3D-printing: An emerging and a revolutionary technology in pharmaceuticals

© 2018 EDIZIONI MINERVA MEDICA. One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is three-dimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3D-printing include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3D-printing technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with built-in flexibility for safer and effective therapy. Our mini-review provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences

Chronometry and formation pathways of gypsum using Electron Spin Resonance and Fourier Transform Infrared Spectroscopy

Gypsum is an authigenic precipitate that forms under periods of accentuated aridity and occurs widely in arid zones. However its use in quantitative paleoclimatology has been limited due to the absence of a method to determine the timing of its formation. We present here the results of a feasibility study that demonstrates that the timing of the formation event of gypsum can be estimated using Electron Spin Resonance (ESR) analysis. We used well documented samples from White Sands in New Mexico, USA, the Thar Desert, India and lakes in the Simpson Desert and Mallee Region, Australia and found that ESR ages could be obtained using radiation sensitive SO4-, SO3- radicals and a photobleachable signal O3-. ESR signals were consistent with control ages based on contextual information. These suggest that the dating signals (SO4-, SO3-) are stable over time scales >100 ka. We propose that this stability of the SO4- signals over geological time scales arises due to hydrogen bonding between the water proton and the SO4- radical and that the suitability of these radiation-induced radicals comes from their being a part of the host matrix. Further, ESR along with Fourier Transform Infrared (FT-IR) Spectroscopy methods additionally inform on the geochemical pathways for gypsum formation and help elucidate complex formation processes even in samples that appeared unambiguous gypsum precipitates. Thus, the presence of Hannebachite (CaSO3.1/2H2O) and Mn2+ in Thar and Australian samples suggested a reducing environment such that low valence sulfur reacted with CaCO3 to form hannebachite and eventually gypsum. The presence of sulfur, partially as sulfite in Thar gypsum samples suggested that redox cycles were mediated by microbial activity. Absence of these features in White Sands samples suggested oxic conditions during gypsum precipitation

The potential of siRNA based drug delivery in respiratory disorders: recent advances and progress

© 2019 Wiley Periodicals, Inc. Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases

Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems

© 2018 Elsevier B.V. Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic

Subsurface signatures and timing of extreme wave events along the Southeast Indian coast

Written history's limitation becomes apparent when attempting to document the predecessors of extreme coastal events in the Indian Ocean, from 550-700 years in Thailand and 1000 years in Indonesia. Detailed ground-penetrating radar (GPR) surveys in Mahabalipuram, southeast India, complemented with sedimentological analyses, magnetic susceptibility measurements, and optical dating provide strong evidence of extreme wave events during the past 3700 years. The diagnostic event signatures include the extent and elevation of the deposits, as well as morphologic similarity of buried erosional scarps to those reported in northern Sumatra region. Optical ages immediately overlying the imaged discontinuities that coincides with high concentration of heavy minerals date the erosional events to 340 ± 35, 350 ± 20, 490 ± 30, 880 ± 40, 1080 ± 60, 1175 ± 188, 2193 ± 266, 2235 ± 881, 2489 ± 293, 2450 ± 130, 2585 ± 609, 3710 ± 200 years ago. These evidences are crucial in reconstructing paleo extreme wave events and will pave the way for regional correlation of erosional horizons along the northern margin of Indian Ocean

Development of Long-Term Aging Protocol for Implementation of the Illinois Flexibility Index Test (I-FIT)

The objective of this study was to evaluate long-term aging effects on asphalt mixtures using the Illinois Flexibility Index Test (I-FIT) and to develop a corresponding long-term aging protocol. The study recommended the use of the forced-draft oven as the aging equipment because of its availability, feasibility, practicability, capacity, and acceptable variability. A fully prepared semi-circular I-FIT specimen was chosen as the state of material during aging because it is practical, has limited operational variability, and its integrity is maintained during aging. The aging of compacted specimens for three days at 203°F (95°C) was found to be similar to aging for five days at 185°F (85°C) according to AASHTO R30, which is believed to be able to simulate up to 10 years of field aging. Hence, the 3D/95C aging method was chosen as the key component of the long-term aging protocol. Based on statistical analysis and oven-aging specimens immersed in argon, it was shown that the trends of aging after 1D/95C were similar to that observed after 3D/95C and 5D/85C. Hence, 1D/95C may be used as an indicator of 3D/95C aging for quality control purposes. Aging protocols were developed for laboratory-produced laboratory-compacted (LPLC) and plant-produced laboratory-compacted (PPLC) specimens. For LPLC, I-FIT on unaged and 3D/95C aged specimens should be conducted in all cases. A specific mix must have a mean flexibly index (FI) of unaged and 3D/95C aged specimens greater than 8.0 and 5.0, respectively, to be accepted. For PPLC, I-FIT procedure should be conducted on both unaged and 3D/95C aged specimens in all cases, while 1D/95C may be used by contractors to screen problematic mixes. Flexibility index higher than 8.0 and 4.0 for unaged and 3D/95C aged specimens, respectively, must be satisfied.IDOT-R27-175Ope

Haemoglobin level at birth is associated with short term outcomes and mortality in preterm infants

Background Blood volume and haemoglobin (Hb) levels are increased by delayed umbilical cord clamping, which has been reported to improve clinical outcomes of preterm infants. The objective was to determine whether Hb level at birth was associated with short term outcomes in preterm infants born at ≤32 weeks gestation. Methods Data were collected retrospectively from electronic records: Standardised Electronic Neonatal Database, Electronic Patient Record, Pathology (WinPath), and Blood Bank Electronic Database. The study was conducted in a tertiary perinatal centre with around 5,500 deliveries and a neonatal unit admission of 750 infants per year. All inborn preterm infants of 23 to 32 weeks gestational age (GA) admitted to the neonatal unit from January 2006 to September 2012 were included. The primary outcomes were intra-ventricular haemorrhage, necrotising entero-colitis, broncho-pulmonary dysplasia, retinopathy of prematurity, and death before discharge. The secondary outcomes were receiving blood transfusion and length of intensive care and neonatal unit days. The association between Hb level (g/dL) at birth and outcomes was analysed by multiple logistic regression adjusting for GA and birth weight (BWt). Results Overall, 920 infants were eligible; 28 were excluded because of missing data and 2 for lethal congenital malformation. The mean (SD) GA was 28.3 (2.7) weeks, BWt was 1,140 (414) g, and Hb level at birth was 15.8 (2.6) g/dL. Hb level at birth was significantly associated with all primary outcomes studied (P <0.001) in univariate analyses. Once GA and BWt were adjusted for, only death before discharge remained statistically significant; the OR of death for infants with Hb level at birth <12 g/dL compared with those with Hb level at birth of ≥18 g/dL was 4.1 (95% CI, 1.4–11.6). Hb level at birth was also significantly associated with blood transfusion received (P <0.01) but not with duration of intensive care or neonatal unit days. Conclusions Low Hb level at birth was significantly associated with mortality and receiving blood transfusion in preterm infants born at ≤32 weeks gestation. Further studies are needed to determine the association between Hb level at birth and long-term neurodevelopmental outcomes

Photocatalytic Nanolithography of Self-Assembled Monolayers and Proteins

Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon dioxide have been patterned photocatalytically on sub-100 nm length-scales using both apertured near-field and apertureless methods. Apertured lithography was carried out by means of an argon ion laser (364 nm) coupled to cantilever-type near-field probes with a thin film of titania deposited over the aperture. Apertureless lithography was carried out with a helium–cadmium laser (325 nm) to excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This latter approach is readily implementable on any commercial AFM system. Photodegradation occurred in both cases through the localized photocatalytic degradation of the monolayer. For alkanethiols, degradation of one thiol exposed the bare substrate, enabling refunctionalization of the bare gold by a second, contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule provided a facile means for protein patterning. Lines were written in a protein-resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive, aldehyde-functionalized regions. These were derivatized with aminobutylnitrilotriacetic acid, and complexed with Ni2+, enabling the binding of histidine-labeled green fluorescent protein, which yielded bright fluorescence from 70-nm-wide lines that could be imaged clearly in a confocal microscope