Search results for: bioactivity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 113

Search results for: bioactivity

53 Structure-Based Virtual Screening and in Silico Toxicity Test of Compounds against Mycobacterium tuberculosis 7,8-Diaminopelargonic Acid Aminotransferase (MtbBioA)

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

Abstract:

One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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52 Efficient Production of Cell-Adhesive Motif From Human Fibronectin Domains to Design a Bio-Functionalized Scaffold for Tissue Engineering

Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

Abstract:

Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

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51 Isolation, Characterization and Quantitation of Anticancer Constituent from Chloroform Extract of N. arbortristis L. Leaves

Authors: Parul Grover, K. A. Suri, Raj Kumar, Gulshan Bansal

Abstract:

Background: Nyctanthes arbortristis Linn is traditionally used as anticancer herb in Indian system of medicine, but its introduction into modern system of medicine is still awaited due to lack of systematic scientific studies. Objective: The objective of the present study was to isolate and characterize anticancer phytoconstituents from N. arbortristis L. leaves based on bioactivity guided fractionation. Method: Different extracts of the leaves of the plant were prepared by Soxhlet extractor. Each extract was evaluated for anticancer activity against HL-60 cell lines. Chloroform and HA extract showed potent anticancer activity and hence were selected for fractionation. Fraction C1 from chloroform extract was found to be most potent amongst all when tested against three cell lines (HL-60, A-549, and HCT-116) and thus was selected for further fractionation and a pure compound CP-01 was isolated. RP-HPLC method has been developed for quantification of isolated compound by using Kinetex C-18 column with gradient elution at 0.7 mL/min using mobile phase containing potassium dihydrogen phosphate (0.01 M, pH 3.0) with acetonitrile. The wavelength of maximum absorption (λₘₐₓ) selected was 210 nm. Results: The structure of potent anticancer CP-01 was determined on the basis spectroscopic methods like IR, 1H-NMR, ¹³C-NMR and Mass Spectrometry and it was characterized as 1,1,2-tris(2’,4’-di-tert-butylbenzene)-4,4-dimethyl-pent-1-ene. The content of CP-01 was found to be 0.88 %w/w of chloroform extract and 0.08 %w/w of N.arbortristis leaves. Conclusion: The study supports the traditional use of N. arbortristis as anticancer herb & the identified compound CP-01 can serve as an excellent lead to develop potent and safe anticancer drugs.

Keywords: anticancer, HL-60 cell lines, Nyctanthes arbor-tristis, RP-HPLC

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50 Agarose Based Multifunctional Nanofibrous Bandages for Wound Healing Applications

Authors: Sachin Latiyan, T. S. Sampath Kumar, Mukesh Doble

Abstract:

Natural polymer based nanofibrous wound dressings have gained increased attention because of their high surface area, bioactivity, biodegradability and resemblance to extracellular matrix. Agarose (a natural polymer) have been used largely for angiogenesis, cartilage formation and wound healing applications. However, electrospinning of agarose is tedious thereby rendering limited studies on fabrication and evaluation of agarose based nanofibrous wound dressings. Thus, present study focuses on the fabrication of agarose (10% w/v)/ polyvinyl alcohol (12% w/v) based multifunctional nanofibrous scaffolds. Zinc citrate (1, 3 and 5% w/w of the polymer) was added as a potential antibacterial agent to combat wound infections. The fabricated scaffolds exhibit ~500% swelling (in phosphate buffer saline) with enhanced mechanical strength which is suitable for most of the wound healing applications. In vitro studies were found to reveal an increased migration and proliferation of L929 mouse fibroblasts with agarose blends w.r.t to the control. The fabricated dressings were found to be effective against both Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacterial strains. Hence, a multifunctional (as provides effective swelling and mechanical support along with antibacterial property), natural product based, eco-friendly scaffold was successfully fabricated to serve as a potential wound dressing material.

Keywords: antibacterial dressings, benign solvent, nanofibrous agarose, biocompatibility, enhanced swelling and mechanical strength, biopolymeric dressings

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49 Evaluation of the Antibacterial Activity of New Dermaseptin Derivatives Against Acinetobacter Baumannii

Authors: Houda Haddad, Radhia Mejri, , Alyne Rodrigues de Araujo, Amira Zairi

Abstract:

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR), and for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these dermaseptins was investigated on the HEp-2 cell line by the MTT cell viability assay. Thereafter, we studied morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibit antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections.

Keywords: dermaseptin B2, dermaseptin S4, analogs, Acinetobacter baumannii, healthcare-associated infections, antibacterial activity

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48 Bioactive Compounds Characterization of Cereal-based Porridge Enriched with Cirina Forda

Authors: Kunle Oni

Abstract:

This study investigated the bioactivity potentials of porridge from yellow maize and malted sorghum enriched with Cirinaforda.All the samples were analyzed using standard methods.Results showed that the highest value 217.03μmolTEAC/100g, 43.3 mmol Fe2+ /100g, and 35.56% for DPPH, FRAP and TBARS respectively were reported in sample 50FYM+20MS+30CF, while the lowest value 146.10μmolTEAC/100, 20.18±0.11 mmol Fe2+/100g and 13.25% for DPPH, FRAP and TBARS were reported in the control sample.The oxalate and tannin contents were lowest in sample 50FYM+20MS+30CFbutOxalate was highest in the control sample while tannin was highest in sample 60FYM+20MS+20CF.The phytate content was highest in the 60FYM+20MS+20CF mixture (2.32 mg/100g) and lowest in the control (100% FYM) porridge (2.20 mg/100g).The result also showed that the total phenolic content was highest in the 60FYM+20MS+20CF mixture (318.28 mg GAE/100g) and lowest in the50FYM+30MS+20CF mixture (264.18mg GAE/100g).The total flavonoid content had the50FYM+20MS+30CFmixture having the highest content (189.31mg RE/100g) and the 60FYM+20MS+20CF mixture having the lowest (90.10mg RE/100g). The enrichment of the porridge with C. fordaincreased the concentration of various bioactive compounds compared to the control sample. The identified compounds cinnamic acid, methyl ester, 10-Methyl-E-11-tridecen-1-ol propionate, methaqualone,3-(2-Hydroxy-6-methylphenyl)-4(3H)-quinazolinone, and oleic acid

Keywords: bioactive compounds, characterization, cereal-based porridge, Cirina forda

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47 Vascularized Adipose Tissue Engineering by Using Adipose ECM/Fibroin Hydrogel

Authors: Alisan Kayabolen, Dilek Keskin, Ferit Avcu, Andac Aykan, Fatih Zor, Aysen Tezcaner

Abstract:

Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, only very thin implants can be used in vivo since vascularization is still a problem for thick implants. Another problem is finding a biocompatible scaffold with good mechanical properties. In this study, the aim is to develop a thick vascularized adipose tissue that will integrate with the host, and perform its in vitro and in vivo characterizations. For this purpose, a hydrogel of decellularized adipose tissue (DAT) and fibroin was produced, and both endothelial cells and adipocytes that were differentiated from adipose derived stem cells were encapsulated in this hydrogel. Mixing DAT with fibroin allowed rapid gel formation by vortexing. It also provided to adjust mechanical strength by changing fibroin to DAT ratio. Based on compression tests, gels of DAT/fibroin ratio with similar mechanical properties to adipose tissue was selected for cell culture experiments. In vitro characterizations showed that DAT is not cytotoxic; on the contrary, it has many natural ECM components which provide biocompatibility and bioactivity. Subcutaneous implantation of hydrogels resulted with no immunogenic reaction or infection. Moreover, localized empty hydrogels gelled successfully around host vessel with required shape. Implantations of cell encapsulated hydrogels and histological analyses are under study. It is expected that endothelial cells inside the hydrogel will form a capillary network and they will bind to the host vessel passing through hydrogel.

Keywords: adipose tissue engineering, decellularization, encapsulation, hydrogel, vascularization

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46 Isolation, Purification and Characterisation of Non-Digestible Oligosaccharides Derived from Extracellular Polysaccharide of Antarctic Fungus Thelebolus Sp. IITKGP-BT12

Authors: Abinaya Balasubramanian, Satyabrata Ghosh, Satyahari Dey

Abstract:

Non-Digestible Oligosaccharides(NDOs) are low molecular weight carbohydrates with degree of polymerization (DP) 3-20, that are delivered intact to the large intestine. NDOs are gaining attention as effective prebiotic molecules that facilitate prevention and treatment of several chronic diseases. Recently, NDOs are being obtained by cleaving complex polysaccharides as it results in high yield and also as the former tend to display greater bioactivity. Thelebolus sp. IITKGP BT-12, a recently identified psychrophilic, Ascomycetes fungus has been reported to produce a bioactive extracellular polysaccharide(EPS). The EPS has been proved to possess strong prebiotic activity and anti- proliferative effects. The current study is an attempt to identify and optimise the most suitable method for hydrolysis of the above mentioned novel EPS into NDOs, and further purify and characterise the same. Among physical, chemical and enzymatic methods, enzymatic hydrolysis was identified as the best method and the optimum hydrolysis conditions obtained using response surface methodology were: reaction time of 24h, β-(1,3) endo-glucanase concentration of 0.53U and substrate concentration of 10 mg/ml. The NDOs were purified using gel filtration chromatography and their molecular weights were determined using MALDI-TOF. The major fraction was found to have a DP of 7,8. The monomeric units of the NDOs were confirmed to be glucose using TLC and GCMS-MS analysis. The obtained oligosaccharides proved to be non-digestible when subjected to gastric acidity, salivary and pancreatic amylases and hence could serve as efficient prebiotics.

Keywords: characterisation, enzymatic hydrolysis, non-digestible oligosaccharides, response surface methodology

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45 Self-Organized TiO₂–Nb₂O₅–ZrO₂ Nanotubes on β-Ti Alloy by Anodization

Authors: Muhammad Qadir, Yuncang Li, Cuie Wen

Abstract:

Surface properties such as topography and physicochemistry of metallic implants determine the cell behavior. The surface of titanium (Ti)-based implant can be modified to enhance the bioactivity and biocompatibility. In this study, a self-organized titania–niobium pentoxide–zirconia (TiO₂–Nb₂O₅–ZrO₂) nanotubular layer on β phase Ti35Zr28Nb alloy was fabricated via electrochemical anodization. Energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle measurement techniques were used to investigate the nanotubes dimensions (i.e., the inner and outer diameters, and wall thicknesses), microstructural features and evolution of the hydrophilic properties. The in vitro biocompatibility of the TiO₂–Nb₂O₅–ZrO₂ nanotubes (NTs) was assessed by using osteoblast cells (SaOS2). Influence of anodization parameters on the morphology of TiO₂–Nb₂O₅–ZrO₂ NTs has been studied. The results indicated that the average inner diameter, outer diameter and the wall thickness of the TiO₂–Nb₂O₅–ZrO₂ NTs were ranged from 25–70 nm, 45–90 nm and 5–13 nm, respectively, and were directly influenced by the applied voltage during anodization. The average inner and outer diameters of NTs increased with increasing applied voltage, and the length of NTs increased with increasing anodization time and water content of the electrolyte. In addition, the size distribution of the NTs noticeably affected the hydrophilic properties and enhanced the biocompatibility as compared with the uncoated substrate. The results of this study could be considered for developing nano-scale coatings for a wide range of biomedical applications.

Keywords: Titanium alloy, TiO₂–Nb₂O₅–ZrO₂ nanotubes, anodization, surface wettability, biocompatibility

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44 Effect of B2O3 Addition on Sol-gel Synthesized 45S5 Bioglass

Authors: P. Dey, S. K. Pal

Abstract:

Ceramics or glass ceramics with the property of bone bonding at the nearby tissues and producing possible bone in growth are known to be bioactive. The most extensively used glass in this context is 45S5 which is a silica based bioglass mostly explored in the field of tissue engineering as scaffolds for bone repair. Nowadays, the borate based bioglass are being utilized in orthopedic area largely due to its superior bioactivity with the formation of bone bonding. An attempt has been made, in the present study, to observe the effect of B2O3 addition in 45S5 glass and perceive its consequences on the thermal, mechanical and biological properties. The B2O3 was added in 1, 2.5, and 5 wt% with simultaneous reduction in the silica content of the 45S5 composition. The borate based bioglass has been synthesized by the means of sol-gel route. The synthesized powders were then thermally analyzed by DSC-TG. The as synthesized powders were then calcined at 600ºC for 2hrs. The calcined powders were then pressed into pellets followed by sintering at 850ºC with a holding time of 2hrs. The phase analysis and the microstructural analysis of the as synthesized and calcined powder glass samples and the sintered glass samples were being carried out using XRD and FESEM respectively. The formation of hydroxyapatite layer was performed by immersing the sintered samples in the simulated body fluid (SBF) and mechanical property has been tested for the sintered samples by universal testing machine (UTM). The sintered samples showed the presence of sodium calcium silicate phase while the formation of hydroxyapaptite takes place for SBF immersed samples. The formation of hydroxyapatite is more pronounced in case of borated based glass samples instead of 45S5.

Keywords: 45S5 bioglass, bioactive, borate, hydroxyapatite, sol-gel synthesis

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43 Bifunctional Electrospun Fibers Based on Poly(Lactic Acid)/Calcium Oxide Nanocomposites as a Potential Scaffold for Bone Tissue Engineering

Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

Abstract:

Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

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42 Biocellulose Template for 3D Mineral Scaffolds

Authors: C. Busuioc, G. Voicu, S. I. Jinga

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The field of tissue engineering brings new challenges in terms of proposing original solutions for ongoing medical issues, improving the biological performances of existing clinical systems and speeding the healing process for a faster recovery and a more comfortable life as patient. In this context, we propose the obtaining of 3D porous scaffolds of mineral nature, dedicated to bone repairing and regeneration purposes or employed as bioactive filler for bone cements. Thus, bacterial cellulose - calcium phosphates composite materials have been synthesized by successive immersing of the polymeric membranes in the precursor solution containing Ca2+ and [PO4]3- ions. The mineral phase deposited on the surface of biocellulose fibers was varied as amount through the number of immersing cycles. The intermediary composites were subjected to thermal treatments at different temperatures in order to remove the organic part and provide the formation of a self-sustained 3D architecture. The resulting phase composition consists of common phosphates, while the morphology largely depends on the preparation parameters. Thus, the aspect of the 3D mineral scaffolds can be tuned from a loose microstructure composed of large grains connected via monocrystalline nanorods to a trabecular pattern crossed by parallel internal channels, just like the natural bone. The bioactivity and biocompatibility of the obtained materials have been also assessed, with encouraging results in the clinical use direction. In conclusion, the compositional, structural, morphological and biological characterizations sustain the suitability of the reported biostructures for integration in hard tissue engineering applications.

Keywords: bacterial cellulose, bone reconstruction, calcium phosphates, mineral scaffolds

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41 Chemical Composition, Antioxidant and Antibacterial Activities of Essential Oil from the Leaves of Thymus vulgaris L.

Authors: Tsige Reda

Abstract:

Essential oil of Thymus vulgaris was extracted by means of hydro-distillation. This study was done to investigate the chemical composition, antibacterial and antioxidant activities. The chemical composition of the essential oils was determined using gas chromatography coupled to mass spectroscopy (GC-MS). Using disc diffusion assay the antibacterial activity was assessed on one Gram-positive bacteria and one Gram-negative bacteria. The percentage oil yield of the essential oil was found to be 0.97 ± 0.08% (w/w) with yellow color. The physicochemical constants of the oil were also noted. The phytochemical screening of the plant extract revealed the presence of tannins, saponins, phenol, flavonoids, terpenoids, steroids and alkaloids. A total of 18 chemical constituents were identified by Gas Chromatography-Mass Spectroscopy analysis representing 100% of the total essential oil of Thymus vulgaris, with thymol (31.977%), o-cymene (29.992%), and carvacrol (14.541%). Previous studies have revealed that the thymol, o-cymen and carvacrol components of Thymus vulgaris are responsible for their biological activities. Thymus vulgaris have been used traditionally to treat a wide variety of infections. Based on the extensive use and lack of scientific evidence, a study was embarked upon to determine its bioactivity. The essential oil of Thymus vulgaris leaves exhibited higher activity towards the Gram-positive bacteria (Staphylococcus aurous) than the Gram-negative bacteria (Escherichia coli) and also has good antioxidant activity, and can be used medicinal and therapeutic applications. This activity may be due to the high amount of thymol, o-cymen and carvacrol.

Keywords: hydro-distillation, Thymus vulgaris, essential oil composition, phytochemical screening, physicochemical constants, antioxidant activity, antibacterial activity

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40 Fabrication of Cheap Novel 3d Porous Scaffolds Activated by Nano-Particles and Active Molecules for Bone Regeneration and Drug Delivery Applications

Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

Abstract:

Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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39 The Prodomain-Bound Form of Bone Morphogenetic Protein 10 is Biologically Active on Endothelial Cells

Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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38 Phytochemical Composition and Characterization of Bioactive Compounds of the Green Seaweed Ulva lactuca: A Phytotherapeutic Approach

Authors: Mariame Taibi, Marouane Aouiji, Rachid Bengueddour

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The Moroccan coastline is particularly rich in algae and constitutes a reserve of species with considerable economic, social and ecological potential. This work focuses on the research and characterization of algae bioactive compounds that can be used in pharmacology or phytopathology. The biochemical composition of the green alga Ulva lactuca (Ulvophyceae) was studied by determining the content of moisture, ash, phenols, flavonoids, total tannins, and chlorophyll. Seven solvents: distilled water, methanol, ethyl acetate, chloroform, benzene, petroleum ether, and hexane, were tested for their effectiveness in recovering chemical compounds. The identification of functional groupings, as well as the bioactive chemical compounds, was determined by FT-IR and GC-MS. The moisture content of the alga was 77%, while the ash content was 15%. Phenol content differed from one solvent studied to another, while chlorophyll a, b, and total chlorophyll were determined at 14%, 9.52%, and 25%, respectively. Carotenoid was present in a considerable amount (8.17%). The experimental results show that methanol is the most effective solvent for recovering bioactive compounds, followed by water. Moreover, the green alga Ulva lactuca is characterized by a high level of total polyphenols (45±3.24 mg GAE/gDM), average levels of total tannins and flavonoids (22.52±8.23 mg CE/gDM, 15.49±0.064 mg QE/gDM) respectively. The results of Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of alcohol/phenol and amide functions in Ulva lactuca. The GC-MS analysis gave precisely the compounds contained in the various extracts, such as phenolic compounds, fatty acids, terpenoids, alcohols, alkanes, hydrocarbons, and steroids. All these results represent only a first step in the search for biologically active natural substances from seaweed. Additional tests are envisaged to confirm the bioactivity of seaweed.

Keywords: algae, Ulva lactuca, phenolic compounds, FTIR, GC-MS

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37 Synthesis and Biological Activities of Novel -1,2,3-Triazoles Derivatives

Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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36 In Vivo Response of Scaffolds of Bioactive Glass-Ceramic

Authors: Ana Claudia Muniz Rennó, Karina Nogueira

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This study aimed to investigate the in vivo tissue response of the introduction of the bioactive mesh (BM) scaffolds using a model of tibial bone defect implants in rats. Although a previous in vivo study demonstrated a highly positive response of particulate bioactive materials in the morphological and biomechanical properties of the bone callus, the effects of material with superior bioactivity, present in form of meshes have not been studied yet. Eighty male Wistar rats with 3 mm tibial defects were used. Animals were divided into four groups: intact group (IG) – tibia without any injury; bone defect day zero (0dD) – bone defects, sacrificed immediately after injury; bone defect control group (CG) – bone defects without any filler and bone defect filled with BM scaffold. The animals of BM and CG groups were sacrificed 15, 30 and 45 days post-injury to compare the temporal-special effects of the scaffolds on bone healing. The histological analysis revealed an organized newly formed bone at 30 and 45 days post-surgery in the BM. Also, this group presented an increased COX-2 expression on days 15 and 30 post-surgery. Furthermore, the immunohistochemistry analysis revealed that, BM presented a positive immunoexpression of RUNX-2 during all periods evaluated. The biomechanical analysis revealed that at 15 day after surgery, no significant statistically difference was observed between BM and CG and both groups had significantly higher values of maximal load compared to 0dG and significantly lower values than IG. On days 30 and 45 post-surgery, BM presented statistically lower values of maximal load compared to the CG. Nevertheless, at the same periods, BM did not show statistically significant difference compared to the IG maximal load values (p > 0, 05). Our results revealed that the implantation of the BM scaffolds was effective in stimulating newly bone formation.

Keywords: bone, biomaterials, scaffolds, cartilage

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35 Sensitizing Bamboo Fabric with Antimicrobial Turmeric Dye

Authors: Varinder Kaur, Amanjit Kaur, Simran Kaur, Samriti Vaid

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Coating of fabrics with anti-microbial dyes is an adaptable technique of protection from various diseases. Natural dyes, which are known to possess antibacterial properties, can be used for antibacterial finishing of fibers like cotton, wool, bamboo and so many. Dyeing of fabrics with natural dyes normally requires the use of mordants so that dyes can stay on the fabric as well as into interstices of the fabric during multiple washings. In this study, the mordants used are alum and chitosan for ensuring a reasonable color fastness to light and washing. Chitosan is a natural polysaccharide having significant biological and chemical properties such as biodegradability, biocompatibility, bioactivity, microbial activity and polycationicity. The metal ion of alum mordant can act as electron acceptor for electron donor to form coordination bond with the dye molecule, making them insoluble in water. The dyeing of bamboo fabric using a natural dye extracted from turmeric has been studied using conventional dyeing method. Natural dye was extracted using water as solvent by Soxhlet extraction method. The extracted color was characterized by spectroscopic studies like UV/visible and further tested for antimicrobial activity. The effect of mordants on the dyeing outcome in terms of colour depth as well as fastness properties of the dyeing was investigated. It has been found that employing the conventional dyeing technique at 100 oC, the mordanted samples were deeper in depth than their unmordanted counterparts. The results of fastness properties of the dyed fabrics were fair to good. Turmeric extract was found to enhance microbial resistance of bamboo as well as was itself as a good cause of coloration. These textiles dyed with the turmeric as natural dye can be very useful in developing clothing for infants, elderly and infirm people to protect them against common infections. The outcome of this study will provide a new feature to the interface of dyeing and pharmaceutical industry.

Keywords: antimicrobial activity, bamboo fabric, natural dye, turmeric

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34 Feasibility of Phenolic Acids Rich Fraction from Gynura procumbens as Potential Antihyperlipidemic Agent

Authors: Vikneswaran Murugaiyah, Sultan Ayesh Mohammed Saghir, Kisantini Murugesu, Mohd. Zaini Asmawi, Amirin Sadikun

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Gynura procumbens is a popular medicinal plant used as a folk medicine in Southeast Asia to treat kidney diseases, diabetes mellitus and hyperlipidemia. The present study aims to investigate the antihyperlipidemic potential of phenolic acids rich fraction (PARF) from G. procumbens in chemically-induced acute and high fat diet-induced chronic hyperlipidemic rats. Ethanolic extract of G. procumbens leaves exhibited significant reductions in total cholesterol (TC) and triglycerides (TG) levels (P < 0.01 and P < 0.001, respectively) of poloxamer 407-induced rats compared to hyperlipidemic control after 58 h of treatment. Upon bioactivity guided fractionation the antihyperlipidemic activity was found to be concentrated in the PARF, which significantly reduced the TC and TG levels (P < 0.001). HPLC analysis revealed that 3,5-dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid and chlorogenic acid are the major compounds in the PARF. Likewise, chlorogenic acid (60 mg/kg) exhibited significant reductions in TC and TG levels of hyperlipidemic rats (P < 0.001). Both chlorogenic acid and PARF significantly reduced LDL, VLDL and atherogenic index (P<0.01), while PARF increased the HDL (P < 0.01) compared to hyperlipidemic control. Both were found to be not cytotoxic against normal and cancer cell lines. In addition, LD50 of orally administered PARF was more than 5,000 mg/kg. Further investigation in high fat diet-induced chronic hyperlipidemic rats revealed that chronic administration of PARF dose-dependently restored the increase in lipids parameters. In summary, the phenolic acids rich fraction of G. procumbens leaves showed promising antihyperlipidemic effect in both chemically- and diet-induced hyperlipidemic rats that warrants further elucidation on its mechanisms of action.

Keywords: Antihyperlipidemic, Gynura procumbens, phenolic acids, chlorogenic acid, poloxamer-407, high fat diet

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33 Antimicrobial, Antioxidant and Cytotoxic Activities of Cleoma viscosa Linn. Crude Extracts

Authors: Suttijit Sriwatcharakul

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The bioactivity studies from the weed ethanolic crude extracts from leaf, stem, pod and root of wild spider flower; Cleoma viscosa Linn. were analyzed for the growth inhibition of 6 bacterial species; Salmonella typhimurium TISTR 5562, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus TISTR 1466, Streptococcus epidermidis ATCC 1228, Escherichia coli DMST 4212 and Bacillus subtilis ATCC 6633 with initial concentration crude extract of 50 mg/ml. The agar well diffusion results found that the extracts inhibit only gram positive bacteria species; S. aureus, S. epidermidis and B. subtilis. The minimum inhibition concentration study with gram positive strains revealed that leaf crude extract give the best result of the lowest concentration compared with other plant parts to inhibit the growth of S. aureus, S. epidermidis and B. subtilis at 0.78, 0.39 and lower than 0.39 mg/ml, respectively. The determination of total phenolic compounds in the crude extracts exhibited the highest phenolic content was 10.41 mg GAE/g dry weight in leaf crude extract. Analyzed the efficacy of free radical scavenging by using DPPH radical scavenging assay with all crude extracts showed value of IC50 of leaf, stem, pod and root crude extracts were 8.32, 12.26, 21.62 and 35.99 mg/ml, respectively. Studied cytotoxicity of crude extracts on human breast adenocarcinoma cell line by MTT assay found that pod extract had the most cytotoxicity CC50 value, 32.41 µg/ml. Antioxidant activity and cytotoxicity of crude extracts exhibited that the more increase of extract concentration, the more activities indicated. According to the bioactivities results, the leaf crude extract of Cleoma viscosa Linn. is the most interesting plant part for further work to search the beneficial of this weed.

Keywords: antimicrobial, antioxidant activity, Cleoma viscosa Linn., cytotoxicity test, total phenolic compound

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32 Exploring Marine Bacteria in the Arabian Gulf Region for Antimicrobial Metabolites

Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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31 Poly(L-Lactic Acid) Scaffolds for Bone Tissue Engineering

Authors: Aleksandra BužArovska, Gordana Bogoeva Gaceva

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Biodegradable polymers have received significant scientific attention in tissue engineering (TE) application, in particular their composites consisting of inorganic nanoparticles. In the last 15 years, they are subject of intensive research by many groups, aiming to develop polymer scaffolds with defined biodegradability, porosity and adequate mechanical stability. The most important characteristic making these materials attractive for TE is their biodegradability, a process that could be time controlled and long enough to enable generation of a new tissue as a replacement for the degraded polymer scaffold. In this work poly(L-lactic acid) scaffolds, filled with TiO2 nanoparticles functionalized with oleic acid, have been prepared by thermally induced phase separation method (TIPS). The functionalization of TiO2 nanoparticles with oleic acid was performed in order to improve the nanoparticles dispersibility within the polymer matrix and at the same time to inhibit the cytotoxicity of the nanofiller. The oleic acid was chosen as amphiphilic molecule belonging to the fatty acid family because of its non-toxicity and possibility for mediation between the hydrophilic TiO2 nanoparticles and hydrophobic PLA matrix. The produced scaffolds were characterized with thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and mechanical compression measurements. The bioactivity for bone tissue engineering application was tested in supersaturated simulated body fluid. The degradation process was followed by Fourier transform infrared spectroscopy (FTIR). The results showed anisotropic morphology with elongated open pores (100 µm), high porosity (around 92%) and perfectly dispersed nanofiller. The compression moduli up to 10 MPa were identified independent on the nanofiller content. Functionalized TiO2 nanoparticles induced formation of hydroxyapatite clusters as much as unfunctionalized TiO2. The prepared scaffolds showed properties ideal for scaffold vascularization, cell attachment, growth and proliferation.

Keywords: biodegradation, bone tissue engineering, mineralization, PLA scaffolds

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30 Evaluation of the Antiviral Activity of Dermaseptin Analogs Against Zika Virus

Authors: Houda Haddad, Nolwen Jouvenet, Maxime Chazal, Frédéric Tangy, Amira Zairi

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Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders, such as microcephaly and Guillain-Barré syndrome, affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on the HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations except for dermaseptin B2 and its derivative, which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from the S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 μg/mL, unlike the native B2 and its derivative, which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as lead structures for the development of potent antiviral agents against Zika virus infections.

Keywords: dermaseptin B2, dermaseptin S4, analogs, zika virus, neurological infections, antiviral activity

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29 Role of Onion Extract for Neuro-Protection in Experimental Stroke Model

Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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28 Phytochemical Content and Bioactive Properties of Wheat Sprouts

Authors: Jasna Čanadanović-Brunet, Lidija Jevrić, Gordana Ćetković, Vesna Tumbas Šaponjac, Jelena Vulić, Slađana Stajčić

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Wheat contains high amount of nutrients such as dietary fiber, resistant starch, vitamins, minerals and microconstituents, which are building blocks of body tissues, but also help in the prevention of diseases such as cardiovascular disease, cancer and diabetes. Sprouting enhances the nutritional value of whole wheat through biosynthesis of tocopherols, polyphenols and other valuable phytochemicals. Since the nutritional and sensory benefits of germination have been extensively documented, using of sprouted grains in food formulations is becoming a trend in healthy foods. The present work addressed the possibility of using freeze-dried sprouted wheat powder, obtained from spelt-wheat cv. ‘Nirvana’ (Triticum spelta L.) and winter wheat cv. ‘Simonida’ (Triticum aestivum L. ssp. vulgare var. lutescens), as a source of phytochemicals, to improve the functional status of the consumer. The phytochemicals' content (total polyphenols, flavonoids, chlorophylls and carotenoids) and biological activities (antioxidant activity on DPPH radicals and antiinflammatory activity) of sprouted wheat powders were assessed spectrophotometrically. The content of flavonoids (216.52 mg RE/100 g), carotenoids (22.84 mg β-carotene/100 g) and chlorophylls (131.23 mg/100 g), as well as antiinflammatory activity (EC50=3.70 mg/ml) was found to be higher in sprouted spelt-wheat powder, while total polyphenols (607.21 mg GAE/100 g) and antioxidant activity on DDPPH radicals (EC50=0.27 mmol TE/100 g) was found to be higher in sprouted winter wheat powders. Simulation of gastro-intestinal digestion of sprouted wheat powders clearly shows that intestinal digestion caused a higher release of polyphenols than gastric digestion for both samples, which indicates their higher bioavailability in the colon. The results of the current study have shown that wheat sprouts can provide a high content of phytochemicals and considerable bioactivities. Moreover, data reported show that they contain a unique pattern of bioactive molecules, which make these cereal sprouts attractive functional foods for a health-promoting diet.

Keywords: wheat, sprouts, phytochemicals, bioactivity

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27 Bioactive Secondary Metabolites from Culturable Unusual Actinomycetes from Solomon Islands Marine Sediments: Isolation and Characterisation of Bioactive Compounds

Authors: Ahilya Singh, Brad Carte, Ramesh Subramani, William Aalbersberg

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A total of 37 actinomycete strains were purified from 25 Solomon Islands marine sediments using four different types of isolation media. Among them, 54% of the strains had obligate requirement of seawater for growth. The ethyl acetate extract of 100 ml fermentation product of each strain was screened for antimicrobial activity against multidrug resistant human pathogens and cytotoxic activity against brine shrimps. A total of 67% of the ethyl acetate extracts showed antimicrobial and/or cytotoxic activities. A strain F-1915 was selected for isolation and evaluation of bioactive compound(s) based on its bioactive properties and chemical profile analysis using the LC-MS. The strain F-1915 was identified to have 96% sequence similarity to Streptomyces violaceusniger on the basis of 16S rDNA sequences using BLAST analysis. The 16S rDNA revealed that the strain F-1915 is a new member of MAR4 clade of actinomycetes. The MAR4 clade is an interesting clade of actinomycetes known for the production of pharmaceutically important hybrid isoprenoid compounds. The ethyl acetate extract of the fermentation product of this strain was purified by silica gel column chromatography and afforded the isolation of one bioactive pure compound. Based on the 1D and 2D NMR spectral data of compound 1 it was identified as a new mono-brominated phenazinone, Marinophenazimycin A, a structure which has already been studied by external collaborators at Scripps Institution of Oceanography but is yet to be published. Compound 1 displayed significant antimicrobial activity against drug resistant human pathogens. The minimum inhibitory concentration (MIC) of compound 1 was against Methicillin Resistant Staphylococcus aureus (MRSA) was about 1.9 μg/ml and MIC recorded against Amphotericin Resistant Candida albicans (ARCA) was about 0.24 μg/ml. The bioactivity of compound 1 against ARCA was found to be better than the standard antifungal agent amphotericin B. Compound 1 however did not show any cytotoxic activity against brine shrimps.

Keywords: actinomycetes, antimicrobial activity, brominated phenazine, MAR4 clade, marine natural products, multidrug resistent, 1D and 2D NMR

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26 Drug Design Modelling and Molecular Virtual Simulation of an Optimized BSA-Based Nanoparticle Formulation Loaded with Di-Berberine Sulfate Acid Salt

Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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25 Electrospun Fibre Networks Loaded with Hydroxyapatite and Barium Titanate as Smart Scaffolds for Tissue Regeneration

Authors: C. Busuioc, I. Stancu, A. Nicoara, A. Zamfirescu, A. Evanghelidis

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The field of tissue engineering has expanded its potential due to the use of composite biomaterials belonging to increasingly complex systems, leading to bone substitutes with properties that are continuously improving to meet the patient's specific needs. Furthermore, the development of biomaterials based on ceramic and polymeric phases is an unlimited resource for future scientific research, with the final aim of restoring the original tissue functionality. Thus, in the first stage, composite scaffolds based on polycaprolactone (PCL) or polylactic acid (PLA) and inorganic powders were prepared by employing the electrospinning technique. The targeted powders were: commercial and laboratory synthesized hydroxyapatite (HAp), as well as barium titanate (BT). By controlling the concentration of the powder within the precursor solution, together with the processing parameters, different types of three-dimensional architectures were achieved. In the second stage, both the mineral powders and hybrid composites were investigated in terms of composition, crystalline structure, and microstructure so that to demonstrate their suitability for tissue engineering applications. Regarding the scaffolds, these were proven to be homogeneous on large areas and loaded with mineral particles in different proportions. The biological assays demonstrated that the addition of inorganic powders leads to modified responses in the presence of simulated body fluid (SBF) or cell cultures. Through SBF immersion, the biodegradability coupled with bioactivity were highlighted, with fiber fragmentation and surface degradation, as well as apatite layer formation within the testing period. Moreover, the final composites represent supports accepted by the cells, favoring implant integration. Concluding, the purposed fibrous materials based on bioresorbable polymers and mineral powders, produced by the electrospinning technique, represent candidates with considerable potential in the field of tissue engineering. Future improvements can be attained by optimizing the synthesis process or by simultaneous incorporation of multiple inorganic phases with well-defined biological action in order to fabricate multifunctional composites.

Keywords: barium titanate, electrospinning, fibre networks, hydroxyapatite, smart scaffolds

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24 Development of Ferric Citrate Complex Draw Solute and Its Application for Liquid Product Enrichment through Forward Osmosis

Authors: H. Li, L. Ji, J. Su

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Forward osmosis is an emerging technology for separation and has great potential in the concentration of liquid products such as protein, pharmaceutical, and natural products. In pharmacy industry, one of the very tough talks is to concentrate the product in a gentle way since some of the key components may lose bioactivity when exposed to heating or pressurization. Therefore, forward osmosis (FO), which uses inherently existed osmosis pressure instead of externally applied hydraulic pressure, is attractive for pharmaceutical enrichments in a much efficient and energy-saving way. Recently, coordination complexes have been explored as the new class of draw solutes in FO processes due to their bulky configuration and excellent performance in terms of high water flux and low reverse solute flux. Among these coordination complexes, ferric citrate complex with lots of hydrophilic groups and ionic species which make them good solubility and high osmotic pressure in aqueous solution, as well as its low toxicity, has received much attention. However, the chemistry of ferric complexation by citrate is complicated, and disagreement prevails in the literature, especially for the structure of the ferric citrate. In this study, we investigated the chemical reaction with various molar ratio of iron and citrate. It was observed that the ferric citrate complex (Fe-CA2) with molar ratio of 1:1 for iron and citrate formed at the beginning of the reaction, then Fecit would convert to ferric citrate complex at the molar ratio of 1:2 with the proper excess of citrate in the base solution. The structures of the ferric citrate complexes synthesized were systematically characterized by X-ray diffraction (XRD), UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric analysis (TGA). Fe-CA2 solutions exhibit osmotic pressures more than twice of that for NaCl solutions at the same concentrations. Higher osmotic pressure means higher driving force, and this is preferable for the FO process. Fe-CA2 and NaCl draw solutions were prepared with the same osmotic pressure and used in FO process for BSA protein concentration. Within 180 min, BSA concentration was enriched from 0.2 to 0.27 L using Fe-CA draw solutions. However, it was only increased from 0.20 to 0.22 g/L using NaCl draw solutions. A reverse flux of 11 g/m²h was observed for NaCl draw solutes while it was only 0.1 g/m²h for Fe-CA2 draw solutes. It is safe to conclude that Fe-CA2 is much better than NaCl as draw solute and it is suitable for the enrichment of liquid product.

Keywords: draw solutes, ferric citrate complex, forward osmosis, protein enrichment

Procedia PDF Downloads 110