Recent developments in the use of centrifugal spinning and pressurized gyration for biomedical applications.

Centrifugal spinning is a technology used to generate small diameter fibers and has been extensively studied for its vast applications in biomedical engineering. Centrifugal spinning is known for its rapid production rate and has inspired the creation of other technologies which leverage the high-speed rotation, namely Pressurized Gyration. Pressurized gyration incorporates a unique applied gas pressure which serves to provide additional control over the fiber production process. The resulting fibers are uniquely suitable for a range of healthcare-related applications that are thoroughly discussed in this work, which involve scaffolds for tissue engineering, solid dispersions for drug delivery, antimicrobial meshes for filtration and bandage-like fibrous coverings for wound healing. In this review, the notable recent developments in centrifugal spinning and pressurized gyration are presented and how these technologies are being used to further the range of uses of biomaterials engineering, for example the development of core-sheath fabrication techniques for multi-layered fibers and the combination with electrospinning to produce advanced fiber mats. The enormous potential of these technologies and their future advancements highlights how important they are in the biomedical discipline. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Pressure-Spun Fibrous Surgical Sutures for Localized Antibacterial Delivery: Development, Characterization, and In Vitro Evaluation.

Surgical sutures designed to prevent infection are critical in addressing antibiotic-resistant pathogens that cause surgical site infections. Instead of antibiotics, alternative materials such as biocides have been assessed for coating commercially used sutures due to emerging antibiotic resistance concerns worldwide. This study has a new approach to the development of fibrous surgical sutures with the ability to deliver localized antibacterial agents. A new manufacturing process based on pressure spinning was used for the first time in the production of fibrous surgical sutures by physically blending antibacterial triclosan (Tri) agent with poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene oxide) (PEO) polymers. Fibrous surgical sutures with virgin PLGA, virgin PEO, different ratios of PLGA-PEO, and different ratios of Tri-loaded PLGA-PEO fibrous sutures were produced to mimic the FDA- and NICE-approved PLGA-based sutures available in the market and compared for their characteristics. They were also tested simultaneously with commercially available sutures to compare their in vitro biodegradation, antibacterial, drug release, and cytotoxicity properties. After in vitro antibacterial testing for 24 h, sutures having 285 ± 12 µg/mg Tri loading were selected as a model for further testing as they exhibited antibacterial activity against all tested bacteria strains. The selected model of antibacterial fibrous sutures exhibited an initial burst of Tri release within 24 h, followed by a sustained release for the remaining time until the sutures completely degraded within 21 days. The cell viability assay showed that these surgical sutures had no cytotoxic effect on mammalian cells.

Donepezil-loaded PLGA-b-PEG Nanoparticles Enhance the Learning and Memory Function of Beta-Amyloid Rat Model of Alzheimer's Disease.

Introduction: Our aim is to reduce the side effects and increase the efficiency of donepezil by formulating donepezil-loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) nanoparticles (NPs) directly targeting amyloid beta (Aß) fibrils in the brain and evaluate behavioral changes in this fibril model of AD. Methods: AD model was developed by intracerebroventricular injection of pre-aggregated ß25-35 fibrils. Rats were intravenously administered either solvent, donepezil-loaded NPs (15µg/kg) or free donepezil (1mg/kg) 3 times for a week except for naïve controls. The effect of treatments on anxiety, motor functions, and cognitive functions was tested by elevated plus maze, locomotor activity, novel object recognition, and Morris's water maze tests, respectively. Results: Accumulation of Aß25-35 fibrils in brain sections was confirmed. Anxiety-like behavior was observed in the Aß Alzheimer and free donepezil treatment groups while donepezil-loaded NP treatment showed hypo-anxiety-like behavior. Donepezil-loaded NPs were successful in treatment of short-term memory deficit better than free donepezil injection. In Morris's water maze, both donepezil-loaded NPs and free donepezil groups found the platform in shorter time compared to Aß Alzheimer group. In locomotor activity test, both donepezil treated groups moved less than the Aß Alzheimer group and naïve controls. After the pharmacological experiments, acetylcholinesterase activity was determined and showed an increase in Aß Alzheimer group compared to controls. Donepezil-loaded NPs inhibited the acetylcholinesterase activity more efficiently than the free donepezil group. Conclusion: Targeting with donepezil-loaded PLGA-b-PEG-NPs increases efficiency, helps to inhibit acetylcholinesterase activity more substantially, improves cognitive decline due to its longer duration of action and destabilizing effect on amyloid fibrils.

Generating Lifetime-Enhanced Microbubbles by Decorating Shells with Silicon Quantum Nano-Dots Using a 3-Series T-Junction Microfluidic Device.

Long-term stability of microbubbles is crucial to their effectiveness. Using a new microfluidic device connecting three T-junction channels of 100 µm in series, stable monodisperse SiQD-loaded bovine serum albumin (BSA) protein microbubbles down to 22.8 ± 1.4 µm in diameter were generated. Fluorescence microscopy confirmed the integration of SiQD on the microbubble surface, which retained the same morphology as those without SiQD. The microbubble diameter and stability in air were manipulated through appropriate selection of T-junction numbers, capillary diameter, liquid flow rate, and BSA and SiQD concentrations. A predictive computational model was developed from the experimental data, and the number of T-junctions was incorporated into this model as one of the variables. It was illustrated that the diameter of the monodisperse microbubbles generated can be tailored by combining up to three T-junctions in series, while the operating parameters were kept constant. Computational modeling of microbubble diameter and stability agreed with experimental data. The lifetime of microbubbles increased with increasing T-junction number and higher concentrations of BSA and SiQD. The present research sheds light on a potential new route employing SiQD and triple T-junctions to form stable, monodisperse, multi-layered, and well-characterized protein and quantum dot-loaded protein microbubbles with enhanced stability for the first time.

Mitochondria-targeted CoQ10 loaded PLGA-b-PEG-TPP nanoparticles: Their effects on mitochondrial functions of COQ8B-/- HK-2 cells.

Coenzyme Q10 (CoQ10) deficiency exhibits signs of multiple organ dysfunctions, particular subtypes present isolated kidney involvement progressing to chronic kidney disease. In these patients, early administration of oral CoQ10 has been shown to decrease proteinuria and to delay development of chronic kidney disease, which suggests that it may have a renoprotective potential in these patients. However, CoQ10 bioavailability in mitochondria is low, therefore its efficacy is limited. We aimed to develop mitochondria-targeted CoQ10 loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol)-triphenylphosphonium nanoparticles (CoQ10-TPP-NPs) that would be more efficient in the treatment of CoQ10 nephropathies. These nanoparticles were found to have a size of approximately 150 nm and a zeta potential of + 20 mV. The entrapment efficiency of the nanoparticles was determined as 40%. Cytotoxicity studies showed no effect on the viability of the human kidney proximal tubule epithelial cells exposed to the nanoparticles. The efficacy of the formulated nanoparticles on in vitro disease model, which was developed in the human kidney proximal tubule epithelial cells by siRNA based silencing of the COQ8B, was evaluated through mitochondrial functions by means of metabolomic analyses. We showed that the treatment of COQ8B-/- cells with mitochondria-targeted nanoparticles was more effective in increasing the tricarboxylic acid cycle rate compared to free-CoQ10. Our formulation would be more effective in treatment of CoQ10-related nephropathies than conventional formulations.

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.

Alleviating the toxicity concerns of antibacterial cinnamon-polycaprolactone biomaterials for healthcare-related biomedical applications.

Fibrous constructs with incorporated cinnamon-extract have previously been shown to have potent antifungal abilities. The question remains to whether these constructs are useful in the prevention of bacterial infections in fiber form and what the antimicrobial effects means in terms of toxicity to the native physiological cells. In this work, cinnamon extract containing poly (ε-caprolactone) (PCL) fibers were successfully manufactured by pressurized gyration and had an average size of ∼2 µm. Cinnamon extract containing PCL fibers were tested against Escherichia coli, Staphylococcus aureus, Methicillin resistant staphylococcus aureus, and Enterococcus faecalis bacterial species to assess their antibacterial capacity; it was found that these fibers were able to reduce viable cell numbers of the bacterial species up to two orders of magnitude lower than the control group. The results of the antibacterial tests were assessed by scanning electron microscopy (SEM). The constructs were also tested under indirect MTT tests where they showed little to no toxicity, similar to the control groups. Additionally, cell viability fluorescent imaging displayed no significant toxicity issues with the fibers, even at their highest tested concentration. Here we present a viable method for the production the non-toxic and naturally abundant cinnamon extracted fibers for numerous biomedical applications.

Assessment of electromechanically stimulated bone marrow stem cells seeded acellular cardiac patch in a rat myocardial infarct model.

In this study, we evaluated cardiomyogenic differentiation of electromechanically stimulated rat bone marrow-derived stem cells (rt-BMSCs) on an acellular bovine pericardium (aBP) and we looked at the functioning of this engineered patch in a rat myocardial infarct (MI) model. aBP was prepared using a detergent-based decellularization procedure followed by rt-BMSCs seeding, and electrical, mechanical, or electromechanical stimulations (3 millisecond pulses of 5 V cm-1at 1 Hz, 5% stretching) to enhance cardiomyogenic differentiation. Furthermore, the electromechanically stimulated patch was applied to the MI region over 3 weeks. After this period, the retrieved patch and infarct region were evaluated for the presence of calcification, inflammatory reaction (CD68), patch to host tissue cell migration, and structural sarcomere protein expressions. In conjunction with any sign of calcification, a higher number of BrdU-labelled cells, and a low level of CD68 positive cells were observed in the infarct region under electromechanically stimulated conditions compared with static conditions. More importantly, MHC, SAC, Troponin T, and N-cad positive cells were observed in both infarct region, and retrieved engineered patch after 3 weeks. In a clear alignment with other results, our developed acellular patch promoted the expression of cardiomyogenic differentiation factors under electromechanical stimulation. Our engineered patch showed a successful integration with the host tissue followed by the cell migration to the infarct region.

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.

Current approaches and future prospects of nanofibers: a special focus on antimicrobial drug delivery.

Antibacterial nanofibers have a great potential for effective treatment of infections. They act as drug reservoir systems that release higher quantities of antibacterial agents/drug in a controlled manner at infection sites and prevent drug resistance, while concomitantly decreasing the systemic toxicity. With this drug delivery system, it is also possible to achieve multiple drug entrapment and also simultaneous or sequential release kinetics at the site of action. Therefore, advances in antibacterial nanofibers as drug delivery systems were overviewed within this article. Recently published data on antibacterial drug delivery was also summarised to provide a view of the current state of art in this field. Although antibacterial use seems to be limited and one can ask that 'what is left to be discovered?'; recent update literatures in this field highlighted the use of nanofibers from very different perspectives. We believe that readers will be benefiting this review for enlightening of novel ideas.

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.

Bacterial cellulose micro-nano fibres for wound healing applications.

Bacterial cellulose (BC) is cellulose produced by a few limited species of bacteria in given conditions. BC has many remarkable properties such as its attractive mechanical properties, water uptake ability and biocompatibility which makes it a very desirable material to be used for wound healing. Inherently due to these important properties, the material is very resistant to easy processing and thus difficult to produce into useful entities. Additionally, being rate limited by the dependency on bacterial production, high yield is difficult to obtain and thus secondary material processing is sought after. In this review, BC is explained in terms of synthesis, structure and properties. These beneficial properties are directly related to the material's great potential in wound healing where it has also been trialled commercially but ultimately failed due to processing issues. However, more recently there has been increased frequency in scientific work relating to BC processing into hybrid polymeric fibres using common laboratory fibre forming techniques such as electrospinning and pressurised gyration. This paper summarises current progress in BC fibre manufacturing, its downfalls and also gives a future perspective on how the landscape should change to allow BC to be utilised in wound care in the current environment.

Liposome-based combination therapy for acne treatment.

Acne vulgaris is one of the most common chronic diseases worldwide with the high prevalence ratio of about 80-85% in patients who are in puberty period. For the treatment options, many conventional dosage forms are available; however, existing limitations of systemic administration of drugs (oral antibiotics), such as adverse events and resistance, led for seek of new formulation options. In this study, liposomes containing tetracycline HCl and tretinoin were prepared by the film formation method. In vitro characterization studies revealed that liposomes (111.10 ± 8.02 nm; P.D.I.=0.198 ± 0.03; Z.P.=25.83 ± 0.40 mV) with an encapsulation efficiency more than 80% for both APIs were formulated. In order to maintain a suitable viscosity for topical application, optimized liposomal formulations were dispersed in carbopol-based gel. In vitro release of APIs was sustained for 24 hours with released amounts of 56.44% and 58.44% for tetracycline HCl and tretinoin, respectively. Stability evaluation of both liposomes and liposomes in hydrogels was investigated for 6 months at 4 °C and 25 °C; and no statistically significant change was observed in terms of particle size, zeta potential, encapsulation efficiency, appearance, pH, and viscosity. Cytotoxicity tests confirmed the nontoxic structure of liposomal gel formulations on mice fibroblast cells. In addition, antibacterial efficacy has been proven with Staphylococcus aureus and Streptococcus epidermidis strains as well as the effect on biofilm formation and eradication. As a result, we hereby presented a new combination drug product, which consists of dual active ingredients having comedolytic and bacteriostatic effects in a single, safe, and stable liposome formulation.

Self-assembled micro-stripe patterning of sessile polymeric nanofluid droplets.

When sessile nanofluid droplets evaporate, solid nanoparticles can be organized in a wide variety of patterns on the substrate. The composition of the nanofluid, internal flow type of droplet and the rate of drying affect drop geometry, and the final pattern. Using poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)(PLGA-b-PEG) as the example, we produced micro-stripe patterning from nanoparticles by drying of sessile fluid droplets. We investigated the nanoparticle properties and flow dynamics to clarify their effects on the patterning. Nanoparticles were prepared by hydrodynamic flow focusing using a T-junction microfluidic device with high production efficiency and the ability to generate an extremely narrow size distribution. PLGA-b-PEG was prepared as oil phase in acetonitrile and water/oil flow rate was changed from 1 to 3 at constant oil phase flow rate (50 µL/min). Then, nanofluid was collected on the surface as sessile droplets within acetonitrile/water binary dispersed phase. Depending on size, charge and size-distribution, the nanoparticles deposited on the surface exhibited various patterns. Dynamic Light and X-ray Scattering measurements showed that, approximately 100 nm particles with relatively low PDI (0.04) were produced for the first time in surfactant free conditions in a microfluidic device and they generated self-assembled ordered patterns, which are regulated by the type of internal flow in the sessile nanofluid droplet during sequential evaporation of acetonitrile and water.

Gel network comprising UV crosslinked PLGA-b-PEG-MA nanoparticles for ibuprofen topical delivery.

Ibuprofen is a non-steroidal anti-inflammatory drug for the treatment of Rheumatoid Arthritis and osteoarthritis. In this study, we prepared topical gel network for enhancement of ibuprofen penetration, maintenance of controlled release and increased patient compliance. Nanoparticles containing ibuprofen were prepared by means of emulsion formation/solvent diffusion method using synthesized copolymer. Nanoparticles were then conjugated with aminoethylmethacrylate, resulting in ibuprofen-loaded nanoparticles in PLGA-b-PEG-MA structure. Ibuprofen-loaded gel networks were developed by crosslinking nanoparticles via UV exposure. Suitability for topical application has been assessed through characterization of particle size, zeta potential, morphology, encapsulation efficiency, in vitro release, cytotoxicity and enhancement of in vitro wound healing. The mean diameter of nanoparticles was measured as 230 ± 20 nm. Gel network formulations with higher particle size (2800 ± 350 nm) and zeta potential (39.8 ± 9.2 mV), depending on conjugation of methacrylate within copolymeric structure, and having encapsulation efficacy of 73.6 ± 2.8% were prepared. The in vitro release of ibuprofen was sustained for more than 7 hours. Gel network improved collagen synthesis, type I collagen mRNA expression and fibrosis in dose dependent manner. Based on this, we can conclude that PLGA-b-PEG gel network might be a promising systems for the local delivery of ibuprofen in RA patients.

Honeycomb-like PLGA- b-PEG Structure Creation with T-Junction Microdroplets.

Amphiphilic block copolymers are widely used in science owing to their versatile properties. In this study, amphiphilic block copolymer poly(lactic- co-glycolic acid)- block-poly(ethylene glycol) (PLGA- b-PEG) was used to create microdroplets in a T-junction microfluidic device with a well-defined geometry. To compare interfacial characteristics of microdroplets, dichloromethane (DCM) and chloroform were used to prepare PLGA- b-PEG solution as an oil phase. In the T-junction device, water and oil phases were manipulated at variable flow rates from 50 to 300 µL/min by increments of 50 µL/min. Fabricated microdroplets were directly collected on a glass slide. After a drying period, porous two-dimensional and three-dimensional structures were obtained as honeycomb-like structure. Pore sizes were increased according to increased water/oil flow rate for both DCM and chloroform solutions. Also, it was shown that increasing polymer concentration decreased the pore size of honeycomb-like structures at a constant water/oil flow rate (50:50 µL/min). Additionally, PLGA- b-PEG nanoparticles were also obtained on the struts of honeycomb-like structures according to the water solubility, volatility, and viscosity properties of oil phases, by the aid of Marangoni flow. The resulting structures have a great potential to be used in biomedical applications, especially in drug delivery-related studies, with nanoparticle forming ability and cellular responses in different surface morphologies.

Gold nano-decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation.

Neurite outgrowth and elongation of neural cells is the most important subject that is considered in nerve tissue engineering. In this regard, aligned nanofibers have taken much attention in terms of providing guidance for newly outgrown neurites. The main objective of this study was to fabricate aligned polyurethane nanofibers by electrospinning process and decorate them with gold nanoparticles to further investigate the synergistic effects of nanotopography, biological nerve growth factor (NGF) and electrical stimulations on neurite outgrowth and elongation of pheochromocytoma (PC-12) model cells. In this regard, smooth and uniform aligned polyurethane nanofibers with the average diameter of 519 ± 56 nm were fabricated and decorated with the gold nanoparticles with the average diameter of ∼50 nm. PC-12 cells were cultured on the various nanofiber surfaces inside the bio-mimetic bioreactor system and exposed either to NGF alone or combination of NGF and electrical stimulation. It was found that 50 ng/mL NGF concentration is an optimal value for the stimulation of neurite outgrowth. After 4 days of culture under 100 mV, 10 ms electrical stimulation in 1 h/day period it was found that the gold nanoparticle decorated aligned polyurethane nanofibers increased the neurite outgrowth and elongation more with the combinational NGF and electrical stimulation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1604-1613, 2018.

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.

Donepezil loaded PLGA-b-PEG nanoparticles: their ability to induce destabilization of amyloid fibrils and to cross blood brain barrier in vitro.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Cholinesterase inhibitors (ChEIs) are commonly used for symptomatic treatment of neural transmission improvement in AD. Donepezil is a reversible and non-competitive ChEI which is clinically used for palliative treatment of AD. The aim of the present study was to investigate the destabilizing effect of donepezil loaded poly(lactic-co-glycolic acid)-block-poly (ethylene glycol) [PLGA-b-PEG] nanoparticles on fibril formation in vitro and the ability of these nanoparticles to cross blood brain barrier (BBB) using in vitro BBB model and the neuroprotective effects of free donepezil and donepezil loaded PLGA-b-PEG nanoparticles. Donepezil loaded PLGA-b-PEG nanoparticles were prepared with double emulsion method. Destabilizing effect of these donepezil loaded particles on the amyloid-beta fibril (Aß1-40 and Aß1-42) formation was determined in vitro. Nanoparticles were found to have small particle size and have destabilizing effect on fibril formation. In vitro BBB model was successfully prepared. Nanoparticles showed the ability to cross the BBB and showed a controlled release profile in this system. IL-1ß, IL-6, GM-CSF, TGF-ß, MCP-1 and TNF-α levels were found to be increased in both gene and protein expression levels in astrocytes incubated with amyloid fibrils in in vitro BBB model suggesting an increased inflammation. Free donepezil and donepezil loaded nanoparticle administration caused a significant dose-dependent decrease in both gene and protein expression levels of IL-1ß, IL-6, GM-CSF and TNF-α. No significant changes were observed for TGF-ß and MCP-1.

Polyethyleneimine brushes effectively inhibit encrustation on polyurethane ureteral stents both in dynamic bioreactor and in vivo.

Polyurethane (PU) ureteral stents have been widely used as biomedical devices to aid the flow of the urine. Due to the biofilm formation and encrustation complications it has been hindered their long term clinical usage. To overcome these complications, in this study, cationic polyethyleneimine (PEI) brushes grafted on PU stents and their performances were tested both in a dynamic biofilm reactor system (in vitro) and in a rat model (in vivo). Thus, we hypothesized that PEI brushes inhibit bacterial adhesion owing to the dynamic motion of brushes in liquid environment. In addition, cationic structure of PEI disrupts the membrane and so kills the bacteria on time of contact. Cationic PEI brushes decreased the biofilm formation up to 2 orders of magnitude and approximately 50% of encrustation amount in respect to unmodified PU, in vitro. In addition, according to Atomic Absorption Spectroscopy (AAS) results, approximately 90% of encrustation was inhibited on in vivo animal models. Decrease in encrustation was clearly observed on the stents obtained from rat model, by Scanning Electron Microscopy (SEM). Also, histological evaluations showed that; PEI brush grafting decreased host tissue inflammation in close relation to decrease in biofilm formation and encrustation. As a results; dual effect of anti-adhesive and contact-killing antibacterial strategy showed high efficiency on PEI brushes grafted PU stents both in vitro and in vivo.