Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell

Influence of mangiferin on membrane bound phosphatases and lysosomal hydrolases in streptozotocin induced diabetic rats

The activities of membrane-bound ATPases and lysosomal hydrolases are altered in tissues of streptozotocin (STZ)-induced diabetic rats. Diabetes is stimulating the deterioration of membrane function and weakens the intracellular metabolism. The objective of the present study was to determine the effect of mangiferin, isolated from Salacia chinensis on membrane bound phosphatases and lysosomal hydrolases in the liver and kidney of STZ-induced diabetic rats. In our investigation, the levels of blood glucose and glycosylated haemoglobin were significantly increased in the diabetic rats. Moreover, membrane bound phosphatases and lysosomal hydrolases activities were ominously altered in the liver and kidney of STZ-induced diabetic rats. The treatment of mangiferin (40 mg/kg body weight up to 30 days) significantly brought back the activities of enzymes to near normal, when compared to the experimentally induced diabetic rats. Based on this findings, mangiferin have a substantial outcome on membrane bound phosphatases and lysosomal hydrolases in diabetic condition.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Repeated infections of dengue (serotype DENV-2) in lung cells of BALB/c mice lead to severe histopathological consequences

To determine the effect of DENV (serotype 2) repeated infections on lung cells is the main goal of this study. From the result, lung histology of control BALB/c mice showed normal alveolar morphology, while vehicle control BALB/c mice highlighted a slight thickening of the alveolar septum. Lung histopathology of BALB/c mice infected twice by DENV-2 showed the presence of hemorrhage, plasma leakage and presence of hemosiderin-laden macrophages (HLMs). Notably, in the lung of BALB/c mice infected four times by DENV-2, we observed thickening and disruption of the alveolar septum, inflammatory cell infiltration, plasma leakage and increased cellularity. Megakaryocyte releasing platelets were also found into the lung alveolus. Overall, our findings showed severe histopathological damage in lungs repeatedly infected by DENV-2, allowing us to argue that they can be linked to pulmonary complication. Result also showed that the number of infections with similar total DENV-2 titer led to different histopathological changes

Synthesis of (cinnamate-zinc layered hydroxide) intercalation compound for sunscreen application

Background: Zinc layered hydroxide (ZLH) intercalated with cinnamate, an anionic form of cinnamic acid (CA), an efficient UVA and UVB absorber, have been synthesized by direct method using zinc oxide (ZnO) and cinnamic acid as the precursor. Results: The resulting obtained intercalation compound, ZCA, showed a basal spacing of 23.9 Å as a result of cinnamate intercalated in a bilayer arrangement between the interlayer spaces of ZLH with estimated percentage loading of cinnamate of about 40.4 % w/w. The UV–vis absorption spectrum of the intercalation compound showed excellent UVA and UVB absorption ability. Retention of cinnamate in ZLH interlayers was tested against media usually came across with sunscreen usage to show low release over an extended period of time. MTT assay of the intercalation compound on human dermal fibroblast (HDF) cells showed cytotoxicity of ZCA to be concentration dependent and is overall less toxic than its precursor, ZnO. Conclusions: (Cinnamate-zinc layered hydroxide) intercalation compound is suitable to be used as a safe and effective sunscreen with long UV protection effect

Identification of critical paralog groups with indispensable roles in the regulation of signaling flow

Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and ‘bowtieness’ when compared to other paralogs or other proteins in the signaling network. CPGs had higher diversity in all these measures, with more varied biological functions and more specific post-transcriptional regulation than non-critical paralog groups (non-CPG). Using TGF-beta, Notch and MAPK pathways as examples, SMAD2/3, NOTCH1/2/3 and MEK3/6-p38 CPGs were found to regulate the signaling flow of their respective pathways. Additionally, CPGs showed a higher mutation rate in both inherited diseases and cancer, and were enriched in drug targets. In conclusion, the results revealed two distinct types of paralog groups in the signaling network: CPGs and non-CPGs. Thus highlighting the importance of CPGs as compared to non-CPGs in drug discovery and disease pathogenesis

Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy

Despite the technological advancement in the biomedical science, cancer remains a life-threatening disease. In this study, we designed an anticancer nanodelivery system using graphene oxide (GO) as nanocarrier for an active anticancer agent gallic acid (GA). The successful formation nanocomposite (GOGA) was characterized using XRD, FTIR, HRTEM, Raman, and UV/Vis spectroscopy. The release study shows that the release of GA from the designed anticancer nanocomposite (GOGA) occurs in a sustained manner in phosphate-buffered saline (PBS) solution at pH 7.4. In in vitro biological studies, normal fibroblast (3T3) and liver cancer cells (HepG2) were treated with different concentrations of GO, GOGA, and GA for 72 h. The GOGA nanocomposite showed the inhibitory effect to cancer cell growth without affecting normal cell growth. The results of this research are highly encouraging to go further for in vivo studies

Prunella vulgaris: A comprehensive review of chemical constituents, pharmacological effects and clinical applications.

Prunella vulgaris (PV) is a perennial herb belonging to the Labiate family and is widely distributed in northeastern Asian countries such as Korea, Japan, and China. It is reported to display diverse biological activities including anti-microbial, anti-cancer, and anti-inflammation as determined by in vitro or in vivo studies. So far, about 200 compounds have been isolated from PV plant and majority of these have been characterized mainly as triterpenoids, sterols and flavonoids, followed by coumarins, phenylpropanoids, polysaccharides and volatile oils. This review summarizes and analyzes the current knowledge on the chemical constituents, pharmacological activities, mechanisms of action and clinical applications of the PV plant including its potential as a future medicinal plant. Although some of the chemical constituents of the PV plant and their mechanism of action have been investigated the biological activities of many of these remain unknown and further clinical trials are required to further enhance its reputation as a medicinal plant

Phytobioactive compound-based nanodelivery systems for the treatment of type 2 diabetes mellitus – current status

Palanivel Ganesan,1,2 Palanisamy Arulselvan,3 Dong-Kug Choi1,2 1Nanotechnology Research Center and Department of Applied Life Science, 2Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Republic of Korea; 3Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells. However, the poor solubility and lower permeability of these phyto products results in a loss of bioactivity during processing and oral delivery, leading to a significant reduction in the bioavailability of phytobioactive compounds to treat T2DM. Recently, nanotechnological systems have been developed for use as various types of carrier systems to improve the delivery of bioactive compounds and thus obtain a greater bioavailability. Furthermore, carrier systems in most nanodelivery systems are highly biocompatible, with nonimmunologic behavior, a high degree of biodegradability, and greater mucoadhesive strength. Therefore, this review focuses on the various types of nanodelivery systems that can be used for phytobioactive compounds in treating T2DM with greater antidiabetic effects. There is also additional focus on improving the effects of various phytobioactive compounds through nanotechnological delivery to ensure a highly efficient treatment of type 2 diabetes. Keywords: type 2 diabetes, nanodelivery system, phytobioactive compounds, oral deliver

Characterization and in vitro studies of the anticancer effect of oxidized carbon nanotubes functionalized with betulinic acid

Julia M Tan,1 Govindarajan Karthivashan,2 Palanisamy Arulselvan,2 Sharida Fakurazi,2,3 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience (IBS), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Among the array of nanomaterials, carbon nanotubes have shown great potential as drug carriers in the field of nanomedicine, owing to their attractive physicochemical structure, which facilitates functionalization of therapeutic molecules onto their external walls or being encapsulated inside the tubes. The aim of this preliminary study was to formulate betulinic acid (BA), a poorly water-soluble drug, in oxidized multiwalled carbon nanotubes (MWCNT-COOH) for enhanced delivery efficiency into cancer cells with reduced cytotoxicity. The synthesized MWCNT-BA nanocomposite was characterized using ultraviolet-visible, Fourier transform infrared, thermogravimetric analysis, powder X-ray diffraction, and field emission scanning electron microscopy techniques. The loading of BA in MWCNT-COOH nanocarrier was estimated to be about 14.5%–14.8% (w/w), as determined by ultraviolet-visible and thermogravimetric analysis. Fourier transform infrared study shows that the peaks of the resulting MWCNT-BA nanocomposite correlate to the characteristic functional groups of BA and MWCNT-COOH. The powder X-ray diffraction results confirmed that the tubular structures of MWCNT-COOH were not affected by the drug loading mechanism of BA. The release profiles demonstrated that approximately 98% of BA could be released within 22 hours by phosphate-buffered saline solution at pH 7.4 compared with about 22% within 24 hours at pH 4.8. The biocompatibility studies revealed that MWCNT-BA at concentrations <50 µg/mL expressed no cytotoxicity effects for mouse embryo fibroblast cells after 72 hours of treatment. The anticancer activity of MWCNT-BA was observed to be more sensitive to human lung cancer cell line when compared with human liver cancer cell line, with half maximal inhibitory concentration values of 2.7 and 11.0 µg/mL, respectively. Our findings form a fundamental platform for further investigation of the MWCNT-BA formulation against different types of cancer cells. Keywords: multiwalled carbon nanotubes (MWCNTs), drug delivery, controlled release, cytotoxicity, A549 cell line, HepG2 cell lin

Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model

Abubakar Amali Muhammad,1 Palanisamy Arulselvan,1 Cheah Pike See,2 Farida Abas,3 Sharida Fakurazi1,2 1Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, 2Unit of Anatomy, Department of Human Anatomy, Faculty of Medicine and Health Sciences, 3Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%–24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera containing Vicenin-2 active compound may accelerate wound healing in hyperglycemic condition. Keywords: aqueous fraction, Vicenin-2, wound healing, inflammatory mediators&nbsp