based on Polysaccharides for Wound Healing Management
by Andreea-Teodora Iacob, Maria Drăgan, Oana-Maria Ionescu, Lenuța Profire, Anton Ficai, Ecaterina Andronescu, Luminița Georgeta Confederat and Dan Lupașcu
Pharmaceutics 2020, 12(10), 983; https://doi.org/10.3390/pharmaceutics12100983 - 17 Oct 2020
Cited by 108 | Viewed by 7571
Abstract
Currently, despite the thoroughgoing scientific research carried out in the area of wound healing management, the treatment of skin injuries, regardless of etiology remains a big provocation for health care professionals. An optimal wound dressing should be nontoxic, non-adherent, non-allergenic, should also maintain [...] Read more.
Currently, despite the thoroughgoing scientific research carried out in the area of wound healing management, the treatment of skin injuries, regardless of etiology remains a big provocation for health care professionals. An optimal wound dressing should be nontoxic, non-adherent, non-allergenic, should also maintain a humid medium at the wound interfacing, and be easily removed without trauma. For the development of functional and bioactive dressings, they must meet different conditions such as: The ability to remove excess exudates, to allow gaseous interchange, to behave as a barrier to microbes and to external physical or chemical aggressions, and at the same time to have the capacity of promoting the process of healing by stimulating other intricate processes such as differentiation, cell adhesion, and proliferation. Over the past several years, various types of wound dressings including hydrogels, hydrocolloids, films, foams, sponges, and micro/nanofibers have been formulated, and among them, the electrospun nanofibrous mats received an increased interest from researchers due to the numerous advantages and their intrinsic properties. The drug-embedded nanofibers are the potential candidates for wound dressing application by virtue of: Superior surface area-to volume ratio, enormous porosity (can allow oxy-permeability) or reticular nano-porosity (can inhibit the microorganisms’adhesion), structural similitude to the skin extracellular matrix, and progressive electrospinning methodology, which promotes a prolonged drug release. The reason that we chose to review the formulation of electrospun nanofibers based on polysaccharides as dressings useful in wound healing was based on the ever-growing research in this field, research that highlighted many advantages of the nanofibrillary network, but also a marked versatility in terms of numerous active substances that can be incorporated for rapid and infection-free tissue regeneration. In this review, we have extensively discussed the recent advancements performed on electrospun nanofibers (eNFs) formulation methodology as wound dressings, and we focused as well on the entrapment of different active biomolecules that have been incorporated on polysaccharides-based nanofibers, highlighting those bioagents capable of improving the healing process. In addition, in vivo tests performed to support their increased efficacy were also listed, and the advantages of the polysaccharide nanofiber-based wound dressings compared to the traditional ones were emphasized. Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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1 pages, 157 KiB  
Erratum
Erratum: Mwiiri, F.K.; et al. Electrospun Bioactive Wound Dressing Containing Colloidal Dispersions of Birch Bark Dry Extract. Pharmaceutics 2020, 12, 770
by Francis Kamau Mwiiri, Johanna M. Brandner and Rolf Daniels
Pharmaceutics 2020, 12(10), 991; https://doi.org/10.3390/pharmaceutics12100991 - 19 Oct 2020
Cited by 2 | Viewed by 1530
Abstract
The authors wish to make the following correction to this paper [...] Full article
(This article belongs to the Special Issue Recent Development of Electrospinning for Drug Delivery Volume II)
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