Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation’s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug’s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

A Composite Ranking of Risk Factors for COVID-19 Time-To-Event Data from a Turkish Cohort

Having a complete and reliable list of risk factors from routine laboratory blood test for COVID-19 disease severity and mortality is important for patient care and hospital management. It is common to use meta-analysis to combine analysis results from different studies to make it more reproducible. In this paper, we propose to run multiple analyses on the same set of data to produce a more robust list of risk factors. With our time-to-event survival data, the standard survival analysis were extended in three directions. The first is to extend from tests and corresponding p-values to machine learning and their prediction performance. The second is to extend from single-variable to multiple-variable analysis. The third is to expand from analyzing time-to-decease data with death as the event of interest to analyzing time-to-hospital-release data to treat early recover as a meaningful event as well. Our extension of the type of analyses leads to ten ranking lists. We conclude that 20 out of 30 factors are deemed to be reliably associated to faster-death or faster-recovery. Considering correlation among factors and evidenced by stepwise variable selection in random survival forest, 10~15 factors seem to be able to achieve the optimal prognosis performance. Our final list of risk factors contains calcium, white blood cell and neutrophils count, urea and creatine, d-dimer, red cell distribution widths, age, ferritin, glucose, lactate dehydrogenase, lymphocyte, basophils, anemia related factors (hemoglobin, hematocrit, mean corpuscular hemoglobin concentration), sodium, potassium, eosinophils, and aspartate aminotransferase.

Improvement in Emotion Regulation While Detained Predicts Lower Juvenile Recidivism

The goal of the current study was to investigate the relationships between observer-rated skills related to emotional and cognitive regulation post-admission and pre-release in a secure facility and official records of juvenile felony recidivism up to 1 year after release. Data came from a sample of 599 youth in a residential facility in Washington state (84% male; 38% White). Latent change score models indicated that both initial level of emotional regulation skills and improvement in emotion regulation skills while incarcerated were significantly related to lower recidivism. This pattern of findings remained when controlling for length of stay, among other covariates. Follow-up analyses indicated that the results for emotion regulation skills might be driven primarily by monitoring internal and external triggers. Additional research should investigate the connection between emotion regulation skills and juvenile recidivism, with a special focus on trigger monitoring and how to improve those skills.

Short-term retention in metallic PFCs: modelling in view of mass spectrometry and LIBS

Based on the conventional model of hydrogen retention in plasma-facing components, the question of hydrogen outgassing during and after plasma exposure is addressed in relation to mass spectrometry and laser-induced breakdown sprectroscopy (LIBS) measurements. Fundamental differences in retention and release data acquired by LIBS and by mass spectrometry are described analytically and by modelling. Reaction-diffusion simulations are presented that demonstrate possible thermal outgassing effects caused by LIBS. Advantages and limitations of LIBS as a tool for analysis of short term retention are discussed.

Could Government Data Openness Enhance Urban Innovation Capability? An Evaluation Based on Multistage DID Method

The wave of government data opening has gradually swept the world since it rose from the United States in 2009. The purpose is not to open government data, but to release data value and drive economic and social development through data accessibility. At present, the impact of academic circles on government open data mostly stays in theoretical discussion, especially due to the lack of empirical tests. Using the multistage difference-in-difference (DID) model, this paper analyzes the panel data from 2009 to 2016 by taking two batches of Chinese cities with open data released in 2014 and 2105 as samples to test the impact of government data opening on urban innovation ability. The results show that the opening of government data significantly improves urban innovation abilities. After considering the heterogeneity and fixed effects of urban characteristics, the opening of government data still significantly improves urban innovation ability and shows a greater innovation driving role in cities with high levels of economic development, human capital, and infrastructure. Based on this, this paper believes that we should continue to promote the opening of government data, release the value of data, and pay attention to the Matthew effect between cities that may appear in the era of big data.

Preparation, characterization, and in vitro release kinetics of doxorubicin-loaded magnetosomes

The doxorubicin (DOX) was successfully coupled to the magnetosomes from Acidithiobacillus ferrooxidans ( At. ferrooxidans) by genipin bridging. The parameters (magnetosome concentration, DOX concentration, genipin concentration-, and cross-link time) expected for temperature significantly influenced the coupling rate. Bacterial magnetosome-doxorubicin complexes (BMDCs) were characterized by transmission electron microscope (TEM), particle size analyzer and Fourier transform infrared spectroscopy. Results indicated that BMDCs exhibited a mean particle size of 83.98 mm and displayed a negative charge. The chemical reaction occurring between CO and NH group and the physical adsorption predominated by electrostatic interaction were found to involve in coupling. BMDCs can release 40% of DOX in simulated gastrointestinal conditions within 38 h. Kinetic models including Higuchi, Korsmeyer–Peppas, Zero order, First order, Hixon-Crowell, Baker-Lonsdale, and Weibull and Gompertz were utilized to explore the release mechanism of DOX from BMDCs. All models were found to fit well (r2 ≥ 0.8144) with the release data and the Gompertz was the best fit model (r2 = 0.9742), implying that the complex mechanisms involving Fickian and Gompertz diffusion contributed to the release. These findings suggested that magnetosomes from At. ferrooxidans have great potential applications in biomedical and clinical fields as the carrier of target drug delivery systems in the future.

Aliphatic Polyester Nanoparticles for Drug Delivery Systems

Drug delivery systems using aliphatic polyester nanoparticles are usually prepared via an emulsion process. These nanoparticles can control drug release and improve pharmacokinetics. Aliphatic polyesters are linear polymers containing ester linkages, showing sensitivity to hydrolytic degradation. The byproducts then promote autocatalytic degradation. These byproducts could enter the Krebs cycle and be eliminated from the body, resulting in the high biocompatibility of these nanoparticles. The properties of these polyesters are linked to the drug release rate due to biodegradation, i.e., polymer crystallinity, glass transition temperature, polymer hydrophobicity, and molecular weight (MW), all of which relatively influence hydrolysis. Mathematical equations have been used to study the factors and mechanisms that affect drug dissolution compared to experimental release data. The equations used as models for predicting the kinetics of drug release include the zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas equations. Aliphatic polyester-based controlled drug delivery has surrounded much of the current activity in the estimation parameters of nanoparticles and stimulated additional research. Polymeric nanoparticles have potential in a wide range of applications, such as in biotechnology, vaccine systems, and the pharmaceutical industry. The main goal of this chapter is to discuss aliphatic polyester nanoparticles as drug carrier systems.

Properties of Mosquito Repellent-Plasticized Poly(lactic acid) Strands

Poly(lactic acid) (PLA) is an attractive candidate for replacing petrochemical polymers because it is fully biodegradable. This study investigated the potential of PLA as a sustainable and environmentally friendly alternative material that can be developed into commercially viable wearable mosquito repellent devices with desirable characteristics. PLA strands containing DEET and IR3535 were prepared by twin screw extrusion compounding and simultaneously functioned as plasticizers for the polymer. The plasticizing effect was investigated by thermal and rheological studies. DSC studies showed that the addition of DEET and IR3535 into PLA strands reduced the glass transition temperature consistent with predictions of the Fox equation, thus proving their efficiency as plasticizers. The rheology of molten samples of neat PLA and PLA/repellents blends, evaluated at 200 °C, was consistent with shear-thinning pseudoplastic behaviour. Raman studies revealed a nonlinear concentration gradient for DEET in the PLA strand, indicating non-Fickian Type II transport controlling the desorption process. Release data obtained at 50 °C showed initial rapid release followed by a slower, near constant rate at longer times. The release rate data were fitted to a novel modification of the Peppas-Sahlin desorption model.

Formulation and Evaluation of Sustained Release Floating Pellets of Amlodipine Besylate

The aim of the present study is to design and develop sustained release pellets formulations for Amlodipine besylate. Amlodipine is an oral antihypertensive agent, commonly used as calcium channel blocker for treating high blood pressure. It is frequently used to treat heart diseases like angina pectoris. The dose of Amlodipine in case of hypertension or angina initially 5 mg daily later adjusted to 10 mg daily by oral route. Amlodipine has a maximum solubility in acidic pH. Amlodipine has a high bioavailability ranging from 60 to 80 % and slow rate of elimination. Amlodipine besylate at different drug to polymer ratios were prepared by extrusion and spheronization technique. The influence of the proportion of the polymer on the release rate of the drug from the pellets was studied. The in-vitro release studies of pellets were carried out in 0.1N HCl for 12 hours. The studies indicated that the drug release can be modulated by varying the concentration of the polymer. Pellets were prepared and evaluated for loose bulk density, tapped bulk density, compressibility index and angle of repose, shows satisfactory results. Formulation was optimized on the basis of acceptable pellet properties and in-vitro drug release. The resulting formulation produced robust pellets with acceptable drug content and low friability. The release data was fitted to various mathematical models such as, Higuchi, Korsmeyer- Peppas, First-order and Zero-order to evaluate the kinetics and mechanism of the drug release. Keywords: Sustained release, Ethyl cellulose, HPMC, Pellets, Amlodipine besylate

Formulation and Evaluation of Transdermal Patch of Apixaban

The aim of the present investigation was to develop and evaluate transdermal patch of Apixaban. Formulation development of Apixaban Transdermal patch was initiated using Eudragit S 100 and HPMC E50 LV as matrix controlling polymer for matrix type Transdermal Patch. PEG 400 was selected as plasticizer. Glycerin was selected as permeability enhancer. Preformulation study was performed to check the drug excipient compatibility. The IR spectra of Drug and final formulation found satisfactory. There are no any interaction between drug and excipients. Further the linearity curve was developed in UV for method of analysis. Trials A1-A14 was initiated using different concentration of polymers in the formulation. The prepared patches were transparent and smooth in surface. The weight variation was found well within acceptable range. The thickness of patches was found uniform in nature and the variation is found satisfactory. Further, the surface pH of the patches was found between 6.8 to 7.1 and it is acceptable. The drug content, folding endurance and %elongation results of A1-A14 batches were found well within acceptable range. Initially the trial batches were taken with a single polymer like HPMC and EudragitS100. The drug release was not achieved as per the target drug release profile for 8hours. Hence the combination of these two polymers are taken and found better results than the single polymers. Based on the drug release data, it was observed that the A8 batch was the most satisfactory batch with respect to drug release and other parameters. Hence, the A8 batch selected as optimized batch and Stability study of the same batch initiated.