Abstract
Designing and synthesizing biodegradable drug delivery systems are key research areas in biomedical nanotechnology. Here, we report the development of biodegradable magnesium-layered ...hydroxide (MgLH) based nanodelivery systems using magnesium oxide (MgO) as the precursor by a precipitation method. The designed nanocarrier does not contain any trivalent metal ions, which are most commonly used for the synthesis of layered double hydroxides (LDHs). The designed delivery system was characterized in detail using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and inductively coupled plasma (ICP) analyses. The anti-tuberculosis (anti-TB) drug pyrazinamide (PZA) was successfully intercalated into interlayer galleries of MgLH, resulting in the formation of the nanocomposite, PZA-MgLH, having an average size of about 107 ± 24 nm with a uniform circular shape. The in vitro release of PZA in a human body simulated phosphate buffer saline (PBS) solution was sustained (i.e., almost 66 h) and followed a pseudo-secondorder kinetic model. Moreover, the designed nanodelivery system was found to be highly biocompatible with human normal lung cells (MRC-5) and with 3T3 fibroblast cells as controls for 24 and 48 h. Lastly, the PZA-MgLH nanocomposite showed good anti-tuberculosis activity against
Mycobacterium tuberculosis
and both the PZA-MgLH nanocomposite and its released free drug PZA showed antibacterial activity against tested Gram-positive and Gram-negative bacteria with percentage inhibition ranging from 5.6% to 68% against
S. aureus, E. coli
, and
P. aeruginosa
for the PZA free drug, and 32% to 32.5% against
E. coli
for the PZA-MgLH nanocomposite. In summary, the present results provide significant evidence that the designed nanodelivery system can be used for the delivery of PZA and, thus, should be investigated further for a wide range of anti-TB applications.
Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, ...lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.
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The extraction efficiency of metals is improved by modified cloud point extraction (m-CPE) as compared to conventional approach (c⿿CPE).The preconcentration and enhancement factors ...obtained by m-CPE were 25⿿56% increased as compared to c-CPE.The elimination of surfactant effects via aqueous media, proposed by m-CPE, boosts up the selectivity of method.The analytes in aqueous media is well-matched with the conditions of atomic absorption spectrometry.
A new method based on modification of cloud point extraction for simultaneous enrichment of cadmium, lead and copper in water and fish muscle samples was proposed. The extraction efficiency by modified cloud point extraction (m-CPE) was compared with conventional cloud point extraction (c-CPE) method. The procedure for both CPE methods was comprised of formation of metal complexes with a hydrophobic chelating agent, dithizone, followed by entrapment of the chelates in a nonionic surfactant, Triton X-114. For c-CPE, the surfactant rich phase was treated with ethanolic solution of nitric acid and analyzed by flame atomic absorption spectrometer (FAAS). Whereas for m-CPE, aqueous nitric acid was used to back extract the metal ions from the surfactant rich phase and finally determined. The efficiency of the methods was tested by analyzing certified reference material and standard addition to a real sample. All the experimental parameters were optimized. At optimized experimental conditions, preconcentration and enhancement factors were 62.5 and 78.0 to 83.0 respectively for m-CPE, 25.0 and 56.0% higher than that of c-CPE. This improvement might be due to elimination of the effects of surfactant on the signal of analytes by FAAS. The developed method of m-CPE was applied successfully for analysis of the selected heavy metals in water and muscle tissues samples of fish of different lakes in Sindh, Pakistan.
An innovative, rapid, and simple dual-dispersive liquid-liquid microextraction (DDLL-ME) approach was used to extract uranium from real samples for the first time. The main objective of this study ...was to disperse extraction solvent by using an air-agitated syringe system to overcome matrix effects and avoid dispersion of hazardous dispersive organic solvents by using heat. The DDLL-ME method consisted of two dispersive liquid-liquid extraction steps with chloroform as the extracting solvent. Uranium formed complexes with 4-(2-thiazolylazo) resorcinol in the aqueous phase and was extracted in extracting solvent (chloroform) after the first dispersive liquid-liquid process. Uranium was then back-extracted in the acidic aqueous phase in a second dispersive liquid-liquid process. Finally, uranium was determined by a spectrophotometric detection technique. The variables that played a key role in the proposed method were studied and optimized. The LOD and sensitivity enhancement factor for uranium were found to be 0.60 µg/L and 45, respectively, under optimized conditions. Calibration graphs were found to be linear in the range of 5.0-600 µg/L. The RSD was 2.5%. Reliability of the proposed method was verified by analyzing certified reference material TM-28.3.
The abnormal metabolism of metal ions plays an important role in health and disease conditions; hence, the studies about them have received much interest. The objective of this study was to evaluate ...the association between trace and toxic elements zinc (Zn), cadmium (Cd), selenium (Se), and mercury (Hg) in biological samples (scalp hair, blood, and urine) of hypertensive patients (n = 257), residents of Hyderabad, Pakistan. For comparison purpose, the biological samples of age-matched healthy controls were selected as referents. The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials and by the conventional wet acid digestion method. The recovery of all studied elements was found in the range of 96.4–99.1 % in certified reference materials. The results of this study showed that the mean values of Cd and Hg were significantly higher in scalp hair, blood, and urine samples of hypertensive patients than in referents (P < 0.001), whilst the concentrations of Zn and Se were lower in the scalp hair and blood, but higher in the urine samples of hypertensive patients. The deficiency of Zn and Se and the high exposure of toxic metals may be synergistic with risk factors associated with hypertension.
In the present study, the environmental and occupational exposure of lead (Pb) has been assessed by analyzing the whole-blood samples of early adolescents (boys) aged 12-15 years working for the past ...1-3 years in battery recycling workshops (BRW). For comparative purpose, boys of the same age group residing in the vicinity of BRW (exposed non-workers) and who lived in domestic areas devoid of any industrial activity (referents boys) were selected. The blood samples were analyzed for Pb, along with biochemical parameters of blood. Both biological samples were oxidized by acid in a microwave oven before determination of Pb by graphite furnace atomic absorption spectrometry. The mean value of Pb concentration in blood samples of working boys was threefold higher as compared with referent boys. The significant negative correlations of blood Pb level with % Hb (r=-0.862) were observed in working boys.
The brown planthopper, Nilaparvata lugens, is a serious pest of rice crops throughout Asia and exhibits wing dimorphism, with brachypterous adults having reduced wings and macropterous adults ...possessing fully developed wings. To understand the reproductive strategies in two wing‐morphs of this insect, the transcript encoding the major yolk protein precursor, vitellogenin (Vg), was cloned. The complete mRNA transcript was 6314 bp, which encodes a protein of 2063 residues including an 18‐residue putative signal peptide. Analysis of the mature protein revealed two vitellogenin‐N (or lipoprotein amino‐terminal) domains near the N‐terminus and a von Willebrand factor type D domain near the C‐terminus. In addition, a highly conserved motif GL/ICG, and a number of cysteine residues were identified near the C‐terminus. Northern blot analysis identified a ∼6.8 kb Vg gene transcript that was expressed exclusively in the adult female fat body cells. The expression profile revealed that the Vg gene starts to be expressed earlier (on day 3) in brachypters as compared to macropters where the mRNA transcript was observed on day 4. However, in both morphs, the amount of Vg mRNA increased to reach high levels during vitellogenic periods from day 4 (in brachypters) and day 5 (in macropters) and onwards. Reflecting the RNA transcription pattern, the Vg signal was detected by immunoblotting on day 3 and day 4 in haemolymph of brachypterous and macropterous females, respectively, and that was increased every day and remained high during the vitellogenic periods. Furthermore, the topical application of juvenile hormone (JH) III had up‐regulated the Vg gene expression suggesting that the Vg gene is regulated by JH in N. lugens. In addition, it was demonstrated by Southern blot analysis that there exists a single copy of the gene in the N. lugens genome. A delayed trend in expression (of both the transcript and the protein) demonstrated by macropterous females in the present studies supports the hypothesis of prereproductive long distance migration in this wing‐dimorphic species.
Prenatal and early-life exposure to lead (Pb) is hypothesized to have adverse effects on childhood health. The aim of this study was to evaluate the prenatal exposure to Pb and its adverse effects on ...mothers and their infants who are residents of industrial (exposed) and domestic areas (referents) in Karachi, Pakistan. The biological samples (scalp hair and blood) of mother–infants pairs were analyzed for Pb levels by atomic absorption spectrometry after microwave-assisted acid digestion method. The Pb levels in scalp hair and blood samples of exposed mothers were found in the range of 7.52–8.70 μg/g and 115–270 μg/L, respectively, which were significantly higher than those values obtained for referent mothers (p < 0.001). The Pb levels in the blood (umbilical cord) and hair of neonates of exposed mother that were found in the range of 83–178 μg/L and 4.95–7.23 μg/g, respectively, were significantly higher than the obtained values of referent neonates (p > 0.001). The correlation between maternal and cord blood of both groups was found in the range of 0.708–0.724 (p < 0.01). It was observed that there were higher Pb burdens in exposed mothers and their infants as compared to referent mothers–neonates.
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