Serum levels of vasoactive factors in HIV-infected pre-eclamptic women on HAART.

In South Africa, pre-eclampsia (PE) and human immunodeficiency virus (HIV) infection are major causes of pregnancy-related deaths. This study aimed to measure serum levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) in HIV-infected highly active antiretroviral therapy (HAART)-treated and HIV-uninfected PE and normotensive women to ascertain if HIV/HAART alters their concentrations. Mean sFlt-1 levels were significantly up-regulated in the PE (HIV-uninfected 4.39 ± 1.29; HIV-infected 5.10 ± 1.10 ng/ml) compared to normotensive women (HIV-uninfected 2.59 ± 0.83; HIV-infected 2.20 ± 0.85 ng/ml). Mean PlGF levels were significantly lower in HIV-uninfected PE vs. HIV-infected normotensive women (29.69 ± 4.47 pg/ml vs. 32.86 ± 6.46 pg/ml; p = .002). In conclusion, PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels. Infection with HIV may have further increased the sFlt-1 levels.IMPACT STATEMENTWhat is already known on this subject? In PE, the numerous identified local and circulating bioactive factors differed in concentrations when compared to normal pregnancy.What do the results of this study add? PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels as well as increased levels of sFlt-1.What are the implications of these findings for clinical practice and/or further research? Understanding the link between PE, HIV and HAART during pregnancy will improve prognosis, management and treatment strategies for women clinically.

Liposomes with pH responsive 'on and off' switches for targeted and intracellular delivery of antibiotics.

pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with 'On' and 'Off'' pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.4. The QL-liposomes had a negative zeta potential at pH 7.4 that switched to a positive charge at acidic pH. VCM release from the liposome was quicker at pH 6 than pH 7.4. The OA-QL-liposome showed 4-fold lower MIC at pH 7.4 and 8- and 16-fold lower at pH 6.0 against both MSSA and MRSA compared to the bare drug. OA-QL liposome had a 1266.67- and 704.33-fold reduction in the intracellular infection for TPH-1 macrophage and HEK293 cells respectively. In vivo studies showed that the amount of MRSA recovered from mice treated with formulations was 189.67 and 6.33-fold lower than the untreated and bare VCM treated mice respectively. MD simulation of the QL lipid with the phosphatidylcholine membrane (POPC) showed spontaneous binding of the lipid to the bilayer membrane both electrostatic and Van der Waals interactions contributed to the binding. These studies demonstrated that the 'On' and 'Off' pH responsive liposomes enhanced the activity targeted and intracellular delivery VCM.

Phytochemical constituents and in vitro anticancer screening of isolated compounds from Eriocephalus africanus‡.

This study investigated the in vitro anticancer potential of phytochemical constituents isolated from the methanolic extract of Eriocephalus africanus. One flavanone (hesperidin) and two flavones (luteolin and apigenin) were isolated for the first time from the plant using column chromatography. Standard MTT assay was used to evaluate the effect of the constituents on cell viability in MCF-7, A549, HepG2 and normal HEK 293 cell lines. The flavonoids decreased cell viability in a dose dependent manner in all tested cell lines. Hesperidin and luteolin were more sensitive against MCF-7, with EC50 values of 62.57 µg/mL and 70.34 µg/mL, respectively and apigenin showed the most potent activity against HepG2 (EC50 = 11.93 µg/mL). The results revealed E. africanus to be a rich source of flavonoids and natural anticancer agents, which could potentially be used in the development of new therapeutics for cancer treatment.

Metal Nanoparticles: a Promising Treatment for Viral and Arboviral Infections.

Globally, viral diseases continue to pose a significant threat to public health. Recent outbreaks, such as influenza, coronavirus, Ebola, and dengue, have emphasized the urgent need for new antiviral therapeutics. Considerable efforts have focused on developing metal nanoparticles for the treatment of several pathogenic viruses. As a result of these efforts, metal nanoparticles are demonstrating promising antiviral activity against pathogenic surrogates and clinical isolates. This review summarizes the application of metal nanoparticles for the treatment of viral infections. It provides information on synthesis methods, size-related properties, nano-bio-interaction, and immunological effects of metal nanoparticles. This article also addresses critical criteria and considerations for developing clinically translatable nanosized metal particles to treat viral diseases.

pH-Responsive Lipid-Dendrimer Hybrid Nanoparticles: An Approach To Target and Eliminate Intracellular Pathogens.

pH-responsive drug delivery systems are yielding opportunities to directly deliver antibiotics to the site of infection. Therefore, this study aimed to develop and evaluate novel pH-responsive lipid-dendrimer hybrid nanoparticles (LDH-NPs) for the delivery of vancomycin (VCM) to the site of infection, by intracellular bacterial pathogens. The LDH-NPs were formulated using the emulsification solvent evaporation method and were characterized by various in vitro and molecular dynamic (MD) simulation techniques. LDH-NPs were 124.4 ± 2.01 nm in size, with a zeta-potential of -7.15 ± 2.98 mV and drug entrapment efficiency of 82.70 ± 4.09%, which exhibited pH-responsive behavior by shifting the surface charge from negative at physiological pH to positive in acidic pHs, with a size increase from 124.4 ± 2.01 to 173.9 ± 13.38 nm, and 252.7 ± 3.98 nm at pHs of 7.4, 6.0, and 4.5, respectively. Results indicated that the in vitro drug release of VCM from LDH-NPs occurred faster at pH 6.0 than at pH 7.4. The antibacterial activity of LDH-NPs against methicillin-resistance Staphylococcus aureus (MRSA) showed 8-fold lower MICs at pH 6.0 and 7.4, compared to treatment with VCM only. A bacterial cell viability study showed LDH-NPs had an 84.19% killing of MRSA, compared to VCM (49.26%) at the same MIC, further confirming its efficacy. Cell uptake studies showed that LDH-NPs intracellularly accumulated in HEK 293 cells, confirming significant clearance (p < 0.0001) of intracellular bacteria. MD simulation showed that interaction between the dendrimer and oleylamine was predominantly governed by van der Waals (VdW) interactions; whereas the interaction between the dendrimer and VCM was governed by both VdW and electrostatic interactions. Therefore, this study concludes that the pH-responsive release of VCM enhanced antibacterial efficacy against MRSA and intracellular delivery of an antibiotic. Thus, LDH-NPs is a promising nanocarrier system for antibiotics with the potential to improve the treatment outcomes of bacterial infections in patients with antibiotic resistant strains.

Synthesis of phthalocyanine conjugates with gold nanoparticles and liposomes for photodynamic therapy.

The efficiency of [2,9,17,23-tetrakis-(1,6-hexanedithiol)phthalocyaninato]zinc(II) as a photodynamic therapy (PDT) agent was investigated. This compound belongs to the second generation of photosensitizers currently tested for the cellular photo-damage of cancer cells. The production of reactive oxygen species (ROS) and phototoxicity of the photosensitizer were assessed. Healthy fibroblast cells and breast cancer (MCF-7) cells were treated with either free phthalocyanine or phthalocyanine bound to either gold nanoparticles or encapsulated in liposomes. Cell viability studies showed the optimum phototoxic effect on non-malignant cells to be 4.5 J cm(-2). The PDT effect of the liposome bound phthalocyanine showed extensive damage of the breast cancer cells. Gold nanoparticles only showed a modest improvement in PDT activity.