Nanofibers For Drug Delivery Applications Research Articles

Electrospun nanofibers for drug delivery applications: Methods and mechanism

AbstractElectrospinning procedures such as blend electrospinning, coaxial electrospinning, and emulsion electrospinning have been used for the fabrication of electrospun nanofibers (ENFs) for biomedical applications. These ENFs are attracted great interest especially in drug delivery applications due to their small size, high surface area‐to‐volume, and porosity. The aim of this review is to focus on the controlled release mechanism among the different electrospinning methods, and the selectivity of hydrophilic, water‐soluble polymers as a carrier for drug. The mechanism for the drug delivery depends mainly on the method of drug loading, polymeric interactions, and the nature of polymer swelling, erosion, or degradation. This review compressed on the literature survey about the fabrication of nanofibers by different electrospinning methods, factors affecting the nanofiber morphologies, selectivity of polymeric blends for successful controlled release behavior, and the mechanism involved in the drug release steps.

Electrospun poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan ternary nanofibers with antibacterial activity for treatment of skin infections

In recent years, there is an increasing attention on biocompatible electrospun nanofibers for drug delivery applications since they provide high surface area, controlled and sustained drug release, and they mimic the extracellular matrix. In the present study, tetracycline hydrochloride (TCH) antibiotic loaded poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan nanofibrous membranes were fabricated as a controlled drug delivery system. Poly(ω-pentadecalactone-co-ε-caprolactone) copolymer has been enzymatically synthesized in previous studies, thus it provides an originality to the membrane. Combination of a synthetic polymer, a protein, and a polysaccharide in order to obtain a synergetic effect is another novelty of this work and there exists limited examples for such electrospun membrane. Varied amounts of TCH was electrospun together with poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan (50/40/10 vol ratio) polymer blend (fiber diameters ranged between 85.7–225.2 nm) and several characterizations (morphological and molecular structure, wettability characteristics, and thermal behavior) were applied to examine the drug incorporation. Subsequently, in vitro drug release studies were conducted and mathematical modeling was applied for the detection of transport mechanism of drug. TCH release proceeded 14 days through an initial burst release in first hour and followed by a sustained release. 1% TCH-loaded sample was shown as optimal preparation with 96.5% total drug release and 11.8% initial burst release. TCH-loaded preparations demonstrated a good antibacterial activity against Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria and a limited effect (no inhibition zone observed below 3% TCH concentration) against Gram-negative (Escherichia coli) bacterium. Thus, TCH concentrations of ≥ 3% could be preferred to obtain a wide-spectrum effectiveness. The presented drug delivery system is suggested to be applied for treatment of skin infections as a wound dressing device.

Effects of the Blending Ratio on the Design of Keratin/Poly(butylene succinate) Nanofibers for Drug Delivery Applications.

In recent years there has been a growing interest in the use of proteins as biocompatible and environmentally friendly biomolecules for the design of wound healing and drug delivery systems. Keratin is a fascinating protein, obtainable from several keratinous biomasses such as wool, hair or nails, with intrinsic bioactive properties including stimulatory effects on wound repair and excellent carrier capability. In this work keratin/poly(butylene succinate) blend solutions with functional properties tunable by manipulating the polymer blending ratios were prepared by using 1,1,1,3,3,3-hexafluoroisopropanol as common solvent. Afterwards, these solutions doped with rhodamine B (RhB), were electrospun into blend mats and the drug release mechanism and kinetics as a function of blend composition was studied, in order to understand the potential of such membranes as drug delivery systems. The electrophoresis analysis carried out on keratin revealed that the solvent used does not degrade the protein. Moreover, all the blend solutions showed a non-Newtonian behavior, among which the Keratin/PBS 70/30 and 30/70 ones showed an amplified orientation ability of the polymer chains when subjected to a shear stress. Therefore, the resulting nanofibers showed thinner mean diameters and narrower diameter distributions compared to the Keratin/PBS 50/50 blend solution. The thermal stability and the mechanical properties of the blend electrospun mats improved by increasing the PBS content. Finally, the RhB release rate increased by increasing the keratin content of the mats and the drug diffused as drug-protein complex.

Fabrication and in vitro evaluation of thermally cross-linked gelatin nanofibers for drug delivery applications

In this study, four different nanofibers consisting of gelatin (Gel), doxorubicin (DOX) with gel (DOX@Gel), a composite of gel with poly(ethylene glycol) (PEGylated-gel), and DOX@PEGylated-gel were fabricated. Subsequently, the nanofibers were thermally cross-linked in order to offer a stable and biocompatible alternative for the biological applications of nanofibers such as drug delivery and tissue engineering. Nanofibers were characterized by scanning electron microscopy, Fourier Transform-Infrared Spectroscopy (FT-IR), and confocal microscopy. The formation of smooth, continuous, and uniform nanofibers was observed and the addition of PEG resulted in an increase whereas the incorporation of DOX into nanofibers had no significant change in the diameter of nanofibers. Crosslinking also enlarged the diameter of all nanofibers and the most dramatic increase was observed 53% by DOX@PEGylated-gel. Afterward, the biological performance of the nanofibers was investigated by drug release profile, cytotoxicity on A549 cell line as well as antimicrobial activity with E. coli and S. aureus. The results indicate an enhanced drug release profile, moderate antimicrobial activity, and reasonable cytotoxic efficiency for thermally cross-linked nanofibers compared to uncross-linked nanofibers.

Mechano-Responsive Piezoelectric Nanofiber as an On-Demand Drug Delivery Vehicle.

The control over biodistribution and pharmacokinetics is critical to enhance the efficacy and minimize the side effects of therapeutic agents. To address the need for an on-demand drug delivery system for precise control over the release time and the quantity of drugs, we exploited the mechano-responsiveness of piezoelectric poly(vinylidene fluoride-trifluroethylene) (P(VDF-TrFE)) nanofibers for drug delivery applications. The large surface area-to-volume ratio inherent to nanomaterials, together with the transformative piezoelectric properties, allowed us to use the material as an ultrasensitive and mechano-responsive drug delivery platform driven by the direct piezoelectric effect. The intrinsic negative zeta potential of the nanofibers was utilized to electrostatically load cationic drug molecules, where surface potential changes by exogenous mechanical actuation trigger the release of drug molecules. We show that the drug release kinetics of the P(VDF-TrFE) nanofibers depends on the fiber diameter, thus piezoelectric properties. We further demonstrated that the drug release quantity can be tuned by the applied pressure or dose of physiologically safe corporeal shockwaves as a mechanical stimulus in in vitro and ex vivo models. Overall, we demonstrated the utility of piezoelectric electrospun nanofibers for mechano-responsive controlled drug release.

Drug Delivery Applications of Core-Sheath Nanofibers Prepared by Coaxial Electrospinning: A Review.

Electrospinning has emerged as one of the potential techniques for producing nanofibers. The use of electrospun nanofibers in drug delivery has increased rapidly over recent years due to their valuable properties, which include a large surface area, high porosity, small pore size, superior mechanical properties, and ease of surface modification. A drug loaded nanofiber membrane can be prepared via electrospinning using a model drug and polymer solution; however, the release of the drug from the nanofiber membrane in a safe and controlled way is challenging as a result of the initial burst release. Employing a core-sheath design provides a promising solution for controlling the initial burst release. Numerous studies have reported on the preparation of core-sheath nanofibers by coaxial electrospinning for drug delivery applications. This paper summarizes the physical phenomena, the effects of various parameters in coaxial electrospinning, and the usefulness of core-sheath nanofibers in drug delivery. Furthermore, this report also highlights the future challenges involved in utilizing core-sheath nanofibers for drug delivery applications.

Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy.

Polymeric nanofibers (NFs) have been extensively reported as a biocompatible scaffold to be specifically applied in several researching fields, including biomedical applications. The principal researching lines cover the encapsulation of antitumor drugs for controlled drug delivery applications, scaffolds structures for tissue engineering and regenerative medicine, as well as magnetic or plasmonic hyperthermia to be applied in the reduction of cancer tumors. This makes NFs useful as therapeutic implantable patches or mats to be implemented in numerous biomedical researching fields. In this context, several biocompatible polymers with excellent biocompatibility and biodegradability including poly lactic-co-glycolic acid (PLGA), poly butylcyanoacrylate (PBCA), poly ethylenglycol (PEG), poly (ε-caprolactone) (PCL) or poly lactic acid (PLA) have been widely used for the synthesis of NFs using the electrospun technique. Indeed, other types of polymers with stimuli-responsive capabilities has have recently reported for the fabrication of polymeric NFs scaffolds with relevant biomedical applications. Importantly, colloidal nanoparticles used as nanocarriers and non-biodegradable structures have been also incorporated by electrospinning into polymeric NFs for drug delivery applications and cancer treatments. In this review, we focus on the incorporation of drugs into polymeric NFs for drug delivery and cancer treatment applications. However, the principal novelty compared with previously reported publications is that we also focus on recent investigations concerning new strategies that increase drug delivery and cancer treatments efficiencies, such as the incorporation of colloidal nanoparticles into polymeric NFs, the possibility to fabricate NFs with the capability to respond to external environments, and finally, the synthesis of hybrid polymeric NFs containing carbon nanotubes, magnetic and gold nanoparticles, with magnetic and plasmonic hyperthermia applicability.

Electrospinning Nanofibers for Therapeutics Delivery.

The limitations of conventional therapeutic drugs necessitate the importance of developing novel therapeutics to treat diverse diseases. Conventional drugs have poor blood circulation time and are not stable or compatible with the biological system. Nanomaterials, with their exceptional structural properties, have gained significance as promising materials for the development of novel therapeutics. Nanofibers with unique physiochemical and biological properties have gained significant attention in the field of health care and biomedical research. The choice of a wide variety of materials for nanofiber fabrication, along with the release of therapeutic payload in sustained and controlled release patterns, make nanofibers an ideal material for drug delivery research. Electrospinning is the conventional method for fabricating nanofibers with different morphologies and is often used for the mass production of nanofibers. This review highlights the recent advancements in the use of nanofibers for the delivery of therapeutic drugs, nucleic acids and growth factors. A detailed mechanism for fabricating different types of nanofiber produced from electrospinning, and factors influencing nanofiber generation, are discussed. The insights from this review can provide a thorough understanding of the precise selection of materials used for fabricating nanofibers for specific therapeutic applications and also the importance of nanofibers for drug delivery applications.

Electrospinning of Cyclodextrin Functional Nanofibers for Drug Delivery Applications.

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.

Magnetic nanoparticle-loaded electrospun poly(ε-caprolactone) nanofibers for drug delivery applications

In this study, iron oxide (Fe3O4) magnetic nanoparticles (MNPs) were loaded into poly(e-caprolactone) (PCL) nanofiber mats via electrospinning method and the composite materials were characterized. MNPs were synthesized by a conventional co-precipitation method and treated by oleic acid to obtain hydrophobic nanoparticles. The MNPs were added to PCL solution before electrospinning at varying MNP feed concentrations (1:25, 2:25, 4:25, 8:25, 16:25 and 32:25; weight ratio of MNPs:polymer). The chemical structure of the nanofibrous membranes was investigated by Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM), and analyses by optical and confocal microscopes demonstrated that MNP-loaded PCL nanofibers (MNP@PCL NFs) were homogeneously distributed in the membranes. Fiber diameter changed and bead formation occurred as the concentration of MNPs increased from 1:25 to 32:25. The effect of MNPs concentration on drug loading, the encapsulation efficiency and the release properties of the composite nanofibers was investigated using hydrophilic (Rhodamine-B, RhodB) and hydrophobic (Nile Red, NR) dyes, compared with plain PCL nanofibers. The dyes were used as model drug compounds to simulate drug release from MNP@PCL NFs. The release rate of RhodB from the plain PCL nanofiber mats was faster compared to the composite materials. The results showed that the release of the model molecule was affected by the hydrophilic/hydrophobic character of the drug. MNP@PCL NFs may have the potential for using as localized drug delivery vehicles for tissue engineering applications.

2D imprinted substrates and 3D electrospun scaffolds revolutionize biomedicine.

Momentous advances in engineering in the 1980s and 1990s reduced significantly the manufacturing cost of equipment that can produce nano to low microscale materials. This was a key milestone in the field of biomedicine, as from the early 2000s, we entered the era of nanobiomedicine. Essentially, with very low capital cost, every laboratory in the world could develop cell culture substrates and/or implantable devices with morphological features down to the nanometer scale. The rationale of using such small dimensional features derives from the fact that the extracellular space is comprised of nanoto microscale supramolecular assemblies. Further, cells employ probing filopodia extensions and contractile intracellular machinery to gather topographical, spatial, mechanical and chemical information from the extracellular environment, which consequently determines cell functionality, lineage commitment and fate. Among the various fabrication technologies, lithography constitutes the most popular 2D top-down method, while electrospinning represents the most widely used 3D bottomup method [1–7]. The produced 2D and 3D constructs have enabled the study of cell and tissue responses at previously economical and technological prohibiting small scales and the rational design thereof for a specific application/clinical indication. Key to the design tenant is that topographical features and morphological structures should promote cellular polarization and organized extracellular matrix assembly, resembling the natural conformation of tissues. Using photolithography back in 1983, microscale V-shape grooves were created to study human gingival and porcine epithelial cell response [8]. By 1997, we were in a position to fabricate substrates with feature (square) accuracy down to 14 nm (depth) to study Xenopus neurites outgrowth using electron-beam lithography [9,10]. To date, we have successfully imprinted various gratings and geometric shapes along different scales onto thermoplastic polymers to create biologically relevant topographical interfaces. Data obtained from these and other studies clearly illustrate that topographical features are powerful modulators of cell morphology and differential function [11–15]. Further, nanoand microscale arrays have been shown to be potent tools in maintaining the phenotype fidelity of permanently differentiated cells and in differentiating stem cells toward specific lineages [16,17]. Multiple topographic arrays have also been used as high-throughput systems to elucidate the cell–surface interactions and enable identification of improved surfaces for optimal/required cell response [18,19]. Specifically, topographical features have been shown to directly modulate cell–material interaction and to affect the composition, orientation and conformation of adsorbed extracellular matrix components [20,21]. Further, nanoimprinted materials have been shown to either 2D imprinted substrates and 3D electrospun scaffolds revolutionize biomedicine

Functionalization Techniques for Electrospun Nanofibers for Drug Delivery Applications: A Review

Functionalization Techniques for Electrospun Nanofibers for Drug Delivery Applications: A Review

Drug loading and release from electrospun biodegradable nanofibers.

This review explores the potential of electrospun nanofibers for drug delivery applications. In the first section, some of the key challenges in drug delivery as well as the promise of electrospun drug loaded nanofibers are highlighted. Techniques of drug incorporation into nanofibers such as blending, surface modification and co-axial electrospinning are detailed. The major requirements of drug eluting scaffolds such as biocompatibility and biodegradability, efficient drug control and release, and adequate mechanical performance are addressed. Drug release kinetics, biodegradability and mechanical properties can be controlled by careful selection of polymers and electrospinning processing parameters while biocompatibility of electrospun mats may be enhanced through surface modification of the nanofibers. The major applications as well as the routes of administration of the drug-loaded electrospun nanostructures are discussed. Currently available drug eluting nanofibrous mats for applications ranging from cancer therapy to wound dressings as well as their preclinical trials are also reviewed.

A Review of the Effect of Processing Variables on the Fabrication of Electrospun Nanofibers for Drug Delivery Applications

Electrospinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nanotechnology that sparked worldwide research interest in nanomaterials for their preparation and application in biomedicine and drug delivery. Electrospinning is a simple, adaptable, cost-effective, and versatile technique for producing nanofibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nanofibers. The nanofiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nanofiber fabrication by electrospinning has broadened the horizons for widespread application of nanofibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electrospun nanofibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of postsurgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electrospun nanofibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nanofibers when applied to drug delivery.

OA02.16. Ayurvedic nanomaterials: Preparation and characterization of ginger loaded polymeric nanofibers for drug delivery applications

Purpose:The purpose of this study is to combine nanotechnology and ayurveda to develop novel ayurvedic nano materials with enhanced functionalities towards betterment of the clinical practices. In this context, we have fabricated ginger loaded polymeric nano fibers. Ginger is an important ayurvedic material because it exhibits a wide range of biological and pharmacological activities including antioxidant, antiinflammatory, antibacterial, antifungal, antiparasitic, anticancer and detoxifying properties. Incorporation of ginger with polymeric materials enables high-performance drug delivery systems.Method:Nano fibers are produced by electro spinning method using poly(methyl methacrylate) (PMMA) and gelatin polymers. Electro spinning is a simple and versatile method for fabrication of nano fibers with high surface to volume ratio. The electro spinning parameters are optimized with respect to flow rate, voltage between the two electrodes, tip collector distance to obtain fine nano fibers without beads. After optimization, ginger loaded nano fibers are fabricated by mixing ginger with polymer before electro spinning.Result:The fibers were characterized by various techniques such as optical microscope, Fourier transform infrared spectroscope (FTIR), UVVis spectroscope, atomic force microscope (AFM) and high resolution transmission electron microscope (HRTEM). The studies showed uniform and smooth fibers (hollow fibers) loaded with ginger. The average diameter of the nano fibers is in the range of 100 to 600 nm. The UVVis studies showed the release of the drugs with respect to time depending on the morphology of the fiber and medium.Conclusion:Ginger loaded nano fibers are successfully fabricated with smooth surface without beads. The ginger release studies demonstrated a slow release of ginger from the nano fibers. The results demonstrate that the ginger loaded nano fiber could be a good candidate to manage various diseases, specifically, rheumatic diseases, joint pains and migraine. This work provides an opportunity to expand the medical benefits of combined nanotechnology and ayurveda.