The Development of a Melt-Extruded Shellac Carrier for the Targeted Delivery of Probiotics to the Colon

Hot melt extrusion (HME) is considered an efficient technique in developing solid molecular dispersions, and has been demonstrated to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. However, most commercial enteric or pH-responsive polymers are relatively difficult to process or have high Glass Transition Temperature (Tg) values, making their use with temperature-sensitive drugs, probiotics or biologics not viable. Shellac is a natural thermoplastic, and after a review of current literature on the pharmaceutical HME process, a possible gap in the knowledge of the use of shellac to produce dosage forms by means of HME was identified. This work explores the possibility of SSB® 55 pharmaceutical-grade shellac as a melt-extrudable encapsulation polymer to entrap freeze-dried probiotic powder and to determine bacterial cell viability post-processing. Well-defined strands were produced from the physical mixture of shellac and Biocare® Bifidobacterium Probiotic. FTIR clarified that there are no significant interactions between the probiotic and polymer. All of the samples demonstrated less than 5% degradation over 24 h at pH of both 1.2 and 6.8. At pH 7.4, both loaded samples gave a similar dissolution trend with complete degradation achieved after 10–11 h. Following five-month storage, 57.8% reduction in viability was observed

Physical Properties of Shellac Material Used for Hot Melt Extrusion with Potential Application in the Pharmaceutical Industry

Hot melt extrusion offers an efficient way of increasing the solubility of a poorly soluble drug. Shellac has potential as a pharmaceutical matrix polymer that can be used in this extrusion process, with further advantages for use in enteric drug delivery systems. The rheological property of a material affects the extrusion process conditions. However, the literature does not refer to any published work that investigates the processability of various shellac materials. This work explores various types of shellac and explores their physicochemical and thermal properties along with their processability in the hot melt extrusion application. Physicochemical characterization of the materials was achieved using differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Additional processability characterization was achieved using melt flow index and rheology analysis. The results indicated that there was no chemical difference between the various shellac types compared in this study. However, the extrudable temperature ranges and rheological properties of different shellac types varied; SSB 55 Pharma FL had the lowest processing temperature and glass transition temperatures. Due to the shear-thinning behaviours, shellac can be extruded at lower temperatures. This study provides necessary data to determine the processing conditions in hot melt extrusion applications for the range of shellac materials

Process Optimization for the 3D Printing of PLA and HNT Composites with Arburg Plastic Freeforming

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

Process Optimization for the 3D Printing of PLA and HNT Composites with Arburg Plastic Freeforming

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

The Influence of Low Shear Microbore Extrusion on the Properties of High Molecular Weight Poly(<span style="font-variant: small-caps">l</span>-Lactic Acid) for Medical Tubing Applications

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&#8211;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

The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin

Angiostatin, a potent naturally occurring inhibitor of angiogenesis and growth of tumor metastases, is generated by cancer-mediated proteolysis of plasminogen. Human prostate carcinoma cells (PC-3) release enzymatic activity that converts plasminogen to angiostatin. We have now identified two components released by PC-3 cells, urokinase (uPA) and free sulfhydryl donors (FSDs), that are sufficient for angiostatin generation. Furthermore, in a defined cell-free system, plasminogen activators [uPA, tissue-type plasminogen activator (tPA), or streptokinase], in combination with one of a series of FSDs (N-acetyl-l-cysteine, d-penicillamine, captopril, l-cysteine, or reduced glutathione] generate angiostatin from plasminogen. An essential role of plasmin catalytic activity for angiostatin generation was identified by using recombinant mutant plasminogens as substrates. The wild-type recombinant plasminogen was converted to angiostatin in the setting of uPA/FSD; however, a plasminogen activation site mutant and a catalytically inactive mutant failed to generate angiostatin. Cell-free derived angiostatin inhibited angiogenesis in vitro and in vivo and suppressed the growth of Lewis lung carcinoma metastases. These findings define a direct mechanism for cancer-cell-mediated angiostatin generation and permit large-scale production of bioactive angiostatin for investigation and potential therapeutic application

Fulfilling global marine commitments; lessons learned from Gabon

As part of the Post-2020 Biodiversity Framework, nations are assessing progress over the past decade in addressing the underlying drivers that influence direct pressures on biodiversity and formulating new policies and strategies for the decade to come. For marine conservation, global marine protected area (MPA) coverage is still falling short of the 10% target set in 2010. Here we show that while this reflects a lack of progress in many low- and middle-income countries, a few of these nations have met or exceeded international commitments. To provide an in-depth explanation of how this was achieved in Gabon, we summarize the lessons learnt by our consortium of policy makers and practitioners who helped implement a comprehensive and ecologically representative network of 20 MPAs. We show the importance of creating a national framework, building long-term stakeholder support, and focusing on research that guides implementation and policy; and outline a four-step approach that countries and donors could use as an example to help meet international commitments. By responding to calls to share lessons learned to inform future Convention on Biological Diversity targets, we show how Gabon's experiences could inform change elsewhere