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Biodegradable polyesters are a popular choice for both packaging and medical device manufacture owing to their ability to break down into harmless components once they have completed their function. However, commonly used polyesters such as poly(hydroxybutyrate) (PHB), poly(lactic acid) (PLA), and polycaprolactone (PCL), while readily available and have a relatively low price compared to other biodegradable polyesters, do not meet the degradation profiles required for many applications. As such, this study aimed to determine if the mechanical and degradation properties of biodegradable polymers could be tailored by blending different polymers. The seawater degradation mechanisms were evaluated, revealing surface erosion and bulk degradation in the blends. The extent of degradation was found to be dependent on the specific chemical composition of the polymer and the blend ratio, with degradation occurring via hydrolytic, enzymatic, oxidative, or physical pathways. PLA presents the highest tensile strength (67 MPa); the addition of PHB and PCL increased the flexibility of the samples; however, the tensile strength reduced to 25.5 and 18 MPa for the blends 30/50/20 and 50/25/25, respectively. Additionally, PCL presented weight loss of up to 10 wt.% and PHB of up to 6 wt.%; the seawater degradation in the blends occurs by bulk and surface erosion. The blending process facilitated the flexibility of the blends, enabling their use in diverse industrial applications such as medical devices and packaging. The proposed methodology produced biodegradable blends with tailored properties within a seawater environment. Additionally, further tests that fully track the biodegradation process should be put in place; incorporating compatibilizers might promote the miscibility of different polymers, improving their mechanical properties and biodegradability.

The increase in pathogen levels in seawater threatens the safety of entire aquatic ecosystems. Foodborne pathogens can potentially accumulate in shellfish, especially in filter feeders such as bivalves, requiring an efficient depuration process before consumption. Alternative approaches to promote a cost-efficient purge at depuration plants are urgently needed. A small prototype pulsed ultraviolet (PUV) light recirculation system was designed, and its depuration potential was tested in a seawater matrix artificially contaminated with high levels of microbial pathogens Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Bacillus cereus and Candida albicans. The analysis of treatment parameters including voltage, number of pulses and duration of treatment was performed to ensure the highest reduction in contaminant levels. Optimal PUV disinfection was attained at 60 pulses/min at 1 kV for 10 min (a UV output of 12.9 J/cm2). All reductions were statistically significant, and the greatest was observed for S. aureus (5.63 log10), followed by C. albicans (5.15 log10), S. typhimurium (5 log10), B. cereus (4.59 log10) and E. coli (4.55 log10). PUV treatment disrupted the pathogen DNA with the result that S. aureus, C. albicans and S. typhimurium were not detectable by PCR. Regulations were reviewed to address the applicability of PUV treatment as a promising alternative to assist in the reduction of microbial pathogens at depuration plants due to its high efficiency, short treatment period, high UV dose and recirculation system as currently employed in shellfish depuration plants.

Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that, due to its inherent bioactivity and extracellular matrix-like structure, has the potential to be utilised extensively in tissue engineering. However, this glycosaminoglycan lacks the properties required for cellular adhesion and photo-crosslinking by UV light, which significantly hinders this polymers applicability. This research presents a method for modifying hyaluronic acid via thiolation and methacrylation to generate a novel photo-crosslinkable polymer with improved physicochemical properties, biocompatibility and the potential to customize biodegradability according to the ratio of monomers used. A decrease in stiffness proportional to increasing thiol concentration was observed when testing the compressive strength of hydrogels. Conversely, it was noted that the storage moduli of hydrogels increased proportionally to thiol concentration indicating a greater degree of cross-linking with the addition of thiol. The addition of thiol to HA increased the biocompatibility of the material in both neuronal and glial cell lines and improved the degradability of methacrylated HA. Due to the enhanced physicochemical properties and biocompatibility imparted by the introduction of thiolated HA, this novel hydrogel system could have numerous bioengineering applications. yes

Poly (lactic acid)/halloysite nanotube (PLA/HNT) nanocomposites have been studied extensively over the past few years owing to the interesting properties of the polymer, PLA, and the nanoclay, HNT, individually and as composites. In this paper, the influence of the screw speed during extrusion was investigated and was found to have a significant impact on the mechanical and thermal performance of the extruded PLA/HNT nanocomposites. To determine the effect of screw speed on PLA/HNT nanocomposites, 5 and 10 wt% of HNTs were blended into the PLA matrix through compounding at screw speeds of 40, 80, and 140 rpm. Virgin PLA was compounded for comparison. The resultant polymer melt was quench cooled onto a calendar system to produce composite films which were assessed for mechanical, thermal, chemical, and surface properties. Results illustrate that in comparison to 40 and 80 rpm, the virgin PLA when compounded at 140 rpm, indicated a significant increase in the mechanical properties. The PLA/HNT 5 wt% nanocomposite compounded at 140 rpm showed significant improvement in the dispersion of HNTs in the PLA matrix which in turn enhanced the mechanical and thermal properties. This can be attributed to the increased melt shear at higher screw speeds.

Acute respiratory distress syndrome (ARDS) is the most common form of acute severe hypoxemic respiratory failure in the critically ill with a hospital mortality of 40%. Alveolar inflammation is one of the hallmarks for this disease. β-Glucans are polysaccharides isolated from a variety of natural sources including mushrooms, with documented immune modulating properties. To investigate the immunomodulatory activity of β-glucans and their potential as a treatment for ARDS, we isolated and measured glucan-rich polysaccharides from seven species of mushrooms. We used three models of in-vitro injury in THP-1 macrophages, Peripheral blood mononuclear cells (CD14+) (PMBCs) isolated from healthy volunteers and lung epithelial cell lines. We observed variance between β-glucan content in extracts isolated from seven mushroom species. The extracts with the highest β-glucan content found was Lentinus edodes which contained 70% w/w and Hypsizygus tessellatus which contained 80% w/w with low levels of α-glucan. The extracts had the ability to induce secretion of up to 4000 pg/mL of the inflammatory cytokine IL-6, and up to 5000 pg/mL and 500 pg/mL of the anti-inflammatory cytokines IL-22 and IL-10, respectively, at a concentration of 1 mg/mL in THP-1 macrophages. In the presence of cytokine injury, IL-8 was reduced from 15,000 pg/mL to as low as 10,000 pg/mL in THP-1 macrophages. After insult with LPS, phagocytosis dropped from 70–90% to as low 10% in CD14+ PBMCs. After LPS insult CCL8 relative gene expression was reduced, and IL-10 relative gene expression increased from 50 to 250-fold in THP-1 macrophages. In lung epithelial cells, both A549 and BEAS-2B after IL-1β insult, IL-8 levels dropped from 10,000 pg/mL to as low as 6000 pg/mL. TNF-α levels dropped 10-fold from 100 pg/mL to just below 10 pg/mL. These results demonstrate the therapeutic potential of β-glucans in inflammatory lung conditions. Findings also advance bio-based research that connects green innovation with One Health applications for the betterment of society. yes

The industrial use of additive manufacturing continues to rapidly increase as new technology developments become available. The Arburg plastic freeforming (APF) process is designed to utilize standard polymeric granules in order to print parts with properties similar to those of molded parts. Despite the emerging industrial importance of APF, the current body of knowledge regarding this technology is still very limited, especially in the field of biodegradable polymer composites. To this end, poly(lactic acid) (PLA) was reinforced with halloysite nanotubes (HNTs) by hot melt extrusion. The PLA/HNT (0–10 wt%.) composites were analyzed in terms of their rheology, morphology, and thermal and mechanical properties. A study of the processing properties of these composites in the context of APF was performed to ensure the consistency of 3D-printed, high-quality components. The optimized machine settings were used to evaluate the tensile properties of specimens printed with different axis orientations (XY and XZ) and deposition angles (0 and 45°). Specimens printed with an XY orientation and deposition angle starting at 0° resulted in the highest mechanical properties. In this study, the use of PLA/HNT composites in an APF process was reported for the first time, and the current methodology achieved satisfactory results in terms of the 3D printing and evaluation of successful PLA/HNT composites to be used as feedstock in an APF process.

Antimicrobial resistance (AMR) is recognised globally as one of the greatest threats to human and animal health; thus, discovery of alternative antibacterial agents to address AMR is a priority challenge. This study constitutes the first report of a low-melting temperature, polymer- extrusion process for the smart delivery of thermally-sensitive antimicrobial bioactives, including generally-regarded-as-safe (GRAS) bioactives derived from various sources. Bioactives were assessed before and after extrusion by determining their respective minimum inhibitory concentrations (MIC). WHO-priority AMR-bacterial isolates causing zoonotic infections were evaluated along with use of standard ATCC strains. Findings revealed that this copolymer method was capable of delivering thermally-sensitive bioactives with varying degrees of growth inhibition against the AMR-bacterial strains. The extrusion process was found to increase the effect of nisin against MRSA (4-fold increase) and L. monocytogenes (6.4-fold increase), silver nitrate (AgNO3) against E. coli (3.6-fold increase) and S. epidermidis (1.25-fold increase), and chitosan against S. aureus (1.25-fold). Findings show the potential applicability of this polymer extrusion process for developing future bioactive-loaded polymer compounds; thus, highlighting the potential of converging bio-based industry with novel materials for enabling ‘One-Health’ solutions. yes

Oral tablets are a convenient form to deliver active pharmaceutical ingredients (API) and have a high level of acceptance from clinicians and patients. There is a wide range of excipients available for the fabrication of tablets thereby offering a versatile platform for the delivery of therapeutic agents to the gastrointestinal tract. However, the geometry of tablets is limited by conventional manufacturing processes. This study aimed to compare three manufacturing processes in the production of flat-faced oral tablets using the same formulation composed of a polymer blend and caffeine as a model drug: fused-filament fabrication (FFF), direct compression (DC) and injection molding (IM). Hot-melt extrusion was used to convert a powder blend into feedstock material for FFF and IM processes, while DC was performed on the powder mixture. Tablets were produced with the same dimensions and were characterized for their physical and dissolution properties. There were statistical differences in the physical properties and drug release profiles of the tablets produced by the different manufacturing processes. DC tablets displayed immediate release, IM provided sustained release over 48 h, and FFF tablets displayed both release types depending on the printing parameters. FFF continues to demonstrate high potential as a manufacturing process for the efficient production of personalized oral tablets.

Calcium carbonate (CaCO3) is frequently added to polyethylene (PE) as a filler to reduce costs. An alternative to CaCO3, calcium fluoride (CaF2) was proposed in this research. PE/CaCO3 and PE/CaF2 composites in a wide composition range (0–60 wt.%) were prepared through a parallel twin screw extruder. Results indicated better interaction of CaF2 with PE matrix which improved samples yield stress. Statistical analysis showed the filler type was more influential factor on the yield stress while filler loading was not a statistically significant one. In contrast, crystallinity was strongly depended on the filler loading. The dynamic mechanical and rheological investigations revealed that PE/CaF2 composites had higher stiffness at ambient temperature and possessed lower viscosity below 40 wt.% of filler loading compared to PE/CaCO3 which could reduce the processing cost. Therefore, regarding its low price and good functional properties, CaF2 can be a promising alternative to CaCO3.

Introduction/Background Cervical cancer (CC) is described as cancer that occurs in the cells located in the cervix. Each year, more than 500,000 women are diagnosed with CC and the disease results in over 300,000 deaths across the world. Infection by high-risk oncogenic subtypes of human papillomavirus (HPV); HPV16 and HPV18, is the cause for almost all cases of CC. In developed countries, CC incidence and mortality have more than halved over the past 30 years as they were able to establish successful national HPV screening and vaccination programs. However, this disease remains persistent and has become one of the leading causes of death among women in developing (low to middle-income) countries; mostly in African countries. Adapting to low resources, developing countries have practiced a feasible and cost-effective solutions with the screen and treat approach instead. Screening usually involves visual inspection with acetic acid (VIA) or Lugol’s iodine (VILI) that gives immediate results, facilitating instantaneous treatment strategies and prevents loss to follow-up. Treatments includes loop electrosurgical excision procedure (LEEP), cryotherapy or cold-knife conization. This research proposes the development of a self-administered chemotherapeutic vaginal tablet formulation that would complement these current treatment strategies. Methodology The bilayer tablets were prepared one layer at a time, using a single punch direct compression machine. Tablets were then evaluated using the pharmacopeial guideline that include tablet uniformity, hardness, friability and content uniformity. Swelling test was performed by simple immersion of the tablets in dissolution medium for 24 hours, the tablet’s weight before and after were recorded. The drug release profile was evaluated by in vitro drug dissolution test using the USP paddle method in 2% aqueous sodium dodecyl sulphate (SDS) solution; maintained at 100rpm, 37±1°C and in sink conditions. All samples were measured spectroscopically. Cell viability after treatment with the drugs was determined using the MTT assay on Ca-ski cells. Results Results showed that the tablet of this combination are uniform and durable in compliance to pharmacopeial standards, a swelling study shows promising potential for mucoadhesion and has an extended in vitro drug release profile over 72 hours. In vitro cell culture with Ca-Ski cells however, did not show a synergistic effect but only a small additive effect was observed. Conclusion A vaginal tablet offers an easy application and direct localized access to the cervix; adjacent to the cancerous tissue. The advantages of vaginal drug delivery include (i) bypassing hepatic first pass-effect; (ii) low systemic drug exposure; and (iii) higher bioavailability. A bilayer tablet provides an opportunity to deliver two active pharmaceutical ingredients (API) simultaneously for a synergistic pharmacological effect. Additionally, the different layers physically avoid chemical incompatibilities. Chitosan and polyacrylic acid are the polymers employed for their mucoadhesive property. These polymers also provide an extended and a controlled drug release rate. 5-fluorouracil (5FU) a drug developed and used for the treatment of cancer for more than 50 years was selected as the primary API. Cell studies showed the first combination formulated; 5FU and disulfiram did not show a synergistic effect. Other API will be investigated in combination with 5FU in order to achieve the synergistic effect desired. Disclosures The authors declare no conflict of interests.

Bacterial infection remains the main cause of acute respiratory distress syndrome and is a leading cause of death and disability in critically ill patients Here we report on the use of purified beta-glucan (lentinan) extracts from Lentinus edodes (Shiitake) mushroom that can reduce infection by a multidrug-resistant clinical isolate of Klebsiella pneumoniae in a rodent pneumonia model, likely through immunomodulation Adult male Sprague-Dawley rats were subjected to intra-tracheal administration of K pneumoniae to induce pulmonary sepsis and randomized to three groups;vehicle control (Vehicle, n = 12), commercial lentinan (CL, n = 8) or in-house extracted lentinan (IHL, n = 8) were administered intravenously 1 h postinfection Physiological parameters and blood gas analysis were measured, bacterial counts from bronchoalveolar-lavage (BAL) were determined, along with differential staining of white cells and measurement of protein concentration in BAL 48 h after pneumonia induction Use of IHL extract significantly decreased BAL CFU counts Both CL and IHL extractions reduced protein concentration in BAL Use of IHL resulted in an improvement in physiological parameters compared to controls and CL In conclusion, administration of lentinan to treat sepsis-induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner

Implantable drug delivery systems provide extended release of a drug for the desired duration, usually over timespans of months and years. A broad range of materials are currently in use for the fabrication of implants, both nondegradable and biodegradable, the choice of which will depend on the drug being delivered, the type and length of drug release required, and whether or not the device can remain in place permanently. However, as all implants are exposed to tissues for prolonged periods, it is essential that each material is biocompatible to reduce undesirable cytotoxic effects. There are a wide variety of implantable devices in clinical use including subdermal implants, vaginal rings, intrauterine devices, ocular implants, and intracerebral implants. This chapter will discuss the use of both nondegradable and biodegradable materials for the manufacture of implantable drug delivery systems with an overview of how each type of material has been utilized in the production of experimental, patented, and/or marketed implantable drug delivery systems.

This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a very common formulation that is easy to manufacture, easy to place in the vagina, and has a low cost of manufacture, making them ideal for use in developing countries. A combination of disulfiram and 5-fluorouracil, which are both off-patent drugs and provide different modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, differential scanning calorimetry (DSC), particle morphology, in vitro drug release, and cytotoxicity on Ca-Ski cells. Both layers were designed to release both drugs concurrently for a synergistic effect. The polymer&ndash, polymer interaction between the layers was able to reduce the loss of formulation due to chitosan. While the bilayer tablet had satisfactory performance in the physicochemical tests, in vitro cell culture with Ca-Ski also showed a synergistic effect using a combination of drugs at a low dose. However, the formulation only had 24-h dose release before degradation. Further drug combinations should be evaluated in subsequent studies.

Catalytic graphitization of biocarbon prepared from Miscanthus grass was possible through chemical treatment with iron(III) nitrate, Fe(NO3)3, and cobalt(II) nitrate, Co(NO3)2. The pyrolysis monitoring, until the temperature of 900 °C, permitted for the primary analysis of the effects of the generated catalysis species on biomass degradation. Then both Raman spectroscopy and X-ray diffraction (XRD) allowed for the observation of microstructural changes between the samples treated with metal catalysts and the untreated samples. The samples treated with both iron and cobalt nitrates are twice as efficient at forming ordered graphite than the treated sample with the catalysts used separately. This may be due to FeCo nanoparticles generated in situ during pyrolysis. These results show that the morphology and allotropy of renewable biocarbon can be tailored in such a way that it can be applied to design smart materials.

Cervical cancer is usually treated by surgery, with the more advanced cancers requiring adjuvant chemotherapy or radiotherapy. The location of the cervix makes it easily accessible through the vagina for the localised delivery of chemotherapeutic drugs. Localised delivery has the advantage of direct delivery to the site of action resulting in a lower dose having to be required and a reduction in systemic side effects. This approach would be advantageous for fertility sparing surgery, whereby localised delivery could be used to reduce tumour size allowing for a much smaller tumour to be removed, reducing the risk of preterm birth. Furthermore, localised delivery could be used after surgery to reduce the risk of recurrence, which is significantly higher in fertility sparing surgery compared to standard surgery. In this paper, we discuss the number of vaginal dosage forms that have investigated for this purpose, including tablets, rings, bioadhesive and cervical caps. APIs under investigation have ranged from well-established chemotherapeutic drugs to more experimental compounds. yes

Poly-l-lactic acid (PLLA) is one of the most common bioabsorbable materials in the medical device field. However, its use in load-bearing applications is limited due to its inferior mechanical properties when compared to many of the competing metal-based permanent and bioabsorbable materials. The objective of this study was to directly compare the influence of both annealing and biaxial expansion processes to improve the material properties of PLLA. Results showed that both annealing and biaxial expansion led to an overall increase in crystallinity and that the crystallites formed during both processes were in the &alpha, &rsquo, and &alpha, forms. 2D-WAXS patterns showed that the preferred orientation of crystallites formed during annealing was parallel to the circumferential direction. While biaxial expansion resulted in orientation in both axial and circumferential directions, with relatively equal sized crystals in both directions, Da (112 &Aring, ) and Dc (97 &Aring, ). The expansion process had the most profound effect on mechanical performance, with a 65% increase in Young&rsquo, s modulus, a 45% increase in maximum tensile stress and an 18-fold increase in strain at maximum load. These results indicate that biaxially expanding PLLA at a temperature above Tcc is possible, due to the high strain rates associated with stretch blow moulding.

The new frontier of medicine is the personalization of treatment to match a patient’s individual needs. Fused-filament fabrication (FFF) offers a platform for the personalization of drug dosage forms, but one of its chief shortcomings compared to other tablet production methods such as dry compression and wet granulation is relatively low throughput. Conversely, injection molding (IM) is a manufacturing technique for the high-volume production of parts, but in which individual part customization is both expensive and slow requiring the modification of expensive mold tooling. Mass-customization is the manufacture of custom products that match the needs of individual consumers but which are produced at the low unit cost associated with high-volume production. We successfully integrated for the first time FFF with IM in a multi-step manufacturing process for the production of custom bilayer tablets loaded with two active pharmaceutical ingredients used in the treatment of cardiovascular disease. The FFF layer was loaded with the diuretic hydrochlorothiazide, while the IM layer was loaded with lovastatin. Infill percentage was varied for the FFF layer as a means to modify drug release. The IM injection pressure was evaluated for its effect on drug release and layer-layer adhesion. The bilayer tablets obtained offered different combinations of drug release profiles, which were governed by a combination of factors, including surface area to volume ratio; IM injection volume penetration into the FFF layer; FFF infill percentage; layer tortuosity and porosity. These different parameters could be utilized to modify the individual release of both drugs from the bilayer tablet. Thus for the first time, we have demonstrated a viable method for the mass-customization of oral tablets which could hasten the rollout of personalized medicine. yes

Rationale: Acute Respiratory Distress Syndrome (ARDS) is characterized by an acute lung inflammatory process. This results in lung parenchyma injury and promotes activation of the immune system with the up-regulation of pro-inflammatory cytokines. β-glucans - a diverse group of polysaccharides - have been reported to have immune-modulating properties which could have the potential to regulate the cytokine cascade during ARDS. A pure β-glucan compound is required. However, mass produced commercial products contain various contaminants including α-glucans, that might affect the active immune-modulating component. We performed a novel extraction process to achieve a pure β-glucan compound, determined by megazyme analysis kit. We hypothesized that the purer sample would have an increased immunomodulatory activity in different cell lines, including pulmonary type II alveolar cell line (A549), compared to a commercial source β-glucan. Methods: Lentinan is a β-glucan extracted from the mushroom Lentinus edodes. Commercial Lentinan (CL) was purchased as a sterile powder from Carbosynth Ltd, UK. In-house Lentinan (IHL) was extracted from crude mushroom using a proprietary process. Cells exposed to both extracts comprised of pulmonary type II alveolar cell line (A549), human monocytic cells (THP-1) and human mesenchymal stem cells derived from bone marrow (BM-MSCs). Assays carried out included cytotoxicity, phagocytosis and luciferase to determine inflammation via NF-kB pathway and analysis of cytokine release profile using Enzyme Linked Immuno Sorbent Assay. Test series were carried out to determine potential preliminary in-vitro activity of the novel IHL extract. Results: IHL extract contained a higher percentage of β-glucans and lower levels of α-glucans compared to CL. Both extracts demonstrated low to minimal toxicity in all cell lines. Both extracts significantly reduced percentage phagocytic index in lipopolysaccharide injured and non-injured phorbol-12-myristate-13-acetate activated THP-1 cells. A reduction in inflammation was observed with both IHL and CL in IL-1β injured A549 cells determined with IL-8 expression and luciferase assay. IHL and CL had no effect on the expression of IL-8 and IL-6 in BM-MSCs and THP-1. IHL increased levels of IL-1 and TNF-α in THP-1. Both β-glucans extracts increased release of VEGF in BM-MSCs. Conclusions: We reported that the novel IHL is a purer β-glucan extract from Lentinan edodes compared to CL, with no contaminating α-glucans. We observed that IHL and CL had both inflammatory and antiinflammatory properties, with IHL showing a greater immune-modulating profile compared to CL. Further investigations about immunomodulation potential of this novel extract are required in future in-vivo studies.

Biodegradable polymers play a crucial role in the medical device field, with a broad range of applications such as suturing, drug delivery, tissue engineering, scaffolding, orthopaedics, and fixation devices. Poly-l-lactic acid (PLLA) is one of the most commonly used and investigated biodegradable polymers. The objective of this study was to determine the influence low shear microbore extrusion exerts on the properties of high molecular weight PLLA for medical tubing applications. Results showed that even at low shear rates there was a considerable reduction in molecular weight (Mn = 7&ndash, 18%) during processing, with a further loss (Mn 11%) associated with resin drying. An increase in melt residence time from ~4 mins to ~6 mins, translated into a 12% greater reduction in molecular weight. The degradation mechanism was determined to be thermal and resulted in a ~22-fold increase in residual monomer. The differences in molecular weight between both batches had no effect on the materials thermal or morphological properties. However, it did affect its mechanical properties, with a significant impact on tensile strength and modulus. Interestingly there was no effect on the elongational proprieties of the tubing. There was also an observed temperature-dependence of mechanical properties below the glass transition temperature.