Current Pharmaceutical Biotechnology - Volume 17, Issue 6, 2016

The cell-mediated immunity and cytotoxic agents play a significant role on tumor cell apoptosis. Tumor necrosis factor-α (TNF-α) is an intricate linker between inflammation and cancer through mediating the process of apoptosis and cell-mediated immunity. A variety of evidences have confirmed the critical role of TNF-α on tumor migration, proliferation, matrix degradation, tumor metastasis, invasion, and angiogenesis. Through binding to receptors, TNF-α participates in activating multiple cell signaling cascades that link inflammation, survival and evolution towards breast cancer. TNF-α is an important agent for tumor biotherapy, but its clinical application is limited for its severe fatal systemic toxicity. The poly-lactic acid microspheres (PLAM) with intratumoral cytokine release hold tremendous potential for the immunotherapy of breast cancer, and TNF-α antagonists may offer therapeutic potential in solid tumors. In addition, TNF-α is related with the blockage of estrogen and progesterone receptors. For breast cancer treatment, it is necessary to understand the molecular signaling pathways that mediate TNF-α and the aggressive behavior of negative breast cancer. The aim of present review is to summarize the effect of TNF-α on breast cancer cells.

Neurodegenerative diseases (NDs) caused by the progressive degeneration of brain neurons affect millions of people worldwide and pose significant public health challenges. Despite therapeutic advances in the treatment of these diseases, drug delivery to desired brain targets is difficult due to the intrinsic resistance of the blood-brain barrier (BBB). Many research groups are investigating novel strategies of transporting drug molecules across this barrier. Convection-enhanced delivery (CED) is a neurosurgical administration technique that has been recognized as an effective means of bypassing the BBB to deliver drugs to their clinical targets in pharmacologically relevant quantities. Currently, the drugs and devices being used in CED therapy remain at an investigational stage and have not been approved for use in actual treatment. This article provides a brief introduction of the etiologies of NDs, technical insights into CED and perspectives on the development and regulation of therapeutic products for the CED-based therapy of NDs.

Aristotelia chilensis ([Molina], Stuntz) a member of the family Eleocarpaceae, is a plant native to Chile that is distributed in tropical and temperate Asia, Australia, the Pacific Area, and South America. The juice of its berries has important medicinal properties, as an astringent, tonic, and antidiarrhoeal. Its many qualities make the maqui berry the undisputed sovereign of the family of so-called "superfruits", as well as a valuable tool to combat cellular inflammation of bones and joints. Recently, it is discovered that the leaves of the maqui berry have important antibacterial and antitumour activities. This review provides a comprehensive overview of the traditional use, phytochemistry, and biological activity of A. chilensis using information collected from scientific journals, books, and electronic searches. Anthocyanins, other flavonoids, alkaloids, cinnamic acid derivatives, benzoic acid derivatives, other bioactive molecules, and mineral elements are summarized. A broad range of activities of plant extracts and fractions are presented, including antioxidant activity, inhibition of visible light-induced damage of photoreceptor cells, inhibition of α-glucosidase, inhibition of pancreatic lipase, anti-diabetic effects, anti-inflammatory effects, analgesic effects, anti-diabetes, effective prevention of atherosclerosis, promotion of hair growth, anti-photo ageing of the skin, and inhibition of lipid peroxidation. Although some ethnobotanical uses have been supported in in vitro experiments, further studies of the individual compounds or chemical classes of compounds responsible for the pharmacological effects and the mechanisms of action are necessary. In addition, the toxicity and the side effects from the use of A. chilensis, as well as clinical trials, require attention.

Various nano-based strategies for increasing the efficiency of topical drugs have offered the potential advantage of miconazole skin delivery. Miconazole nitrate is an antifungal drug with a drawback of poor skin-penetration in the treatment of deep seated fungal skin infections. Drug entrapment in nanoparticles such as ethosome, liposomes, solid lipid nanoparticles (SLNs) and nano structured lipid carriers (NLCs) can facilitate localized drug delivery and remove the skin barriers for an efficient drug delivery. Different nano-formulations have been recently examined for the controlled release, retention and permeation enhancement of miconazole in skin. The present overview focuses on novel nano-based formulation approaches employed to improve miconazole penetration through skin for the treatment of fungal infections.

The conventional techniques used to extract natural products have many disadvantages, and alternative methods have been used, such as supercritical fluid extraction (SFE-CO2). We compared the anti-Mycobacterium tuberculosis activity and cytotoxicity of extracts and major pure compounds were obtained from the leaves of Calophyllum brasiliense by SFE-CO2, maceration and Soxhlet. Anti-M tuberculosis activity was evaluated by resazurin microtiter assay plate and cytotoxicity assay was performed using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide. The (-) mammea A/BB, (-) mammea B/BB, mammea B/BB cyclo D, ponnalide, mammea A/BA cyclo D, and amentoflavone were identified as the majority compounds. SFE-CO2, especially at 313 K and 10.92 MPa showed better yield for (-) mammea A/BB. Anti-M. tuberculosis activity (62.5 μg/mL) and cytotoxicity (Selectivity Index = 0.320-0.576) were similar for the three extracts. Mammea B/BB cyclo D had a minimum inhibitory concentration (MIC) of 125 μg/mL, and ponnalide and mammea A/BA cyclo D had MICs > 250 μg/mL. The pure compounds isolated showed low Selectivity Index (< 0.09). SFE-CO2 may be more promising than conventional methods for the extraction of compound (-) mammea A/BB, which presented the best anti-M. tuberculosis activity in our previous study. This is important for current industrial requirements to obtain extracts from medicinal plants using clean technologies.

Present exploration deals with the therapeutic perspective of methyl gallate isolated from the leaf extract of Acacia nilotica (L.) Delile in contrast to food-borne bacterial pathogen's viz., Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aeruginosa and Staphylococcus aureus with their evolutionary succession. The extract was subjected to phytochemical analysis and isolated compound was identified as methyl gallate using UV-vis, IR and NMR spectra. It was found most potent against K. pneumoniae with its minimum inhibition concentration (MIC) of 0.32 mg/ml and minimum bactericidal concentration (MBC) at 0.62 mg/ml. The correlation of MIC values with an evolutionary succession assists the relationship between their genetic and toxic properties. The cytotoxic pursuit of methyl gallate was additionally assessed over NIH3T3 mouse fibroblast by Neutral red (NR) uptake, MTT cell proliferation assay and did not disclose any relevant influence on cell viability as well as cell proliferation. As such, the methyl gallate extracted from the leaf of A. nilotica holds massive antibacterial aptitude and hands out towards a new paradigm for food and pharmaceutical industries.

Context: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. Methods: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. Results and discussion: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC0-∞ following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. Conclusion: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Background: Optimal skin repair has been a desired goal for many researchers. Recently, plasma rich in growth factors (PRGF) has gained importance in dermatology proving it is beneficial effects in wound healing and cutaneous regeneration. Objective: The anti-fibrotic, pro-contractile and photo-protective effect of PRGF on dermal fibroblasts and 3D skin models has been evaluated. Method: The effect against TGFβ1 induced myofibroblast differentiation was tested. Cell contractile activity over collagen gel matrices was analyzed and the effect against UV derived photo-oxidative stress was assessed. The effectiveness of PRGF obtained from young aged and middle aged donors was compared. Furthermore, 3D organotypic skin explants were used as human skin models with the aim of analyzing ex vivo cutaneous preventive and regenerative photo-protection after UV exposure. Results: TGFβ1 induced myofibroblast levels decreased significantly after treatment with PRGF while the contractile activity increased compared to the control group. After UV irradiation, cell survival was promoted while apoptotic and ROS levels were noticeably reduced. Photo-exposed 3D explants showed higher levels of metabolic activity and lower levels of necrosis, cell damage, irritation and ROS formation when treated with PRGF. The histological integrity and connective tissue fibers showed lower signals of photodamage among PRGF injected skin models. No significant differences for the assessed biological outcomes were observed when PRGF obtained from young aged and middle aged donors were compared. Conclusion: These findings suggest that this autologous approach might be useful for antifibrotic wound healing and provide an effective protection against sun derived photo-oxidative stress regardless the age of the patient.