Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma

© 2020 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd A simple, sensitive and cost-effective HPLC-UV bioanalytical method for determination of lopinavir (LPV) in rat and human plasma was developed and validated. The plasma sample preparation procedure includes a combination of protein precipitation using cold acetonitrile and liquid–liquid extraction with n-hexane–ethyl acetate (7:3, v/v). A good chromatographic separation was achieved with a Phenomenex Gemini column (C18, 150 mm × 2.0 mm, 5 μm) at 40°C with gradient elution, at 211 nm. Calibration curves were linear in the range 10–10,000 ng/mL, with a lower limit of quantification of 10 ng/mL using 100 μL of plasma. The accuracy and precision in all validation experiments were within the criteria range set by the guidelines of the Food and Drug Administration. This method was successfully applied to a preliminary pharmacokinetic study in rats following an intravenous bolus administration of LPV. Moreover, the method was subsequently fully validated for human plasma, allowing its use in therapeutic drug monitoring (TDM). In conclusion, this novel, simple and cost-efficient bioanalytical method for determination of LPV is useful for pharmacokinetic and drug delivery studies in rats, as well as TDM in human patients

Effect of some biotic factors on microbially-induced calcite precipitation in cement mortar

Sporosarcina pasteurii, a common soil bacterium has been tested for microbial treatment of cement mortar. The present study also seeks to investigate the effects of growth medium, bacterial concentration and different buffers concerning the preparation of bacterial suspensions on the compressive strength of cement mortar. Two growth media, six different suspensions and two bacterial concentrations were used in the study. The influence of growth medium on calcification efficiency of S. pasteurii was insignificant. Significant improvement in the compressive as well as the tensile strength of cement mortar was observed. Microbial mineral precipitation visualized by Scanning Electron Microscopy (SEM) shows fibrous material that increased the strength of cement mortar. Formation of thin strands of fillers observed through SEM micrographs improves the pore structure, impermeability and thus the compressive as well as the tensile strengths of the cement mortar. The type of substrate and its molarity have a significant influence on the strength of cement mortar

Rock fracture grouting with microbially induced carbonate precipitation

Microbially induced carbonate precipitation has been proposed for soil stabilization, soil strengthening and permeability reduction as an alternative to traditional cement and chemical grouts. In this paper we evaluate the grouting of fine aperture rock fractures with calcium carbonate, precipitated through urea hydrolysis, by the bacteria Sporosarcina pasteurii. Calcium carbonate was precipitated within a small-scale and a near field-scale (3.1 m2) artificial fracture consisting of a rough rock lower surfaces and clear polycarbonate upper surfaces. The spatial distribution of the calcium carbonate precipitation was imaged using time-lapse photography and the influence on flow pathways revealed from tracer transport imaging. In the large-scale experiment, hydraulic aperture was reduced from 276 μm to 22 μm, corresponding to a transmissivity reduction of 1.71x10-5 m2/s to 8.75x10-9 m2/s, over a period of 12 days under constantly flowing conditions. With a modified injection strategy a similar three orders of magnitude reduction in transmissivity was achieved over a period of three days. Calcium carbonate precipitated over the entire artificial fracture with strong adhesion to both upper and lower surfaces and precipitation was controlled to prevent clogging of the injection well by manipulating the injection fluid velocity. These experiments demonstrate that microbially induced carbonate precipitation can successfully be used to grout a fracture under constantly flowing conditions and may be a viable alternative to cement based grouts when a high level of hydraulic sealing is required and chemical grouts when a more durable grout is required

Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol

© 2021 Elsevier B.V. Lipid-based formulations play a significant role in oral delivery of lipophilic drugs. Previous studies have shown that natural sesame oil promotes the intestinal lymphatic transport and oral bioavailability of the highly lipophilic drug cannabidiol (CBD). However, both lymphatic transport and systemic bioavailability were also associated with considerable variability. The aim of this study was to test the hypothesis that pre-digested lipid formulations (oleic acid, linoleic acid, oleic acid with 2-oleoylglycerol, oleic acid with 2-oleoylglycerol and oleic acid with glycerol) could reduce variability and increase the extent of the intestinal lymphatic transport and oral bioavailability of CBD. The in vivo studies in rats showed that pre-digested or purified triglyceride did not improve the lymphatic transport and bioavailability of CBD in comparison to sesame oil. Moreover, the results suggest that both the absorption of lipids and the absorption of co-administered CBD were more efficient following administration of natural sesame oil vehicle compared with pre-digested lipids or purified trioleate. Although multiple small molecule constituents and unique fatty acid compositions could potentially contribute to a better performance of sesame oil in oral absorption of lipids or CBD, further investigation will be needed to identify the mechanisms involved

Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes

The introduction of combination antiretroviral therapy (cART) led to substantial improvement in mortality and morbidity of HIV-1 infection. However, the poor penetration of antiretroviral agents to HIV-1 reservoirs limit the ability of the antiretroviral agents to eliminate the virus. Mesenteric lymph nodes (MLNs) are one of the main HIV-1 reservoirs in patients under suppressive cART. Intestinal lymphatic absorption pathway substantially increases the concentration of lipophilic drugs in mesenteric lymph and MLNs when they are co-administered with long-chain triglyceride (LCT). Chylomicrons (CM) play a crucial role in the intestinal lymphatic absorption as they transport drugs to the lymph lacteals rather than blood capillary by forming CM-drug complexes in the enterocytes. Thus, lipophilic antiretroviral drugs could potentially be delivered to HIV-1 reservoirs in MLNs by LCT-based formulation approach. In this study, protease inhibitors (PIs) were initially screened for their potential for intestinal lymphatic targeting using a computational model. The candidates were further assessed for their experimental affinity to CM. Tipranavir (TPV) was the only-candidate with substantial affinity to both artificial and natural CM in vitro and ex vivo. Pharmacokinetics and biodistribution studies were then performed to evaluate the oral bioavailability and intestinal lymphatic targeting of TPV in rats. The results showed similar oral bioavailability of TPV with and without co-administration of LCT vehicle. Although LCT-based formulation led to 3-fold higher concentrations of TPV in mesenteric lymph compared to plasma, the levels of the drug in MLNs were similar to plasma in both LCT-based and lipid-free formulation groups. Thus, LCT-based formulation approach alone was not sufficient for effective delivery of TPV to MLNs. Future efforts should be directed to a combined highly lipophilic prodrugs/lipid-based formulation approach to target TPV, other PIs and potentially other classes of antiretroviral agents to viral reservoirs within the mesenteric lymphatic system

Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol

Although natural sesame oil has been shown to facilitate the lymphatic delivery and oral bioavailability of the highly lipophilic drug cannabidiol (CBD), considerable variability remains an unresolved challenge. Vegetable oils differ substantially in composition, which could lead to differences in promotion of intestinal lymphatic transport of lipophilic drugs. Therefore, the differences in composition of sesame, sunflower, peanut, soybean, olive and coconut oils and their corresponding role as vehicles in promoting CBD lymphatic targeting and bioavailability were investigated in this study. The comparative analysis suggests that the fatty acids profile of vegetable oils is overall similar to the fatty acids profile in the corresponding chylomicrons in rat lymph. However, arachidonic acid (C20:4), was introduced to chylomicrons from endogenous nondietary sources. Overall, fatty acid composition of natural vegetable oils vehicles affected the intestinal lymphatic transport and bioavailability of CBD following oral administration in this work. Olive oil led to the highest concentration of CBD in the lymphatic system and in the systemic circulation in comparison to the other natural vegetable oils following oral administration in rats

Hydrodynamic coupling in microbially mediated fracture mineralization : formation of self-organized groundwater flow channels

Evidence of fossilized microorganisms embedded within mineral veins and mineral-filled fractures has been observed in a wide range of geological environments. Microorganisms can act as sites for mineral nucleation and also contribute to mineral precipitation by inducing local geochemical changes. In this study, we explore fundamental controls on microbially induced mineralization in rock fractures. Specifically, we systematically investigate the influence of hydrodynamics (velocity, flow rate, aperture) on microbially mediated calcite precipitation. Our experimental results demonstrate that a feedback mechanism exists between the gradual reduction in fracture aperture due to precipitation, and its effect on the local fluid velocity. This feedback results in mineral fill distributions that focus flow into a small number of self-organizing channels that remain open, ultimately controlling the final aperture profile that governs flow within the fracture. This hydrodynamic coupling can explain field observations of discrete groundwater flow channeling within fracture-fill mineral geometries where strong evidence of microbial activity is reported

Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach

© 2020 Elsevier B.V. The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing the size of HIV reservoirs within the mesenteric lymphatic system

Life-long Programming Implications of Exposure to Tobacco Smoking and Nicotine Before and Soon After Birth: Evidence for Altered Lung Development

Tobacco smoking during pregnancy remains common, especially in indigenous communities, and likely contributes to respiratory illness in exposed offspring. It is now well established that components of tobacco smoke, notably nicotine, can affect multiple organs in the fetus and newborn, potentially with life-long consequences. Recent studies have shown that nicotine can permanently affect the developing lung such that its final structure and function are adversely affected; these changes can increase the risk of respiratory illness and accelerate the decline in lung function with age. In this review we discuss the impact of maternal smoking on the lungs and consider the evidence that smoking can have life-long, programming consequences for exposed offspring. Exposure to maternal tobacco smoking and nicotine intake during pregnancy and lactation changes the genetic program that controls the development and aging of the lungs of the offspring. Changes in the conducting airways and alveoli reduce lung function in exposed offspring, rendering the lungs more susceptible to obstructive lung disease and accelerating lung aging. Although it is generally accepted that prevention of maternal smoking during pregnancy and lactation is essential, current knowledge of the effects of nicotine on lung development does not support the use of nicotine replacement therapy in this group

Application of calcifying bacteria for remediation of stones and cultural heritages

Since ages, architects and artists worldwide have focused on usage of durable stones as marble and limestone for construction of beautiful and magnificent historic monuments as European Cathedrals, Roman, and Greek temples, Taj Mahal etc. But survival of these irreplaceable cultural and historical assets is in question these days due to their degradation and deterioration caused by number of biotic and abiotic factors. These causative agents have affected not only the esthetic appearance of these structures, but also lead to deterioration of their strength and durability. The present review emphasizes about different causative agents leading to deterioration and application of microbially induced calcium carbonate precipitation as a novel and potential technology for dealing with these problems. The study also sheds light on benefits of microbial carbonate binders over the traditional agents and future directions