Special Issue "Electrospun and Electrosprayed Formulations for Drug Delivery"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 November 2018)

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Guest Editor
Dr Ian S. Blagbrough

Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
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Interests: electrospinning; electrospraying; biopolymers; coaxial; controlled drug delivery; nanofibre; polymer therapeutics; sustained release; tissue engineering; wound healing; biodegradable; gene therapy; polycaprolactone
Guest Editor
Dr Gareth R. Williams

UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK
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Fax: +44 207 753 5942
Interests: multi-fluid electrospinning; modified release formulations; targeted drug delivery; theranostics; adjuvants

Special Issue Information

Dear Colleagues,

Electrospinning and spraying have been widely explored to prepare drug delivery systems. In this research, it is important to demonstrate the biocompatibility of the electrospun matrices and to investigate the biological activity of the delivered drug or growth factor. The latter must be maintained and the drug delivered in a controlled manner to prepare potent new medicines. Sustained and controlled release of active pharmaceutical ingredients (API) from drug-loaded electrospun matrices can be achieved, with systems composed of biopolymers or biocompatible synthetic polymers found to demonstrate compatibility with human cells as well as significant biological activity.

Investigations of a wide range of polymers and their blends have been undertaken in order to produce advanced materials, potentially displaying superior rheological and viscoelastic properties over other polymers. Different electrospinning techniques allow for the loading of a range of drugs with high encapsulation efficiencies. The potential applications of electrospun nanofibres include drug delivery in research areas as diverse as anti-cancer therapeutics, gene therapy, and wound healing, as post-surgical abdominal anti-adhesion products, and for tissue engineering. Electrospun nanofibres have a large surface area and can mimic the topographical features of extracellular matrices (ECM). Materials with such properties are potentially useful for the much-needed production of bioactive scaffolds, combining the controlled release of a wide variety of therapeutically active agents (e.g. antibiotics, anti-cancer drugs, growth factors, DNA) with a nanofibrous scaffold which will support cell proliferation (e.g. in tissue engineering) or prevent cell migration. With controlled release of the entrapped API and models available both in vitro and in vivo to establish viability in target cells, successful drug delivery can be quantified and cell morphology and pathology assessed, especially aiming for minimal off-target effects.

The simplest electrospun drug delivery system is comprised of only a blend of polymer and drug. However, more advanced materials such as double- and triple-layered fibrous dressings and implants can be produced by electrospinning, representing a significant shift in how we view drug delivery technology.

Despite their great promise, there is more research still to be done before these formulations can be taken forward into the clinic. The controlled release profiles of electrospun matrices and their biocompatibility need to be clearly established.

This special issue of Pharmaceutics has a clear focus on research in these important areas.

Dr Ian S. Blagbrough
Dr Gareth R. Williams
Guest Editors

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Keywords

  • Electrospinning
  • Electrohydrodynamic
  • Controlled release
  • Polymer formulations
  • Biopolymer formulations

Published Papers (10 papers)

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Research

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Open AccessArticle
Enhanced Transepithelial Permeation of Gallic Acid and (−)-Epigallocatechin Gallate across Human Intestinal Caco-2 Cells Using Electrospun Xanthan Nanofibers
Pharmaceutics 2019, 11(4), 155; https://doi.org/10.3390/pharmaceutics11040155
Received: 17 December 2018 / Revised: 17 March 2019 / Accepted: 20 March 2019 / Published: 1 April 2019
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Abstract
Electrospun xanthan polysaccharide nanofibers (X) were developed as an encapsulation and delivery system of the poorly absorbed polyphenol compounds, gallic acid (GA) and (−)-epigallocatechin gallate (EGCG). Scanning electron microscopy was used to characterize the electrospun nanofibers, and controlled release studies were performed at [...] Read more.
Electrospun xanthan polysaccharide nanofibers (X) were developed as an encapsulation and delivery system of the poorly absorbed polyphenol compounds, gallic acid (GA) and (−)-epigallocatechin gallate (EGCG). Scanning electron microscopy was used to characterize the electrospun nanofibers, and controlled release studies were performed at pH 6.5 and 7.4 in saline buffer, suggesting that the release of polyphenols from xanthan nanofibers follows a non-Fickian mechanism. Furthermore, the X-GA and X-EGCG nanofibers were incubated with Caco-2 cells, and the cell viability, transepithelial transport, and permeability properties across cell monolayers were investigated. Increases of GA and EGCG permeabilities were observed when the polyphenols were loaded into xanthan nanofibers, compared to the free compounds. The observed in vitro permeability enhancement of GA and EGCG was induced by the presence of the polysaccharide nanofibers, which successfully inhibited efflux transporters, as well as by opening tight junctions. Full article
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Open AccessArticle
Gold Nanocage-Incorporated Poly(ε-Caprolactone) (PCL) Fibers for Chemophotothermal Synergistic Cancer Therapy
Pharmaceutics 2019, 11(2), 60; https://doi.org/10.3390/pharmaceutics11020060
Received: 29 November 2018 / Revised: 27 December 2018 / Accepted: 28 December 2018 / Published: 1 February 2019
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Abstract
This paper introduces a new fibrous system for synergistic cancer therapy, which consists of gold nanocage (AuNC)-loaded poly(ε-caprolactone) (PCL) fibers with encapsulation of a chemotherapeutic anticancer drug in their core and loading of a phase-changeable fatty acid in their sheath. Under on–off switching [...] Read more.
This paper introduces a new fibrous system for synergistic cancer therapy, which consists of gold nanocage (AuNC)-loaded poly(ε-caprolactone) (PCL) fibers with encapsulation of a chemotherapeutic anticancer drug in their core and loading of a phase-changeable fatty acid in their sheath. Under on–off switching of near-infrared (NIR) light irradiation, the excellent photothermal ability and photostability of AuNCs allows repeated, significant heating of the fibers to a temperature available to hyperthermia. Simultaneously, the NIR light-induced heat generation enables the melting out of the loaded fatty acid, leading to a rapid release of the drug molecules from the fibers. The combination of this NIR light-triggered drug release with the repeated hyperthermia treatment exhibits excellent anticancer efficacy. Full article
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Open AccessArticle
Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment
Pharmaceutics 2019, 11(1), 14; https://doi.org/10.3390/pharmaceutics11010014
Received: 12 November 2018 / Revised: 19 December 2018 / Accepted: 23 December 2018 / Published: 4 January 2019
Cited by 1 | PDF Full-text (2064 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether- [...] Read more.
Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery vehicle for three therapeutic agents with palliative properties for the symptoms of this disease (salicylic acid, methyl salicylate, and capsaicin). For such a task, the production of these nanofibers by means of the electrospinning technique has been optimized. Their morphology and size have been characterized by optical microscopy and scanning electron microscopy (SEM). By selecting the optimal conditions to achieve the smallest and most uniform nanofibers, approximate diameters of up to 800–900 nm were obtained. It was also determined that the therapeutic agents that were used were encapsulated with high efficiency. The analysis of their stability over time by GC-MS showed no significant losses of the encapsulated compounds 15 days after their preparation, except in the case of methyl salicylate. Likewise, it was demonstrated that the therapeutic compounds that were encapsulated conserved, and even improved, their capacity to activate the transient receptor potential cation channel 1 (TRPV1) channel, which has been associated with the formation of psoriatic lesions. Full article
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Open AccessArticle
Fast Dissolving of Ferulic Acid via Electrospun Ternary Amorphous Composites Produced by a Coaxial Process
Pharmaceutics 2018, 10(3), 115; https://doi.org/10.3390/pharmaceutics10030115
Received: 30 May 2018 / Revised: 23 July 2018 / Accepted: 24 July 2018 / Published: 2 August 2018
Cited by 4 | PDF Full-text (3855 KB) | HTML Full-text | XML Full-text
Abstract
Enhancing the dissolution of insoluble active ingredients comprises one of the most important issues in the pharmaceutical and biomaterial fields. Here, a third generation solid dispersion (3rd SD) of ferulic acid was designed and fabricated by a modified coaxial electrospinning process. A traditional [...] Read more.
Enhancing the dissolution of insoluble active ingredients comprises one of the most important issues in the pharmaceutical and biomaterial fields. Here, a third generation solid dispersion (3rd SD) of ferulic acid was designed and fabricated by a modified coaxial electrospinning process. A traditional second generation SD (2nd SD) was also prepared by common one-fluid blending electrospinning and was used as a control. With poly(vinyl alcohol) as the fiber matrix and polyvinylpyrrolidone K10 as an additive in the 3rd SDs, the two electrospinning processes were investigated. The prepared 2nd and 3rd SDs were subjected to a series of characterizations, including X-ray diffraction (XRD), scanning electron microscope (SEM), hydrophilicity and in vitro drug dissolving experiments. The results demonstrate that both SDs were monolithic nanocomposites and that the drugs were amorphously distributed within the matrix. However, the 3rd SDs had better morphology with smaller size, narrower size distribution, and smaller water contact angles than the 2nd SDs. Dissolution tests verified that the 3rd SDs could release their loaded cargoes within 60 s, which was over three times faster than the 2nd SDs. Therefore, a combined strategy based on the modified coaxial electrospinning and the logical selections of drug carriers is demonstrated for creating advanced biomaterials. Full article
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Open AccessArticle
Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation
Pharmaceutics 2018, 10(3), 114; https://doi.org/10.3390/pharmaceutics10030114
Received: 15 June 2018 / Revised: 23 July 2018 / Accepted: 23 July 2018 / Published: 2 August 2018
Cited by 1 | PDF Full-text (5896 KB) | HTML Full-text | XML Full-text
Abstract
Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) [...] Read more.
Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer. Scanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES samples. Different homogenization techniques were compared to maximize homogeneity: mixing in plastic bags and in a high-shear granulator resulting in low-shear mixing (LSM) and high-shear mixing (HSM). Drug content and homogeneity of the tablets were measured by UV-Vis spectrometry, the results revealed acceptably low-dose fluctuations especially with formulations homogenized with HSM. Sieve analysis was used on the final LSM and HSM powder mixtures in order to elucidate the observed differences between tablet homogeneity. Tablets containing drug-loaded electrospun fibers were also studied by Raman mapping demonstrating evenly distributed CAR within the corpus. Full article
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Open AccessArticle
The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers
Pharmaceutics 2018, 10(3), 103; https://doi.org/10.3390/pharmaceutics10030103
Received: 16 March 2018 / Revised: 11 May 2018 / Accepted: 16 May 2018 / Published: 24 July 2018
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Abstract
The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it [...] Read more.
The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it is shown that making drug-loaded Eudragit polymers effectively prevents drug release in low-pH media where the polymer is insoluble, this is not always the case, and other studies have reported significant amounts of drug release at acidic pHs. In this study, we sought to gain insight into the factors influencing the release of active ingredients from Eudragit S100 (ES100) fibers. A family of materials was prepared loaded with the model active ingredients (AIs) benzoic acid, 1-naphthoic acid, 1-naphthylamine, and 9-anthracene carboxylic acid. Analogous systems were prepared with an AI-loaded core and an ES100 sheath. The resultant fibers were smooth and cylindrical in the majority of cases, and X-ray diffraction and differential scanning calorimetry showed them to comprise amorphous solid dispersions. When AI release from the monolithic fibers was probed, it was found that there was significant release at pH 1 in all cases except with 9-anthracene carboxylic acid. Analysis of the results indicated that both the molecular weight of the AI and its acidity/basicity are important in controlling release, with lower molecular weight AIs and basic species released more quickly. The same release trends are seen with the core/shell fibers, but AI release at pH 1 is attenuated. The most significant change between the monolithic and core/shell systems was observed in the case of 1-naphthylamine. Mathematical equations were devised to connect molecular properties and AI release under acidic conditions. Full article
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Review

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Open AccessReview
Electrospun Nanofibers for Tissue Engineering with Drug Loading and Release
Pharmaceutics 2019, 11(4), 182; https://doi.org/10.3390/pharmaceutics11040182
Received: 17 December 2018 / Revised: 3 February 2019 / Accepted: 29 March 2019 / Published: 15 April 2019
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Abstract
Electrospinning technologies have been applied in the field of tissue engineering as materials, with nanoscale-structures and high porosity, can be easily prepared via this method to bio-mimic the natural extracellular matrix (ECM). Tissue engineering aims to fabricate functional biomaterials for the repairment and [...] Read more.
Electrospinning technologies have been applied in the field of tissue engineering as materials, with nanoscale-structures and high porosity, can be easily prepared via this method to bio-mimic the natural extracellular matrix (ECM). Tissue engineering aims to fabricate functional biomaterials for the repairment and regeneration of defective tissue. In addition to the structural simulation for accelerating the repair process and achieving a high-quality regeneration, the combination of biomaterials and bioactive molecules is required for an ideal tissue-engineering scaffold. Due to the diversity in materials and method selection for electrospinning, a great flexibility in drug delivery systems can be achieved. Various drugs including antibiotic agents, vitamins, peptides, and proteins can be incorporated into electrospun scaffolds using different electrospinning techniques and drug-loading methods. This is a review of recent research on electrospun nanofibrous scaffolds for tissue-engineering applications, the development of preparation methods, and the delivery of various bioactive molecules. These studies are based on the fabrication of electrospun biomaterials for the repair of blood vessels, nerve tissues, cartilage, bone defects, and the treatment of aneurysms and skin wounds, as well as their applications related to oral mucosa and dental fields. In these studies, due to the optimal selection of drugs and loading methods based on electrospinning, in vitro and in vivo experiments demonstrated that these scaffolds exhibited desirable effects for the repair and treatment of damaged tissue and, thus, have excellent potential for clinical application. Full article
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Open AccessReview
Engineering of Nanofibrous Amorphous and Crystalline Solid Dispersions for Oral Drug Delivery
Pharmaceutics 2019, 11(1), 7; https://doi.org/10.3390/pharmaceutics11010007
Received: 22 June 2018 / Revised: 12 October 2018 / Accepted: 19 October 2018 / Published: 24 December 2018
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Abstract
Poor aqueous solubility (<0.1 mg/mL) affects a significant number of drugs currently on the market or under development. Several formulation strategies including salt formation, particle size reduction, and solid dispersion approaches have been employed with varied success. In this review, we focus primarily [...] Read more.
Poor aqueous solubility (<0.1 mg/mL) affects a significant number of drugs currently on the market or under development. Several formulation strategies including salt formation, particle size reduction, and solid dispersion approaches have been employed with varied success. In this review, we focus primarily on the emerging trends in the generation of amorphous and micro/nano-crystalline solid dispersions using electrospinning to improve the dissolution rate and in turn the bioavailability of poorly water-soluble drugs. Electrospinning is a simple but versatile process that utilizes electrostatic forces to generate polymeric fibers and has been used for over 100 years to generate synthetic fibers. We discuss the various electrospinning studies and spinneret types that have been used to generate amorphous and crystalline solid dispersions. Full article
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Open AccessReview
Electrospinning of Cyclodextrin Functional Nanofibers for Drug Delivery Applications
Pharmaceutics 2019, 11(1), 6; https://doi.org/10.3390/pharmaceutics11010006
Received: 11 July 2018 / Revised: 17 August 2018 / Accepted: 24 August 2018 / Published: 24 December 2018
Cited by 1 | PDF Full-text (10743 KB) | HTML Full-text | XML Full-text
Abstract
Electrospun nanofibers have sparked tremendous attention in drug delivery since they can offer high specific surface area, tailored release of drugs, controlled surface chemistry for preferred protein adsorption, and tunable porosity. Several functional motifs were incorporated into electrospun nanofibers to greatly expand their [...] Read more.
Electrospun nanofibers have sparked tremendous attention in drug delivery since they can offer high specific surface area, tailored release of drugs, controlled surface chemistry for preferred protein adsorption, and tunable porosity. Several functional motifs were incorporated into electrospun nanofibers to greatly expand their drug loading capacity or to provide the sustained release of the embedded drug molecules. In this regard, cyclodextrins (CyD) are considered as ideal drug carrier molecules as they are natural, edible, and biocompatible compounds with a truncated cone-shape with a relatively hydrophobic cavity interior for complexation with hydrophobic drugs and a hydrophilic exterior to increase the water-solubility of drugs. Further, the formation of CyD-drug inclusion complexes can protect drug molecules from physiological degradation, or elimination and thus increases the stability and bioavailability of drugs, of which the release takes place with time, accompanied by fiber degradation. In this review, we summarize studies related to CyD-functional electrospun nanofibers for drug delivery applications. The review begins with an introductory description of electrospinning; the structure, properties, and toxicology of CyD; and CyD-drug complexation. Thereafter, the release of various drug molecules from CyD-functional electrospun nanofibers is provided in subsequent sections. The review concludes with a summary and outlook on material strategies. Full article
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Open AccessReview
Biomedical Applications of Electrospun Nanofibers: Drug and Nanoparticle Delivery
Pharmaceutics 2019, 11(1), 5; https://doi.org/10.3390/pharmaceutics11010005
Received: 20 September 2018 / Revised: 11 October 2018 / Accepted: 26 October 2018 / Published: 24 December 2018
Cited by 4 | PDF Full-text (1599 KB) | HTML Full-text | XML Full-text
Abstract
The electrospinning process has gained popularity due to its ease of use, simplicity and diverse applications. The properties of electrospun fibers can be controlled by modifying either process variables (e.g., applied voltage, solution flow rate, and distance between charged capillary and collector) or [...] Read more.
The electrospinning process has gained popularity due to its ease of use, simplicity and diverse applications. The properties of electrospun fibers can be controlled by modifying either process variables (e.g., applied voltage, solution flow rate, and distance between charged capillary and collector) or polymeric solution properties (e.g., concentration, molecular weight, viscosity, surface tension, solvent volatility, conductivity, and surface charge density). However, many variables affecting electrospinning are interdependent. An optimized electrospinning process is one in which these parameters remain constant and continuously produce nanofibers consistent in physicochemical properties. In addition, nozzle configurations, such as single nozzle, coaxial, multi-jet electrospinning, have an impact on the fiber characteristics. The polymeric solution could be aqueous, a polymeric melt or an emulsion, which in turn leads to different types of nanofiber formation. Nanofiber properties can also be modified by polarity inversion and by varying the collector design. The active moiety is incorporated into polymeric fibers by blending, surface modification or emulsion formation. The nanofibers can be further modified to deliver multiple drugs, and multilayer polymer coating allows sustained release of the incorporated active moiety. Electrospun nanofibers prepared from polymers are used to deliver antibiotic and anticancer agents, DNA, RNA, proteins and growth factors. This review provides a compilation of studies involving the use of electrospun fibers in biomedical applications with emphasis on nanoparticle-impregnated nanofibers. Full article
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