Therapeutic applications of electrospun nanofibers for drug delivery systems

Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release.     

Delivering bioactive molecules as instructive cues to engineered tissues

INTRODUCTION: Growth factors and other bioactive molecules play a crucial role in the creation of functional engineered tissues from dissociated cells. AREAS COVERED: This review discusses the delivery of bioactive molecules - particularly growth factors - to affect cellular function in the context of tissue engineering. We discuss the primary biological themes that are addressed by delivering bioactives, the types of molecules that are to be delivered, the major materials used in producing scaffolds and/or drug delivery systems, and the principal drug delivery strategies. EXPERT OPINION: Drug delivery systems have allowed the sustained release of bioactive molecules to engineered tissues, with marked effects on tissue function. Sophisticated drug delivery techniques will allow precise recapitulation of developmental milestones by providing temporally distinct patterns of release of multiple bioactives. High-resolution patterning techniques will allow tissue constructs to be designed with precisely defined areas where bioactives can act. New biological discoveries, just as the development of small molecules with potent effects on cell differentiation, will likely have a marked impact on the field.     

Emerging frontiers in drug release control by core–shell nanofibers: a review

Abstract

In recent years, core–shell (CS) nanofiber has widely been used as a carrier for controlled drug release. This outstanding attention toward CS nanofiber is mainly due to its tremendous significance in controllable drug release in specific locations. The major advantage of CS nanofibers is forming a highly porous mesh, boosting its performance for many applications, due to its large surface-to-volume ratio. This inherently high ratio has prompted electrospun fibers to be considered one of the best drug-delivery-systems available, with the capacity to enhance properties such as cell attachment, drug loading, and mass transfer. Using electrospun fibers as CS nanofibers to incorporate different cargos such as antibiotics, anticancer agents, proteins, DNA, RNA, living cells, and diverse growth factors would considerably satisfy the need for a universal carrier in the field of nanotechnology. In addition to their high surface area, other benefit included in these nanofibers is the ability to trap drugs, easily controlled morphology, and their biomimetic characteristics. In this review, by taking the best advantages of the preparation and uses of CS nanofibers, a novel work in the domain of the controlled drug delivery by nanofiber-based scaffolds is presented.     

The role of electrospinning in the emerging field of nanomedicine

The fact that in vivo the extracellular matrix (ECM) or substratum with which cells interact often includes topography at the nanoscale underscores the importance of investigating cell-substrate interactions and performing cell culture at the submicron scale. An important and exciting direction of research in nanomedicine would be to gain an understanding and exploit the cellular response to nanostructures. Electrospinning is a simple and versatile technique that can produce a macroporous scaffold comprising randomly oriented or aligned nanofibers. It can also accommodate the incorporation of drug delivery function into the fibrous scaffold. Endowed with both topographical and biochemical signals such electrospun nanofibrous scaffolds may provide an optimal microenvironment for the seeded cells. This review covers the analysis and control of the electrospinning process, and describes the types of electrospun fibers fabricated for biomedical applications such as drug delivery and tissue engineering.     

Functional electrospun nanofibrous scaffolds for biomedical applications

Functional nanofibrous scaffolds produced by electrospinning have great potential in many biomedical applications, such as tissue engineering, wound dressing, enzyme immobilization and drug (gene) delivery. For a specific successful application, the chemical, physical and biological properties of electrospun scaffolds should be adjusted to match the environment by using a combination of multi-component compositions and fabrication techniques where electrospinning has often become a pivotal tool. The property of the nanofibrous scaffold can be further improved with innovative development in electrospinning processes, such as two-component electrospinning and in-situ mixing electrospinning. Post modifications of electrospun membranes also provide effective means to render the electrospun scaffolds with controlled anisotropy and porosity. In this article, we review the materials, techniques and post modification methods to functionalize electrospun nanofibrous scaffolds suitable for biomedical applications.     

Drug delivery from gelatin-based systems

Introduction: Carriers for controlled drug release offer many advantages compared with conventional dosage forms. Gelatin has been investigated extensively as a drug delivery carrier, due to its properties and history of safe use in a wide range of medical applications.

Areas covered: Gelatin was shown to be versatile due to its intrinsic features that enable the design of different carrier systems, such as microparticles and nanoparticles, fibers and even hydrogels. Gelatin microparticles can serve as vehicles for cell amplification and for delivery of large bioactive molecules, whereas gelatin nanoparticles are better suited for intravenous delivery or for drug delivery to the brain. Gelatin fibers contain a high surface area-to-volume ratio, whereas gelatin hydrogels can trap molecules between the polymer’s crosslink gaps, allowing these molecules to diffuse into the blood stream. Another interesting area is the combination of tissue bioadhesive-based gelatin with controlled drug release for pain management and wound healing.

Expert opinion: The modification of gelatin and its combinations with other biomaterials have demonstrated the flexibility of these systems and can be employed for meeting the challenges of finding ideal carrier systems that enable specific, targeted and controlled release in response to demands in the body.     

Delivering bioactive molecules as instructive cues to engineered tissues

Introduction : Growth factors and other bioactive molecules play a crucial role in the creation of functional engineered tissues from dissociated cells.

Areas covered : This review discusses the delivery of bioactive molecules – particularly growth factors – to affect cellular function in the context of tissue engineering. We discuss the primary biological themes that are addressed by delivering bioactives, the types of molecules that are to be delivered, the major materials used in producing scaffolds and/or drug delivery systems, and the principal drug delivery strategies.

Expert opinion : Drug delivery systems have allowed the sustained release of bioactive molecules to engineered tissues, with marked effects on tissue function. Sophisticated drug delivery techniques will allow precise recapitulation of developmental milestones by providing temporally distinct patterns of release of multiple bioactives. High-resolution patterning techniques will allow tissue constructs to be designed with precisely defined areas where bioactives can act. New biological discoveries, just as the development of small molecules with potent effects on cell differentiation, will likely have a marked impact on the field.     

Injectable matrices and scaffolds for drug delivery in tissue engineering

Injectable matrices and depots have been the subject of much research in the field of drug delivery. The classical tissue engineering paradigm includes a matrix or scaffold to facilitate tissue growth and provide structural support, cells, and the delivery of bioactive molecules. As both tissue engineering and drug delivery techniques benefit from the use of injectable materials due to the minimal invasiveness of an injection, significant crossover should be observed between injectable materials in both fields. This review aims to outline injectable materials and processing techniques used in both tissue engineering and drug delivery and to describe methods by which current injectable materials in the field of drug delivery can be adapted for use as injectable scaffolds for tissue engineering.     

Dexamethasone loaded multi-layer poly-l-lactic acid/pluronic P123 composite electrospun nanofiber scaffolds for bone tissue engineering and drug delivery

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA–P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA–P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.     

Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future.     

An overview of nanofiber-based antibacterial drug design

Introduction: Conventional administration of antibacterial drugs to the human body can cause vital problems such as dose dependent systemic toxicity and bacterial resistance which prevent the healing process. In this regard, recent studies have been devoted to producing nanofiber based antibacterial drug delivery approaches which surpass bacterial resistance and toxicological issues.

Areas covered: This review summarizes latest developments in the production of antibacterial nanofibers, nanofiber based antibacterial action mechanisms and release profiles of nanofibers. In the first section, key challenges of antibacterial nanofibers and release and non-release antibacterial action mechanisms of nanofibers are highlighted. In the second section, routes of antibacterial nanofiber design have been given. Factors affecting drug release mechanisms have been discussed elaborately in the final section. Literature was surveyed from research articles, standard sources (WOS and Scopus) and clinical trials.

Expert opinion: New generation nanofibers provide high drug loading capacity and efficiency with their high surface area and tunable pore size. They also enable sustained and controlled release of antibacterial drugs with basic (direct incorporation, physically adsorption or chemically surface modification of antibacterial drugs), advanced (core–shell structure, nanoparticle decorated and multidrug loaded) and smart (stimuli responsive) antibacterial nanofiber design strategies.     

Small molecule delivery through nanofibrous scaffolds for musculoskeletal regenerative engineering

Musculoskeletal regenerative engineering approach using small bioactive molecules in conjunction with advanced materials has emerged as a highly promising strategy for musculoskeletal repair and regeneration. Advanced biomaterials technologies have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as vehicles for the controlled delivery of small molecule drugs. This review article highlights recent advances in nanofiber-based delivery of small molecules for musculoskeletal regenerative engineering. The article concludes with perspectives on the challenges and future directions.From the Clinical EditorIn this review, advances in nanofiber-based delivery of small molecules are discussed from the standpoint of their potential role in musculoskeletal regenerative engineering, highlighting both future directions and current challenges.     

Chitosan-Based Particles as Controlled Drug Delivery Systems

Chitosan, a natural-based polymer obtained by alkaline deacetylation of chitin, is nontoxic, biocompatible, and biodegradable. These properties make chitosan a good candidate for conventional and novel drug delivery systems. This article reviews the approaches aimed to associate bioactive molecules to chitosan in the form of colloidal structures and analyzes the evidence of their efficacy in improving the transport of the associated molecule through mucosae and epithelia. Chitosan forms colloidal particles and entraps bioactive molecules through a number of mechanisms, including chemical crosslinking, ionic crosslinking, and ionic complexation. A possible alternative of chitosan by the chemical modification also has been useful for the association of bioactive molecules to polymer and controlling the drug release profile. Because of the high affinity of chitosan for cell membranes, it has been used as a coating agent for liposome formulations. This review also examines the advances in the application of chitosan and its derivatives to nonviral gene delivery and gives an overview of transfection studies that use chitosan as a transfection agent. From the studies reviewed, we concluded that chitosan and its derivatives are promising materials for controlled drug and nonviral gene delivery.     

Chitosan-based particles as controlled drug delivery systems

Chitosan, a natural-based polymer obtained by alkaline deacetylation of chitin, is nontoxic, biocompatible, and biodegradable. These properties make chitosan a good candidate for conventional and novel drug delivery systems. This article reviews the approaches aimed to associate bioactive molecules to chitosan in the form of colloidal structures and analyzes the evidence of their efficacy in improving the transport of the associated molecule through mucosae and epithelia. Chitosan forms colloidal particles and entraps bioactive molecules through a number of mechanisms, including chemical crosslinking, ionic crosslinking, and ionic complexation. A possible alternative of chitosan by the chemical modification also has been useful for the association of bioactive molecules to polymer and controlling the drug release profile. Because of the high affinity of chitosan for cell membranes, it has been used as a coating agent for liposome formulations. This review also examines the advances in the application of chitosan and its derivatives to nonviral gene delivery and gives an overview of transfection studies that use chitosan as a transfection agent. From the studies reviewed, we concluded that chitosan and its derivatives are promising materials for controlled drug and nonviral gene delivery.     

Bioactive Electrospun Scaffolds Delivering Growth Factors and Genes for Tissue Engineering Applications

A biomaterial scaffold is one of the key factors for successful tissue engineering. In recent years, an increasing tendency has been observed toward the combination of scaffolds and biomolecules, e.g. growth factors and therapeutic genes, to achieve bioactive scaffolds, which not only provide physical support but also express biological signals to modulate tissue regeneration. Huge efforts have been made on the exploration of strategies to prepare bioactive scaffolds. Within the past five years, electrospun scaffolds have gained an exponentially increasing popularity in this area because of their ultrathin fiber diameter and large surface-volume ratio, which is favored for biomolecule delivery. This paper reviews current techniques that can be used to prepare bioactive electrospun scaffolds, including physical adsorption, blend electrospinning, coaxial electrospinning, and covalent immobilization. In addition, this paper also analyzes the existing challenges (i.e., protein instability, low gene transfection efficiency, and difficulties in accurate kinetics prediction) to achieve biomolecule release from electrospun scaffolds, which necessitate further research to fully exploit the biomedical applications of these bioactive scaffolds.     

Electrohydrodynamics: A facile technique to fabricate drug delivery systems

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material's functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drug delivery devices.     

Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

Chitosan, a natural cationic polysaccharide, is prepared industrially by the hydrolysis of the aminoacetyl groups of chitin, a naturally available marine polymer. Chitosan is a non-toxic, biocompatible and biodegradable polymer and has attracted considerable interest in a wide range of biomedical and pharmaceutical applications including drug delivery, cosmetics, and tissue engineering. The primary hydroxyl and amine groups located on the backbone of chitosan are responsible for the reactivity of the polymer and also act as sites for chemical modification. However, chitosan has certain limitations for use in controlled drug delivery and tissue engineering. These limitations can be overcome by chemical modification. Thus, modified chitosan hydrogels have gained importance in current research on drug delivery and tissue engineering systems. This paper reviews the general properties of chitosan, various methods of modification, and applications of modified chitosan hydrogels.     

A Three-Dimensional Polycaprolactone Scaffold Combined with a Drug Delivery System Consisting of Electrospun Nanofibers

A new three-dimensional (3D) scaffold containing a functional drug delivery system (DDS) consisting of electrospun micro/nanofibers is proposed. In the DDS scaffold, a core-shell laminated, structured, electrospun mat of hydrophobic polycaprolactone (PCL) and hydrophilic poly(ethylene oxide) (PEO)/rhodamine-B fibers was embedded in the normal 3D PCL scaffold, which was fabricated by a melt-plotting system. Rhodamine release from the scaffold was controlled physically by the thickness change of the PCL layer, and initial burst in drug release was eliminated by an appropriate thickness of the PCL layer. This simple technique may be useful in fabricating DDS-functional scaffolds for the clinical areas not only of bone and skin regeneration, but also of other tissue regeneration areas, regardless of the degradation rate of the structural scaffold.     

Engineering biodegradable polyester particles with specific drug targeting and drug release properties

Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres and nanoparticles remain the focus of intensive research effort directed to the controlled release and in vivo localization of drugs. In recent years engineering approaches have been devised to create novel micro- and nano-particles which provide greater control over the drug release profile and present opportunities for drug targeting at the tissue and cellular levels. This has been possible with better understanding and manipulation of the fabrication and degradation processes, particularly emulsion-solvent extraction, and conjugation of polyesters with ligands or other polymers before or after particle formation. As a result, particle surface and internal porosity have been designed to meet criteria-facilitating passive targeting (e.g., for pulmonary delivery), modification of the drug release profile (e.g., attenuation of the burst release) and active targeting via ligand binding to specific cell receptors. It is now possible to envisage adventurous applications for polyester microparticles beyond their inherent role as biodegradable, controlled drug delivery vehicles. These may include drug delivery vehicles for the treatment of cerebral disease and tumor targeting, and co-delivery of drugs in a pulsatile and/or time-delayed fashion.     

Biomaterial-based scaffolds – current status and future directions

Introduction: Biomaterial-based scaffold formulations (three-dimensional Porous matrix, nano-fibre mesh, hydrogels and microspheres) are the major components that are used to deliver the bioactive molecules into the body organs through different routes for an effective treatment of various diseases.

Areas covered: Various fabrication techniques such as freeze-drying, polymerisation, spray drying, gas foaming, supercritical fluid technology, etc., are successfully used for fabrication of scaffold formulations. Due to their unique characteristics, these formulations are widely used against various diseases such as tuberculosis, bone defects, cartilage repair, skin diseases, cardiovascular diseases, periodontal diseases, wound dressing, etc.

Expert opinion: The study of biomaterial-based scaffold formulations is exhilarating with novel approaches to drug/cell/gene delivery being developed all the time. At present, there is a huge extent of research being performed worldwide on all aspects of tissue engineering/drug or gene delivery. In the future, the main focus will be on the development of more patient compliant, sustained and controlled delivery systems against various diseases by modification of polymers, manufacturing technologies as well as carrier systems.