Electrospun drug-loaded scaffolds for nervous system repair.

Nervous system injuries, encompassing peripheral nerve injury (PNI), spinal cord injury (SCI), and traumatic brain injury (TBI), present significant challenges to patients' wellbeing. Traditional treatment approaches have limitations in addressing the complexity of neural tissue regeneration and require innovative solutions. Among emerging strategies, implantable materials, particularly electrospun drug-loaded scaffolds, have gained attention for their potential to simultaneously provide structural support and controlled release of therapeutic agents. This review provides a thorough exploration of recent developments in the design and application of electrospun drug-loaded scaffolds for nervous system repair. The electrospinning process offers precise control over scaffold characteristics, including mechanical properties, biocompatibility, and topography, crucial for creating a conducive environment for neural tissue regeneration. The large surface area of the resulting fibrous networks enhances biomolecule attachment, influencing cellular behaviors such as adhesion, proliferation, and migration. Polymeric electrospun materials demonstrate versatility in accommodating a spectrum of therapeutics, from small molecules to proteins. This enables tailored interventions to accelerate neuroregeneration and mitigate inflammation at the injury site. A critical aspect of this review is the examination of the interplay between structural properties and pharmacological effects, emphasizing the importance of optimizing both aspects for enhanced therapeutic outcomes. Drawing upon the latest advancements in the field, we discuss the promising outcomes of preclinical studies using electrospun drug-loaded scaffolds for nervous system repair, as well as future perspectives and considerations for their design and implementation. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Advanced Formulation Approaches for Proteins.

Proteins and peptides are highly desirable as therapeutic agents, being highly potent and specific. However, there are myriad challenges with processing them into patient-friendly formulations: they are often unstable and have a tendency to aggregate or degrade upon storage. As a result, the vast majority of protein actives are delivered parenterally as solutions, which has a number of disadvantages in terms of cost, accessibility, and patient experience. Much work has been undertaken to develop new delivery systems for biologics, but to date this has led to relatively few products on the market. In this chapter, we review the challenges faced when developing biologic formulations, discuss the technologies that have been explored to try to overcome these, and consider the different delivery routes that can be applied. We further present an overview of the currently marketed products and assess the likely direction of travel in the next decade.

Development of ibuprofen-loaded electrospun materials suitable for surgical implantation in peripheral nerve injury.

The development of nerve wraps for use in the repair of peripheral nerves has shown promise over recent years. A pharmacological effect to improve regeneration may be achieved by loading such materials with therapeutic agents, for example ibuprofen, a non-steroidal anti-inflammatory drug with neuroregenerative properties. In this study, four commercially available polymers (polylactic acid (PLA), polycaprolactone (PCL) and two co-polymers containing different ratios of PLA to PCL) were used to fabricate ibuprofen-loaded nerve wraps using blend electrospinning. In vitro surgical handling experiments identified a formulation containing a PLA/PCL 70/30 molar ratio co-polymer as the most suitable for in vivo implantation. In a rat model, ibuprofen released from electrospun materials significantly improved the rate of axonal growth and sensory recovery over a 21-day recovery period following a sciatic nerve crush. Furthermore, RT-qPCR analysis of nerve segments revealed that the anti-inflammatory and neurotrophic effects of ibuprofen may still be observed 21 days after implantation. This suggests that the formulation developed in this work could have potential to improve nerve regeneration in vivo.

The blending effect of natural polysaccharides with nano-zirconia towards the removal of fluoride and arsenate from water.

Nano-zirconia (ZO) was synthesized using a microwave-assisted one-pot precipitation route. Two biopolymers, chitosan (CTS) and carboxymethyl cellulose were blended with ZO at different w/w ratios. The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here.

Nanomagnetite- and Nanotitania-Incorporated Polyacrylonitrile Nanofibers for Simultaneous Cd(II)- and As(V)-Ion Removal Applications.

This work reports the fabrication of nanomagnetite- and nanotitania-incorporated polyacrylonitrile nanofibers (MTPANs) by an electrospinning process, which has the potential to be used as a membrane material for the selective removal of Cd(II) and As(V) in water. The fiber morphology was characterized by scanning electron microscopy (SEM). The incorporation of nanomagnetite and nanotitania in the composite fiber matrix was confirmed by energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. The fibers doped with nanomagnetite and nanotitania (MPAN and TPAN fibers, respectively), as well as MTPAN and neat polycrylonitrile (PAN) fibers, after thermally stabilizing at 275 °C in air, were assessed for their comparative As(V)- and Cd(II)-ion removal capacities. The isotherm studies indicated that the highest adsorption of Cd(II) was shown by MTPAN, following the Langmuir model with a q m of 51.5 mg/m2. On the other hand, MPAN showed the highest As(V)adsorption capacity, following the Freundlich model with a K F of 0.49. The mechanism of adsorption of both Cd(II) and As(V) by fibers was found to be electrostatically driven, which was confirmed by correlating the point of zero charges (PZC) exhibited by fibers with the pH of maximum ion adsorptions. The As(V) adsorption on MPAN occurs by an inner-sphere mechanism, whereas Cd(II) adsorption on MTPAN is via both surface complexation and an As(V)-assisted inner-sphere mechanism. Even though the presence of coexistent cations, Ca(II) and Mg(II), has been shown to affect the Cd(II) removal by MTPAN, the MTPAN structure shows >50% removal efficiency even for minute concentrations (0.5 ppm) of Cd(II) in the presence of high common ion concentrations (10 ppm). Therefore, the novel polyacrylonitrile-based nanofiber material has the potential to be used in polymeric filter materials used in water purification to remove As(V) and Cd(II) simultaneously.

Encapsulation of Pharmaceutical and Nutraceutical Active Ingredients Using Electrospinning Processes.

Electrospinning is an inexpensive and powerful method that employs a polymer solution and strong electric field to produce nanofibers. These can be applied in diverse biological and medical applications. Due to their large surface area, controllable surface functionalization and properties, and typically high biocompatibility electrospun nanofibers are recognized as promising materials for the manufacturing of drug delivery systems. Electrospinning offers the potential to formulate poorly soluble drugs as amorphous solid dispersions to improve solubility, bioavailability and targeting of drug release. It is also a successful strategy for the encapsulation of nutraceuticals. This review aims to briefly discuss the concept of electrospinning and recent progress in manufacturing electrospun drug delivery systems. It will further consider in detail the encapsulation of nutraceuticals, particularly probiotics.

Structure-Activity Relationship of Lanthanide-Incorporated Nano-Hydroxyapatite for the Adsorption of Fluoride and Lead.

The growing demand for water purification provided the initial momentum to produce lanthanide-incorporated nano-hydroxyapatite (HAP) such as HAP·CeO2, HAP·CeO2·La(OH)3 (2:1), and HAP·CeO2·La(OH)3 (3:2). These materials open avenues to remove fluoride and lead ions from contaminated water bodies effectively. Composites of HAP containing CeO2 and La(OH)3 were prepared using in situ wet precipitation of HAP, followed by the addition of Ce(SO4)2 and La(NO3)3 into the same reaction mixture. The resultant solids were tested for the removal of fluoride and lead ions from contaminated water. It was found that the composite HAP·CeO2 shows fluoride and lead ion removal capacities of 185 and 416 mg/g, respectively. The fluoride removal capacity of the composite was improved when La(OH)3 was incorporated and it was observed that the composite HAP·CeO2·La(OH)3 (3:2) has the highest recorded fluoride removal capacity of 625 mg/g. The materials were characterized using scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) spectrometry, Fourier transform infrared (FT-IR) spectrometry, X-ray powder diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) surface area analysis. Analysis of results showed that Ce and La are incorporated in the HAP matrix. Results of kinetic and leaching analyses indicated a chemisorptive behavior during fluoride and lead ion adsorption by the composites; meanwhile, the thermodynamic profile shows a high degree of feasibility for fluoride and lead adsorption.

Biopolymer-Based Nanohydroxyapatite Composites for the Removal of Fluoride, Lead, Cadmium, and Arsenic from Water.

In this study, hydroxyapatite (HAP) nanocomposites were prepared with chitosan (HAP-CTS), carboxymethyl cellulose (HAP-CMC), alginate (HAP-ALG), and gelatin (HAP-GEL) using a simple wet chemical in situ precipitation method. The synthesized materials were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Brunauer-Emmett-Teller surface area analysis, and thermogravimetric analysis. This revealed the successful synthesis of composites with varied morphologies. The adsorption abilities of the materials toward Pb(II), Cd(II), F-, and As(V) were explored, and HAP-CTS was found to have versatile adsorption properties for all of the ions, across a wide range of concentrations and pH values, and in the presence of common ions found in groundwater. Additionally, X-ray photoelectron spectroscopy and energy-dispersive X-ray spectroscopy confirmed the affinity of HAP-CTS toward multi-ion mixture containing all four ions. HAP-CTS was hence engineered into a more user-friendly form, which can be used to form filters through its combination with cotton and granular activated carbon. A gravity filtration study indicates that the powder form of HAP-CTS is the best sorbent, with the highest breakthrough capacity of 3000, 3000, 2600, and 2000 mL/g for Pb(II), Cd(II), As(V), and F-, respectively. Hence, we propose that HAP-CTS could be a versatile sorbent material for use in water purification.

A simple route to functionalising electrospun polymer scaffolds with surface biomolecules.

Surface functionalisation of polymeric electrospun scaffolds with therapeutic biomolecules is often explored in regenerative medicine and tissue engineering. However, the bioconjugation method must be carefully selected to prevent partial or full loss of activity of the biomolecule following chemical manipulation. Perfluorophenyl azide bearing a N-hydroxysuccinimide (PFPA-NHS) active ester group is a versatile tool for UV-initiated covalent coupling of amine-containing molecules to hydrocarbon-based polymers, such as polydioxanone or polycaprolactone (PCL). This study therefore explored the feasibility of PFPA-NHS functionalisation of electrospun PCL scaffolds with model biomolecules. Protein conjugation was extensively explored using fluorescence staining and attachment studies, confirming the retention of amine coupling capability following photografting of PFPA-NHS to the PCL surface. The effect of the washing method used to remove unreacted PFPA was explored in Caco-2 cell viability studies, and it was determined that sonication washing is required to avoid cell death. A model enzyme, catalase, was then successfully attached to the surface of PCL scaffolds for potential applications in oncological photodynamic therapy. Catalase retained its enzymatic activity following attachment to the fibres and the majority of the enzyme (~60%) remained bound to the fibre after incubation in an aqueous environment for six days. The anticipated prolonged presentation and sustained release of proteins as a result of PFPA-NHS conjugation could be advantageous in progressing protein-based therapies.

Electrospinning for healthcare: recent advancements.

Electrospinning is a simple route to generate polymer-based fibres with diameters on the nano- to micron-scale. It has been very widely explored in biomedical science for applications including drug delivery systems, diagnostic imaging, theranostics, and tissue engineering. This extensive literature reveals that a diverse range of functional components including small molecule drugs, biologics, and nanoparticles can be incorporated into electrospun fibres, and it is possible to prepare materials with complex compartmentalised architectures. This perspective article briefly introduces the electrospinning technique before considering its potential applications in biomedicine. Particular attention is paid to the translation of electrospinning to the clinic, including the need to produce materials at large scale and the requirement to do so under Good Manufacturing Practice conditions. We finish with a summary of the key current challenges and future perspectives.

Protein encapsulation by electrospinning and electrospraying.

Given the increasing interest in the use of peptide- and protein-based agents in therapeutic strategies, it is fundamental to develop delivery systems capable of preserving the biological activity of these molecules upon administration, and which can provide tuneable release profiles. Electrohydrodynamic (EHD) techniques, encompassing electrospinning and electrospraying, allow the generation of fibres and particles with high surface area-to-volume ratios, versatile architectures, and highly controllable release profiles. This review is focused on exploring the potential of different EHD methods (including blend, emulsion, and co-/multi-axial electrospinning and electrospraying) for the development of peptide and protein delivery systems. An overview of the principles of each technique is first presented, followed by a survey of the literature on the encapsulation of enzymes, growth factors, antibodies, hormones, and vaccine antigens using EHD approaches. The possibility for localised delivery using stimuli-responsive systems is also explored. Finally, the advantages and challenges with each EHD method are summarised, and the necessary steps for clinical translation and scaled-up production of electrospun and electrosprayed protein delivery systems are discussed.

The Effect of Solvent Vapor Annealing on Drug-Loaded Electrospun Polymer Fibers.

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(ԑ-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.

Co-Processed Excipients for Dispersible Tablets-Part 1: Manufacturability.

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr's index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (< 1% after 15 min), rapid disintegration times (27-49 s) and produced dispersions of ideal fineness (< 250 µm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients.

Co-Processed Excipients for Dispersible Tablets-Part 2: Patient Acceptability.

Palatability and patient acceptability are critical attributes of dispersible tablet formulation. Co-processed excipients could provide improved organoleptic profile due to rational choice of excipients and manufacturing techniques. The aim of this study was to identify the most suitable co-processed excipient to use within directly compressible dispersible tablet formulations. Nine excipients, selected based on successful manufacturability, were investigated in a randomised, preference and acceptability testing in 24 healthy adult volunteers. Excipients were classified in order of preference as follows (from most preferred): SmartEx QD100 > F-Melt Type C > F-Melt Type M > MicroceLac > Ludiflash > CombiLac > Pharmaburst 500 > Avicel HFE-102 > Avicel PH-102. Broad differences were identified in terms of acceptability, with SmartEx QD100 being 'very acceptable', F-Melt Type C, F-Melt Type M and MicroceLac being 'acceptable', Ludiflash, CombiLac and Pharmaburst 500 being 'neutral' and Avicel products being 'very unacceptable' based on ratings using five-point hedonic scales. Organoleptic differences were ascribed to different composition and physical properties of excipients, resulting in dissimilar taste and mouth-feel. Excipients with particle size in water larger than 200-250 µm were considered poorly acceptable, which supports the use of this value as a threshold for maximum particle size of dispersible formulation. The most promising co-processed excipients for directly compressible dispersible tablets were successfully identified.