Current Pharmaceutical Biotechnology - Volume 20, Issue 7, 2019

Targeted drug delivery, also known as smart drug delivery or active drug delivery, is a subcategory of nanomedicine. Using this strategy, the medication is delivered into the infected organs in the patient’s body or to the targeted sites inside the cells. In order to improve therapeutic efficiency and pharmacokinetic characteristics of the active pharmaceutical agents, conjugation of biomacromolecules such as proteins, nucleic acids, monoclonal antibodies, aptamers, and nanoparticulate drug carriers, has been mostly recommended by scientists in the last decades. Several covalent conjugation pathways are used for biomacromolecules coupling with nanomaterials in nanomedicine including carbodiimides and “click” mediated reactions, thiol-mediated conjugation, and biotin-avidin interactions. However, choosing one or a combination of these methods with suitable coupling for application to advanced drug delivery is essential. This review focuses on new and high impacted published articles in the field of nanoparticles and biomacromolecules coupling studies, as well as their advantages and applications.

Background: Zinc oxide nanoparticles (ZnO NPs) are robustly used biomedicine. Moreover, no study has been conducted to explore the consequence of green synthesis of ZnO NPs with Camellia sinensis (green tea extract, GTE) on kidneys of rats treated with monosodium glutamate (MSG). Methods: Therefore, the objective of the research was designed to explore the possible defensive effect of GTE/ZnO NPs against MSG-induced renal stress investigated at redox and histopathological points. Results: The levels of urea and creatinine increased as the effect of a high dose of MSG, in addition, the myeloperoxidase and xanthine oxidase activates were elevated significantly with the high dose of MSG. The levels of non-enzymatic antioxidants (uric acid, glutathione, and thiol) were decreased sharply in MSG-treated rats as compared to the normal group. Conclusion: The data displayed that GTE/ZnO NPs reduced the effects of MSG significantly by reduction of the level peroxidation and enhancement intracellular antioxidant. These biochemical findings were supported by histopathology evaluation, which showed minor morphological changes in the kidneys of rats.

Background: Changes in expression of genes associated with proteins or organelles degradation system in the cell may be a cause or signal to carcinogenesis. Thus, the aim of this study was to assess the profile of gene expression linked to the degradation systems of proteins or organelles in histo-pathologically confirmed colorectal adenocarcinoma in relation to normal colon tissue. Methods: Using oligonucleotide microarrays and GeneSpring 13.0, and PANTHER 13.1 software’s we characterized 1095 mRNAs linked to the degradation system of proteins and organelles in sections of colorectal cancer from patients at various clinical stages of disease. Subsequent analyses with restrictive assumptions narrowed down the number of genes differentiating cancer, assuming a P-value of less than 0.05. Results: We found that most of the significant genes were silenced in the development of colorectal cancer. The FOXO1 had the lowest fold change value in the first clinical stage (CSI) comparing to the control. The HSPA8 was up-regulated in the two early clinical stages (CSI and CSII), and UBB only in the CSI. Only little-known PTPN22 showed increasing expression at all stages. Conclusion: In summary, the examined colorectal adenocarcinoma samples were characterized by almost complete silencing of the significant genes associated with the degradation of proteins and mitochondria in transcriptomic level. The FOXO1, HSPA8 and UBB genes may become potential diagnostic and/or therapeutic targets in the early stage of this cancer.

Background: Interferon-gamma release assays (IGRAs) are blood tests used to measure the amount of interferon-γ (IFN-γ) released by T lymphocytes after stimulation by antigens specific for the diagnosis of latent tuberculosis infection. A mitogen serves as a positive control to assess the immune function in IGRAs. Methods: This in vitro study was conducted to evaluate IFN-γ production by human whole blood stimulated with heat-treated and/or cation-supplemented phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), using QuantiFERON-TB Gold Kit ELISA tests. Results: The optimal concentrations of PWM, Con A and PHA for IGRAs were 2 μg/mL, 5 μg/mL and 10 μg/mL, respectively. The results showed that IFN-γ production in response to PWM was the highest and PHA was the lowest amount. The median values of three mitogens were in the following order: PWM≥Con A≥ positive control>>PHA-P>>negative control. PWM and PHA were heat stable, while Con A was heat sensitive. The mitogen response of lymphocytes to untreated or heat-treated PWM and heat-treated Con A was increased in 1 mM Ca2+-supplemented groups, whereas the response to heat-treated PHA was decreased. Exposure to 1 mM Mg2+ had no effect on untreated or heat-treated PWM, and a concentration of 1 mM Zn2+ inhibited the stimulation of un-treated PWM. We found that calcium supplementation improved the PWM-induced production of IFN-γ. Conclusion: Therefore, PWM is an appropriate mitogen for use as a positive control in IGRAs. It is a potential indicator of cytokine production in the diagnostic as well as research settings, and calcium supplementation improved stimulation.

Background: Eucalyptus belongs to the Myrtaceae family. It is the most planted hardwood forest crop worldwide, representing a global renewable resource of fiber, pharmaceuticals and energy. Objective: To compare the five species, E. maidenii, E. robusta, E. citriodora, E. tereticornis and E. camaldulensis, seeking for the richest source of nutrients and pharmaceuticals. Methodology: Eucalyptus samples were subjected to some chemical determinations for both primary and secondary metabolites to verify their nutritional and pharmaceutical importance related to different extracts. GC-MS analysis was applied to detect the presence of some individual phenolic constituents in their leaves. Results: E. robusta recorded the maximum contents of carbohydrates (40.07%) and protein (31.91%). While E. camaldulensis contained the highest contents of total phenolic compounds (46.56 mg/g), tannins (40.01 mg/g) and antioxidant activities assayed by the phosphomolybednum method (57.60 mg/g), followed by E. citridora. However, E. tereticornis exhibited the highest reducing power ability (151.23 mg/g). The GC-MS highlighted 20 phenolic constituents and antioxidants which varied in their abundance in Eucalyptus leaves, 8 individual phenolics (hydroquinone, hesperitin, pyrogallol, resorcinol, protocatechuic acid, naringenin, chlorogenic acid and catechin) were maximally recorded with E. camaldulensis and secondly, with E. citridora in case of at least 5 components. Nevertheless, gallic and quinic acids were more abundant in the leaves of E. tereticornis, which may explain its high corresponding reducing powers. Conclusion: Acetone-water combination has enhanced phenolics extraction from Eucalyptus tissues. This is the first report aiming to compare between the aforementioned Eucalyptus species highlighting either their nutritional or medicinal importance.

Objective: Korean red ginseng was reported to have many biological effects like the antioxidant and the anti-inflammatory activities. Oxidative stress and neuro-inflammation play major roles in the pathogenesis of Parkinson’s disease (PD). The current study aimed to investigate the protective effects of ginseng on rotenone-induced PD in rats. Methods: Rats were randomly allocated into 4 groups: normal rats, rotenone control, ginseng+rotenone and ginseng only treated rats. The severity of PD was evaluated through locomotor activity perceived in the open field test, histological examination and immunohistochemical detection of amyloid-β in brain tissues, in addition to the biochemical assessment of tyrosine hydroxylase activity in brain tissues. Moreover, the following parameters were investigated for studying the possible mechanisms of ginseng neuroprotective effect: nuclear factor-Κβ (NF-Κβ), tumor necrosis factor-alpha (TNF-α), caspase- 3, lipid peroxides and reduced glutathione (GSH). Results: Ginseng exhibited potent neuroprotective effect that was reflected upon the histopathological examination, marked improvement in the locomotor activity and through its ability to suppress the amyloid- β deposition in the cortex and striatum along with significant increase in the tyrosine hydroxylase activity. Ginseng successfully inhibited the NF-Κβ inflammatory pathway in brain tissues beside the inhibition of other oxidative stress and inflammatory mediators. Furthermore, it exhibited antiapoptotic effect via the inhibition of caspase-3 expression. Conclusion: Ginseng could be a promising treatment in PD. It can suppress dopaminergic neuron degeneration through variable mechanisms mainly via inhibition of NF-Κβ pathway in addition to inhibition of oxidative stress and apoptosis.

Background: Diabetes mellitus is the most common disease in Egypt. In this context, Beta vulgaris subspecies cicla L. var. flavescens is an edible plant that has been used in traditional medicine as a therapy for treating some diseases. Objectives: The current study was performed to evaluate the antibacterial and potential anti-diabetic activities of different extracts and isolated flavone C-glycoside compounds isolated from Beta vulgaris subspecies cicla L. var. flavescens leaves. Methods: Phytochemical investigation of n-butanol extract led to the isolation of five phytoconstituents. Their structures were determined by spectroscopic tools, including 1D-NMR (1H- & 13C-NMR) and 2D-NMR (HMQC & HMBC) besides the comparison of the data with the literature. The extracts and phytoconstituents were evaluated in vitro for their activity against some bacterial pathogens, which represent prominent human pathogens, particularly in hospital settings. The antibacterial activity was examined against three Gram-positive bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis & Enterococcus faecalis) and five Gram-negative ones (Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Proteus mirabilis & Salmonella typhimurium) relative to Ciprofloxacin as a reference drug. Furthermore, the in vitro antidiabetic activity (Type II) was evaluated using the alpha-glucosidase inhibitory assay. Results: Five flavone C-glycosides namely; Apigenin 8-C-β-D-glucopyranoside (vitexin) (1), 2''-Oxylopyranosylvitexin (2), acacetin 8-C-β-D-glucopyranoside (3), acacetin 8-C-α-L-rhamnoside (4), and 6,8-di-C-β-D-glucopyranosylapigenin (vecinin-II) (5) were isolated from n-butanol extract of B. vulgaris subspecies cicla L. var. flavescens. Compound 1 showed a promising antibacterial activity against most of the test bacterial strains with respect to the minimum inhibitory concentration values (MIC) ranged from 1.95 to 15.63 μg ml-1. On the other hand, compounds 1 and 3 demonstrated superior antidiabetic activities with IC50 values of 35.7 and 42.64 μg ml-1, respectively, while an inferior potential antidiabetic activity was recorded for compound 4 (IC50 = 145.5 μg ml-1) in comparison with Acarbose as a reference drug. Conclusion: B. vulgaris L. is an edible plant, which could be used as a natural source of antibiotic and hypoglycemic drugs.