Hydrophilic and hydrophobic drug release from core (polyvinylpyrrolidone)-sheath (ethyl cellulose) pressure-spun fibers.

A core-sheath structure is one of the methods developed to overcome the challenges often faced when using monolithic fibers for drug delivery. In this study, fibers based on polyvinylpyrrolidone (core) and ethyl cellulose (sheath) were successfully produced using a novel core-sheath pressure-spinning process. For comparison, these two polymers were also processed into as blend fibers. All samples were then investigated for their performances in releasing water-soluble ampicillin (AMP) and poorly water-soluble ibuprofen (IBU) model drugs. Scanning electron,digital and confocal microscopy confirmed that fibers with a core-sheath structure were successfully made. Fourier transform infrared spectroscopy showed the success of the pressure-spinning technique in encapsulating AMP/IBU in all fiber samples. Compared to blend fibers, the core-sheath fibers had better performance in encapsulating both water-soluble and poorly water-soluble drugs. Moreover, the core-sheath structure was able to reduce the initial burst release and provided a better sustained release profile than the blend fiber analog. In conclusion, the pressure-spinning method was capable of producing core-sheath and blend fibers that could be used for the loading of either hydrophilic or hydrophobic drugs for controlled drug delivery systems.

Nanofiber Based on Electrically Conductive Materials for Biosensor Applications.

Biosensors are analytical tools that enable the transmission of different signals produced from the target analyte to a transducer for the production of real-time clinical diagnostic devices by obtaining meaningful results. Recent research demonstrates that the production of structured nanofiber through various methods has come to light as a potential platform for enhancing the functionality of biosensing devices. The general trend is towards the use of nanofibers for electrochemical biosensors. However, optical and mechanical biosensors are being developed by functionalization of nanofibers. Such nanofibers exhibit a high surface area to volume ratio, surface porosity, electroconductivity and variable morphology. In addition, nanosized structures have shown to be effective as membranes for immobilizing bioanalytes, offering physiologically active molecules a favorable microenvironment that improves the efficiency of biosensing. Cost effective, wearable biosensors are crucial for point of care diagnostics. This review aims to examine the electrically conductive materials, potential forming methods, and wide-ranging applications of nanofiber-based biosensing platforms, with an emphasis on transducers incorporating mechanical, electrochemical and optical and bioreceptors involving cancer biomarker, urea, DNA, microorganisms, primarily in the last decade. The appealing properties of nanofibers mats and the attributes of the biorecognition components are also stated and explored. Finally, consideration is given to the difficulties now affecting the design of nanofiber-based biosensing platforms as well as their future potential.

Facile One-Step Synthesis of PVDF Bead-on-String Fibers by Pressurized Gyration for Reusable Face Masks.

Single-use face masks pose a threat to the environment and are not cost-effective, which prompts the need for developing reusable masks. In this study, pressurized gyration (PG) successfully produced bead-on-string polyvinylidene fluoride (PVDF) fibers with fiber diameters ranging from 2.3 µm to 26.1 µm, and bead diameters ranging from 60.9 µm to 88.5 µm by changing the solution parameters. The effect of the solution parameters on the crystalline phase was studied by Fourier-transform infrared spectroscopy (FT-IR), where the ß-phase contents of PG PVDF fibers reached over 75%. The fiber morphology and ß-phase contents of PG PVDF fibers indicated the potential mechanical and electrostatic filtration efficiency of PG PVDF fibers, respectively. Additionally, the hydrophobicity was investigated by static water contact angle tests, and the PVDF fibers showed superior hydrophobicity properties (all samples above 125°) over commercial polypropylene (PP) single-use masks (approximately 107°). This study supports the notion that the PG PVDF fiber mats are a promising candidate for future reusable face masks.

Antimicrobial Fibrous Bandage-like Scaffolds Using Clove Bud Oil.

Wounds are characterised by an anatomical disruption of the skin; this leaves the body exposed to opportunistic pathogens which contribute to infections. Current wound healing bandages do little to protect against this and when they do, they can often utilise harmful additions. Historically, plant-based constituents have been extensively used for wound treatment and are proven beneficial in such environments. In this work, the essential oil of clove bud (Syzygium aromaticum) was incorporated in a polycaprolactone (PCL) solution, and 44.4% (v/v) oil-containing fibres were produced through pressurised gyration. The antimicrobial activity of these bandage-like fibres was analysed using in vitro disk diffusion and the physical fibre properties were also assessed. The work showed that advantageous fibre morphologies were achieved with diameters of 10.90 ± 4.99 µm. The clove bud oil fibres demonstrated good antimicrobial properties. They exhibited inhibition zone diameters of 30, 18, 11, and 20 mm against microbial colonies of C. albicans, E. coli, S. aureus, and S. pyogenes, respectively. These microbial species are commonly problematic in environments where the skin barrier is compromised. The outcomes of this study are thus very promising and suggest that clove bud oil is highly suitable to be applied as a natural sustainable alternative to modern medicine.

Facile One-Pot Method for All Aqueous Green Formation of Biocompatible Silk Fibroin-Poly(Ethylene Oxide) Fibers for Use in Tissue Engineering.

Silk fibroin (SF) fibers are highly regarded in tissue engineering because of their outstanding biocompatibility and tunable properties. A challenge remains in overcoming the trade-off between functioning and biocompatible fibers and the use of cytotoxic, environmentally harmful organic solvents in their processing and formation. The aim of this research was to produce biocompatible SF fibers without the use of cytotoxic solvents, via pressurized gyration (PG). Aqueous SF was blended with poly(ethylene oxide) (PEO) in ratios of 80:20 (labeled SF-PEO 80:20) and 90:10 (labeled SF-PEO 90:10) and spun into fibers using PG, assisted by a range of applied pressures and heat. Pure PEO (labeled PEO-Aq) and SF solubilized in hexafluoro-isopropanol (HFIP) (labeled SF-HFIP) and aqueous SF (labeled SF-Aq) were also prepared for comparison. The resulting fibers were characterized using SEM, TGA, and FTIR. Their in vitro cell behavior was analyzed using a Live/Dead assay and cell proliferation studies with the SaOS-2 human bone osteosarcoma cell line (ATCC, HTB-85) and human fetal osteoblast cells (hFob) (ATCC, CRL-11372) in 2D culture conditions. Fibers in the micrometer range were successfully produced using SF-PEO blends, SF-HFIP, and PEO-Aq. The fiber thickness ranged from 0.71 ± 0.17 µm for fibers produced using SF-PEO 90:10 with no applied pressure to 2.10 ± 0.78 µm for fibers produced using SF-PEO 80:10 with 0.3 MPa applied pressure. FTIR confirmed the presence of SF via amide I and amide II bands in the blend fibers because of a change in structural conformation. No difference was observed in thermogravimetric properties among varying pressures and no significant difference in fiber diameters for pressures. SaOS-2 cells and hFOb cell studies demonstrated higher cell densities and greater live cells on SF-PEO blends when compared to SF-HFIP. This research demonstrates a scalable and green method of producing SF-based constructs for use in bone-tissue engineering applications.

Co-Axial Gyro-Spinning of PCL/PVA/HA Core-Sheath Fibrous Scaffolds for Bone Tissue Engineering.

The present study aspires towards fabricating core-sheath fibrous scaffolds by state-of-the-art pressurized gyration for bone tissue engineering applications. The core-sheath fibers comprising dual-phase poly-ε-caprolactone (PCL) core and polyvinyl alcohol (PVA) sheath are fabricated using a novel "co-axial" pressurized gyration method. Hydroxyapatite (HA) nanocrystals are embedded in the sheath of the fabricated scaffolds to improve the performance for application as a bone tissue regeneration material. The diameter of the fabricated fiber is 3.97 ± 1.31 µm for PCL-PVA/3%HA while pure PCL-PVA with no HA loading gives 3.03 ± 0.45 µm. Bead-free fiber morphology is ascertained for all sample groups. The chemistry, water contact angle and swelling behavior measurements of the fabricated core-sheath fibrous scaffolds indicate the suitability of the structures in cellular activities. Saos-2 bone osteosarcoma cells are employed to determine the biocompatibility of the scaffolds, wherein none of the scaffolds possess any cytotoxicity effect, while cell proliferation of 94% is obtained for PCL-PVA/5%HA fibers. The alkaline phosphatase activity results suggest the osteogenic activities on the scaffolds begin earlier than day 7. Overall, adaptations of co-axial pressurized gyration provides the flexibility to embed or encapsulate bioactive substances in core-sheath fiber assemblies and is a promising strategy for bone healing.

Harnessing Polyhydroxyalkanoates and Pressurized Gyration for Hard and Soft Tissue Engineering.

Organ dysfunction is a major cause of morbidity and mortality. Transplantation is typically the only definitive cure, challenged by the lack of sufficient donor organs. Tissue engineering encompasses the development of biomaterial scaffolds to support cell attachment, proliferation, and differentiation, leading to tissue regeneration. For efficient clinical translation, the forming technology utilized must be suitable for mass production. Herein, uniaxial polyhydroxyalkanoate scaffolds manufactured by pressurized gyration, a hybrid scalable spinning technique, are successfully used in bone, nerve, and cardiovascular applications. Chorioallantoic membrane and in vivo studies provided evidence of vascularization, collagen deposition, and cellular invasion for bone tissue engineering. Highly efficient axonal outgrowth was observed in dorsal root ganglion-based 3D ex vivo models. Human induced pluripotent stem cell derived cardiomyocytes exhibited a mature cardiomyocyte phenotype with optimal calcium handling. This study confirms that engineered polyhydroxyalkanoate-based gyrospun fibers provide an exciting and unique toolbox for the development of scalable scaffolds for both hard and soft tissue regeneration.

Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection.

A significant proportion of urinary tract infection (UTI) patients experience recurrent episodes, due to deep tissue infection and treatment-resistant bacterial reservoirs. Direct bladder instillation of antibiotics has proved disappointing in treating UTI, likely due to the failure of infused antibiotics to penetrate the bladder epithelium and accumulate to high enough levels to kill intracellular bacteria. This work investigates the use of nitrofurantoin loaded poly(lactic-co-glycolic acid) (PLGA) particles to improve delivery to intracellular targets for the treatment of chronic UTI. Using electrohydrodynamic atomisation, we produced particles with an average diameter of 2.8 µm. In broth culture experiments, the biodegradable particles were effective against a number of UTI-relevant bacterial strains. Dye-loaded particles demonstrated that intracellular delivery was achieved in all cells in 2D cultures of a human bladder epithelial progenitor cell line in a dose-dependent manner, achieving far higher efficiency and concentration than equivalent quantities of free drug. Time-lapse video microscopy confirmed that delivery occurred within 30 min of administration, to 100% of cells. Moreover, the particles were able to deliver the drug to cells through multiple layers of a 3D human bladder organoid model causing minimal cell toxicity, displaying superior killing of bacterial reservoirs harboured within bladder cells compared with unencapsulated drug. The particles were also able to kill bacterial biofilms more effectively than the free drug. These results illustrate the potential for using antibiotic-loaded microparticles to effectively treat chronic UTIs. Such a delivery method could be extrapolated to other clinical indications where robust intracellular delivery is required, such as oncology and gene therapy.

Effectiveness of Oil-Layered Albumin Microbubbles Produced Using Microfluidic T-Junctions in Series for In Vitro Inhibition of Tumor Cells.

This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in the drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of a gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to the control.

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches.

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

Copolymer Composition and Nanoparticle Configuration Enhance in vitro Drug Release Behavior of Poorly Water-soluble Progesterone for Oral Formulations.

HYPOTHESIS: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. EXPERIMENTS: Six formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. FINDINGS: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1±54.8 to 588.0±92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9±1.4% and 70.7±3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0±1.7% and 57.5±2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro.

Videographic Analysis of Blink Dynamics following Upper Eyelid Blepharoplasty and Its Association with Dry Eye.

This study was undertaken to characterize the effects of upper eyelid blepharoplasty on blink dynamics and to evaluate the hypothesis that changes in blink dynamics following blepharoplasty are associated with postoperative dry eye. METHODS: The voluntary blink of 14 eyes of 7 patients with dermatochalasis undergoing upper eyelid blepharoplasty was recorded with a high-speed camera preoperatively and 6-8 months postoperatively, alongside a group of 11 controls. The images were analyzed for palpebral aperture, blink duration, and maximum velocity during opening and closing phases. Patients undergoing blepharoplasty were assessed for dry eye symptoms pre- and postoperatively at 6-8 months using the ocular surface disease index score. RESULTS: Despite intraoperative orbicularis oculi resection, there was no significant compromise of blink duration or maximum velocity of eyelid opening or closure post-blepharoplasty. Postoperatively, patients had an increase in palpebral aperture compared with both preoperatively (8.71 versus 7.85 mm; P = 0.013) and control groups (8.71 versus 7.87 mm; P = 0.04). Postoperatively at 6-8 months, there was an increase in dry eye symptoms in 6 of 7 patients compared with preoperatively (ocular surface disease index, 16.6 versus 12.5; P < 0.05). There was no positive correlation between the increase in palpebral aperture and the increase in dry eye symptoms (r = -0.4; P = 0.30). CONCLUSIONS: Using modern videographic technology, this study demonstrates that upper eyelid blepharoplasty results in an increase in resting palpebral aperture but has no effect on dynamic blink parameters. Changes in palpebral aperture or blink dynamics are unlikely to be the cause of dry eye syndrome following blepharoplasty.

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells.

Mucoadhesion of Progesterone-Loaded Drug Delivery Nanofiber Constructs.

Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant ( p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion.

The development of progesterone-loaded nanofibers using pressurized gyration: A novel approach to vaginal delivery for the prevention of pre-term birth.

Recent evidence has continued to support the applicability of progesterone in preventing preterm birth, hence the development of an appropriate vaginal delivery system for this drug would be of considerable interest. Here, we describe the development of progesterone-loaded bioadhesive nanofibers using pressurized gyration for potential incorporation into a vaginal insert, with a particular view to addressing the challenges of incorporating a poorly water-soluble drug into a hydrophilic nanofiber carrier. Polyethylene oxide and carboxymethyl cellulose were chosen as polymers to develop the carrier systems, based on previous evidence of their yielding mucoadhesive nanofibers using the pressurized gyration technique. The fabrication parameters such as solvent system, initial drug loading and polymer composition were varied to facilitate optimisation of fiber structure and efficiency of drug incorporation. Such studies resulted in the formation of nanofibers with satisfactory surface appearance, diameters in the region of 400 nm and loading of up to 25% progesterone. Thermal and spectroscopic analyses indicated that the drug was incorporated in a nanocrystalline state. Release from the drug-loaded fibers indicated comparable rates of progesterone dissolution to that of Cyclogest, a commercially available progesterone pessary, allowing release over a period of hours. Overall, the study has shown that pressurized gyration may produce bioadhesive progesterone-loaded nanofibers which have satisfactory loading of a poorly water-soluble drug as well as having suitable structural and release properties. The technique is also capable of producing fibers at a yield commensurate with practical applicability, hence we believe that the approach shows considerable promise for the development of progesterone dosage forms for vaginal application.

Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering.

Cardiac tissue engineering (CTE) is currently a prime focus of research because of an enormous clinical need. In the present work, a novel functional material, poly(3-hydroxyoctanoate), P(3HO), a medium chain-length polyhydroxyalkanoate (PHA), produced using bacterial fermentation, was studied as a new potential material for CTE. Engineered constructs with improved mechanical properties, crucial for supporting the organ during new tissue regeneration, and enhanced surface topography, to allow efficient cell adhesion and proliferation, were fabricated. Results showed that the mechanical properties of the final patches were close to that of cardiac muscle. Biocompatibility of neat P(3HO) patches, assessed using neonatal ventricular rat myocytes (NVRM), showed that the polymer was as good as collagen in terms of cell viability, proliferation and adhesion. Enhanced cell adhesion and proliferation properties were observed when porous and fibrous structures were incorporated into the patches. In addition, no deleterious effect was observed on adult cardiomyocyte contraction when cardiomyocytes were seeded on the P(3HO) patches. Hence, P(3HO)-based multifunctional cardiac patches are promising constructs for efficient CTE. This work will have a positive impact on the development of P(3HO) and other PHAs as a novel new family of biodegradable functional materials with huge potential in a range of different biomedical applications, particularly CTE, leading to further interest and exploitation of these materials. Copyright © 2016 John Wiley & Sons, Ltd.

Drug Delivery Strategies for Platinum-Based Chemotherapy.

Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum-based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multidrug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release. The aim of this review is to look at these strategies and recent scientific and clinical developments.

Electrohydrodynamic fabrication of core-shell PLGA nanoparticles with controlled release of cisplatin for enhanced cancer treatment.

Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core-shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial "burst" and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 µM) compared to free drug (EC50 =9 µM) and uniform CDDP-distributed NPs (EC50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment.