Retention behavior of nucleosides and nucleobases on a 3 µm undecylenic acid-functionalized silica column in per aqueous liquid chromatography and hydrophilic interaction liquid chromatography separation modes.

A 3 µm undecylenic acid-functionalized stationary phase (UAS) was prepared for the separation of nucleosides and nucleobases using per aqueous liquid chromatography (PALC) and hydrophilic interaction liquid chromatography (HILIC). The retention behaviors of nucleosides and nucleobases in PALC and HILIC modes were explored by adjusting parameters such as water content, buffer concentration, pH of the mobile phase and column temperature. The experimental data and separation chromatogram demonstrated that PALC could provide retention comparable to that of HILIC for nucleosides and nucleobases. Comparative studies using diluted adenosine solutions evaluated theoretical plates and peak shape for the same retention factors (between 0.25 and 5.0) in PALC and HILIC. There was no buffer component in the mobile phases used to operate the comparisons. HILIC mode is more efficient for adenosine than PALC mode at low retention factors. It's the exact opposite phenomenon for high retention factors. It is proposed that the mass transfer of adenosine between the UAS, the water-rich layer and the ACN-rich mobile phase in HILIC is relatively slow. Given the significant use of toxic ACN in HILIC, PALC emerges as a safer and more effective alternative for separating nucleosides and nucleobases.

Novel Formulation of Undecylenic Acid induces Tumor Cell Apoptosis.

Undecylenic acid, a monounsaturated fatty acid, is currently in clinical use as a topical antifungal agent, however the potential for therapeutic application in other disease settings has not been investigated. In this study, we describe a novel platform for the solubilization of fatty acids using amino acids and utilize this approach to define a tumoricidal activity and underlying mechanism for undecylenic acid. We examined a novel formulation of undecylenic acid compounded with L-Arginine, called GS-1, that induced concentration-dependent tumor cell death, with undecylenic acid being the cytotoxic component. Further investigation revealed that GS-1-mediated cell death was caspase-dependent with a reduction in mitochondrial membrane potential, suggesting a pro-apoptotic mechanism of action. Additionally, GS-1 was found to localize intracellularly to lipid droplets. In contrast to previous studies where lipid droplets have been shown to be protective against fatty acid-induced cell death, we showed that lipid droplets could not protect against GS-1-induced cytotoxicity. We also found a role for Fatty Acid Transport Protein 2 (FATP2) in the uptake of this compound. Collectively, this study demonstrates that GS-1 has effective pro-apoptotic antitumor activity in vitro and, together with the novel platform of fatty acid solubilization, contributes to the re-emerging field of fatty acids as potential anti-cancer therapeutics.

Molecular modeling and phenoloxidase inhibitory activity of arbutin and arbutin undecylenic acid ester.

Excessive melanin formation has been linked to various skin disorders such as hyperpigmentation and skin cancer. Tyrosinase is the most prominent target for inhibitors of melanin production. In this study, we investigated whether arbutin and its prodrug, arbutin undecylenic acid ester, might inhibit phenoloxidase (PO), a tyrosinase-like enzyme. Molecular docking simulation results suggested that arbutin and arbutin undecylenic acid ester can bind to the substrate-binding pocket of PO. Arbutin undecylenic acid ester with an IC50 6.34 mM was effective to inhibit PO compared to arbutin (IC50 29.42 mM). In addition, arbutin undecylenic acid ester showed low cytotoxicity in Drosophila S2 cells and the compound inhibited the melanization reaction. Therefore, the results of this study have demonstrated that arbutin undecylenic acid ester as a potential inhibitor of PO. We successfully designed a new platform utilizing Drosophila melanogaster and Bombyx mori as animal models propounding fast, cheap, and high effectiveness in method to screen tyrosinase inhibitors.

Effect of Polyhexamethylene Biguanide in Combination with Undecylenamidopropyl Betaine or PslG on Biofilm Clearance.

Hospital-acquired infection is a great challenge for clinical treatment due to pathogens' biofilm formation and their antibiotic resistance. Here, we investigate the effect of antiseptic agent polyhexamethylene biguanide (PHMB) and undecylenamidopropyl betaine (UB) against biofilms of four pathogens that are often found in hospitals, including Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, Gram-positive bacteria Staphylococcus aureus, and pathogenic fungus, Candida albicans. We show that 0.02% PHMB, which is 10-fold lower than the concentration of commercial products, has a strong inhibitory effect on the growth, initial attachment, and biofilm formation of all tested pathogens. PHMB can also disrupt the preformed biofilms of these pathogens. In contrast, 0.1% UB exhibits a mild inhibitory effect on biofilm formation of the four pathogens. This concentration inhibits the growth of S. aureus and C. albicans yet has no growth effect on P. aeruginosa or E. coli. UB only slightly enhances the anti-biofilm efficacy of PHMB on P. aeruginosa biofilms. However, pretreatment with PslG, a glycosyl hydrolase that can efficiently inhibit and disrupt P. aeruginosa biofilm, highly enhances the clearance effect of PHMB on P. aeruginosa biofilms. Meanwhile, PslG can also disassemble the preformed biofilms of the other three pathogens within 30 min to a similar extent as UB treatment for 24 h.

ω-hydroxyundec-9-enoic acid induction of breast cancer cells apoptosis through generation of mitochondrial ROS and phosphorylation of AMPK.

This study was performed to evaluate the anticancer effect of ω-hydroxyundec-9-enoic acid (ω-HUA), a microbial bio-catalyst product in breast cancer cells, through AMP-activated protein kinase (AMPK) regulation. ω-HUA mediated apoptosis was induced in breast cancer cells by AMPK activation, loss of mitochondrial membrane potential, and reactive oxygen species (ROS) generation. ω-HUA treatment of breast cancer cells increased the AMPK phosphorylation levels, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) proteins. In addition, anti-apoptotic members, such as Bcl-2, were downregulated, while Bax, a pro-apoptotic member, was upregulated. ω-HUA decreased the mitochondrial membrane potential while increasing the expression of cytochrome c (cyt c). Treating the cells with compound C, an AMPK inhibitor, reversed the phenomena, leading to an increase in cell viability and a decrease in apoptosis induction. Treating the cells with an ROS scavenger, N-acetyl cysteine (NAC), led to AMPK inactivation and apoptosis inhibition, allowing the recovery of cell health. In conclusion, ω-HUA sequentially caused the production of mitochondrial ROS and the consequent AMPK activation, thereby inducing apoptosis in breast cancer cells. Thus, ω-HUA may prove useful as an anticancer agent that targets AMPK in breast cancer cells.

Identification of undecylenic acid as EAG channel inhibitor using surface plasmon resonance-based screen of KCNH channels.

BACKGROUND: KCNH family of potassium channels is responsible for diverse physiological functions ranging from the regulation of neuronal excitability and cardiac contraction to the regulation of cancer progression. KCNH channels contain a Per-Arn-Sim (PAS) domain in their N-terminal and cyclic nucleotide-binding homology (CNBH) domain in their C-terminal regions. These intracellular domains shape the function of KCNH channels and are important targets for drug development. METHODS: Here we describe a surface plasmon resonance (SPR)-based screening method aimed in identifying small molecule binders of PAS and CNBH domains for three KCNH channel subfamilies: ether-à-go-go (EAG), EAG-related gene (ERG), and EAG-like K+ (ELK). The method involves purification of the PAS and CNBH domains, immobilization of the purified domains on the SPR senor chip and screening small molecules in a chemical library for binding to the immobilized domains using changes in the SPR response as a reporter of the binding. The advantages of this method include low quantity of purified PAS and CNBH domains necessary for the implementation of the screen, direct assessment of the small molecule binding to the PAS and CNBH domains and easiness of assessing KCNH subfamily specificity of the small molecule binders. RESULTS: Using the SPR-based method we screened the Spectrum Collection Library of 2560 compounds against the PAS and CNBH domains of the three KCNH channel subfamilies and identified a pool of small molecules that bind to the PAS or CNBH domains. To further evaluate the effectiveness of the screen we tested the functional effect of one of the identified mEAG PAS domain specific small molecule binders on currents recorded from EAG channels. Undecylenic acid inhibited currents recorded from EAG channels in a concentration-dependent manner with IC50 of ~ 1 µM. CONCLUSION: Our results show that the SPR-based method is well suited for identifying small molecule binders of KCNH channels and can facilitate drug discovery for other ion channels as well.

Evaluating the Effects of a Topical Preparation with Dexpanthenol, Silbiol, Undecylenic Acid, and Lidocaine on Palatal Mucosa Wound Healing in a Rat Model

Background: Postoperative complications occur after periodontal plastic surgeries, but an ideal treatment to overcome them has not been found yet. Aims: To evaluate the effects of topically applied Oral-norm gel on the healing of excisional wounds. Study Design: Animal experiment. Methods: Excisional wounds with a diameter of 3 mm were made in the center of the palatal mucosa of 63 Sprague Dawley rats. Seven animals were sacrificed at time 0. The remaining rats were divided into two groups: a test group in which the topical Oral-norm gel was applied three times a day and a control group in which nothing was applied. Seven animals in each group were sacrificed at 3, 7, 14, and 21 days. Mean wound surface area was measured photographically, while wound healing and width were evaluated microscopically. Results: The mean wound surface area decreased significantly after 3 days in both groups (p<0.001). Between days 3 and 7, the mean wound surface area decreased from 6.62 (2.85) to 0.83 (1.62) mm2 in the control group and 5.07 (0.88) to 1.42 (1.67) mm2 in the test group. The wound width decreased significantly on day 7 in both groups (p<0.001), with no further changes by day 14. Both groups had a significant increase in inflammation and vascularization on day 3 (p<0.001), with a reduction thereafter. No significant differences in macroscopic and microscopic measurements were observed between the groups at any time point (p>0.05). Conclusion: The Oral-norm gel has no positive healing effects in the palatal mucosa of rats.

Inhibition of Bromelain Activity During Enzymatic Debridement of Burn Wounds Pretreated With Frequently Used Products.

An enzyme mixture containing bromelain (NexoBrid®) was found to be suitable for enzymatic debridement of burn wounds, as determined by the criteria of patient comfort and pain, selectivity, and efficiency. Nevertheless, daily experience showed that pretreatment of burn wounds with several other clinical agents may inhibit debridement efficiency. Therefore, the current study was performed to identify those agents and evaluate their debridement inhibition capabilities. The impact of several common agents as well pH, on NexoBrid® debridement efficiency was evaluated in vitro. A collagen-based dermal substitute (MatriDerm®) was exposed to NexoBrid® in the presence of different agents of varying concentrations. Digestion was documented. The criteria used for judging digestion were independently classified by 3 investigators at least 3 times in succession. When a low concentration (1.0 mg/ml) of NexoBrid® was used, a ≥ 50% concentration of Prontosan® had an impact on enzymatic activity. Comparable results were obtained when even lower concentrations of Octenisept® (≥ 10%) were used. A 100-µmol/L concentration of copper inhibited the enzymatic activity of both a low (1.0 mg/ml) and high (10 mg/ml) concentration of NexoBrid®. Silver-sulfadiazine at concentrations of 10% and 90% inhibited the activity of 1 mg/ml NexoBrid®. No complete inhibition of NexoBrid® activity occurred at any concentration of iron. We recommend using polyhexanide-containing agents (Prontosan®) to rinse and presoak burn wounds. Pretreatment of burn wounds with agents containing silver and copper should be avoided. Experimentally, we found a partial inhibition of NexoBrid® activity at the distinct pH values of 3 and 11.

Fungicidal PMMA-Undecylenic Acid Composites.

Undecylenic acid (UA), known as antifungal agent, still cannot be used to efficiently modify commercial dental materials in such a way that this affects Candida. Actually, issues with Candida infections and fungal resistance compromise the use of Poly(methyl-methacrylate) (PMMA) as dental material. The challenge remains to turn PMMA into an antifugal material, which can ideally affect both sessile (attached) and planktonic (free-floating) Candida cells. We aimed to tackle this challenge by designing PMMA-UA composites with different UA concentrations (3-12%). We studied their physico-chemical properties, the antifungal effect on Candida and the cytotoxicity toward human cells. We found that UA changes the PMMA surface into a more hydrophilic one. Mainly, as-preparation composites with ≥6% UA reduced sessile Candida for >90%. After six days, the composites were still efficiently reducing the sessile Candida cells (for ~70% for composites with ≥6% UA). Similar results were recorded for planktonic Candida. Moreover, the inhibition zone increased along with the UA concentration. The antifungal effect of UA was also examined at the surface of an UA-loaded agar and the minimal inhibitory concentration (MIC90) was below the lowest-studied 0.0125% UA. Furthermore, the embedded filamentation test after 24 h and 48 h showed complete inhibition of the Candida growth at 0.4% UA.

ω-hydroxyundec-9-enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines.

ω-Hydroxyundec-9-enoic acid (ω-HUA), a plant secondary metabolite, exhibits anti-fungal activity. However, its effect on breast cancer cells is unknown. Here, we investigated the anti- breast cancer activity of ω-HUA and its underlying mechanism. Treatment of human breast cancer cell lines, MDA-MB-231 and MDA-MB-435, with ω-HUA induced apoptotic cell death with increased cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels, and p38 and JNK phosphorylation. Inhibition of these mitogen-activated protein kinase (MAPK) pathways using specific inhibitors or siRNA, for p38 and JNK, respectively, blocked the ω-HUA-induced apoptosis in a dose-dependent manner. Moreover, pretreatment of the cells with antioxidant N-acetyl cysteine (NAC) inhibited ω-HUA-induced increased reactive oxygen species (ROS) levels, cleaved caspase-3 and cleaved PARP, and phosphorylated JNK, phosphorylated p38, and increased cell viability and colony-forming ability. MDA-MB-231 xenograft model showed that the ω-HUA-treated group exhibited greater tumor regression and significantly reduced tumor weight compared to that exhibited by the vehicle-administered group. Collectively, ω-HUA-induced intracellular ROS generation induced breast cancer cell apoptosis through JNK and p38 signaling pathway activation, resulting in tumor regression. The results suggested that ω-HUA is an effective supplement for inhibiting human breast cancer growth.

Undec-10-enoic acid functionalized chitosan based novel nano-conjugate: An enhanced anti-bacterial/biofilm and anti-cancer potential.

Fatty acid functionalized chitosan conjugates are of great interest in cancer therapeutics because of its internalization through receptor mediated endocytosis into the cancer cells. Keeping the above fact into consideration, herein we synthesized the undec-10-enoic acid functionalized chitosan based undecyl-chitosan (U-CS) nano-bioconjugate with the use of DCC as a coupling agent. The U-CS conjugate synthesized was confirmed and characterized by FTIR, 1H NMR, TGA, XRD, SEM and TEM analysis. Generally, it is well established that conjugates of oleic acid with human Alpha-lactalbumin (HAMLET) induce cytotoxicity in the altered cells, but not in healthy cells. To check our presumptions, anti-bacterial and anti-cancer potential of U-CS was evaluated against bacterial pathogens (Gram +ve and Gram -ve) and human cancer cell lines (HeLa, MDA-MB-231 and Hep3B). The results of our study clearly revealed that conjugate showed enhance anti-bacterial, anti-biofilm as well as anti-cancer efficacy as compared to pure and free form of the chitosan.

In vitro and in vivo assessment of heart-homing porous silicon nanoparticles.

Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 µg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [(111)In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.

Polyelectrolyte-coated nanocapsules containing undecylenic acid: Synthesis, biocompatibility and neuroprotective properties.

The main objectives of the present study were to investigate the biocompatibility of polyelectrolyte-coated nanocapsules and to evaluate the neuroprotective action of the nanoencapsulated water-insoluble neuroprotective drug-undecylenic acid (UDA), in vitro. Core-shell nanocapsules were synthesized using nanoemulsification and the layer-by-layer (LbL) technique (by saturation method). The average size of synthesized nanocapsules was around 80 nm and the concentration was 2.5 × 10(10) particles/ml. Their zeta potential values ranged from less than -30 mV for the ones with external polyanion layers through -4 mV for the PEG-ylated layers to more than 30 mV for the polycation layers. Biocompatibility of synthesized nanocarriers was evaluated in the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). The results obtained showed that synthesized nanocapsules coated with PLL and PGA (also PEG-ylated) were non-toxic to SH-SY5Y cells, therefore, they were used as nanocarriers for UDA. Moreover, studies with ROD/FITC-labeled polyelectrolytes demonstrated approximately 20% cellular uptake of synthetized nanocapsules. Further studies showed that nanoencapsulated form of UDA was biocompatible and protected SH-SY5Y cells against the staurosporine-induced damage in lower concentrations than those of the same drug added directly to the culture medium. These data suggest that designed nanocapsules might serve as novel, promising delivery systems for neuroprotective agents.

An Involvement of PI3-K/Akt Activation and Inhibition of AIF Translocation in Neuroprotective Effects of Undecylenic Acid (UDA) Against Pro-Apoptotic Factors-Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells.

Undecylenic acid (UDA), a naturally occurring 11-carbon unsaturated fatty acid, has been used for several years as an economical antifungal agent and a nutritional supplement. Recently, the potential usefulness of UDA as a neuroprotective drug has been suggested based on the ability of this agent to inhibit µ-calpain activity. In order to verify neuroprotective potential of UDA, we tested protective efficacy of this compound against cell damage evoked by pro-apoptotic factors (staurosporine and doxorubicin) and oxidative stress (hydrogen peroxide) in human neuroblastoma SH-SY5Y cells. We showed that UDA partially protected SH-SY5Y cells against the staurosporine- and doxorubicin-evoked cell death; however, this effect was not connected with its influence on caspase-3 activity. UDA decreased the St-induced changes in mitochondrial and cytosolic AIF level, whereas in Dox-model it affected only the cytosolic AIF content. Moreover, UDA (1-40 µM) decreased the hydrogen peroxide-induced cell damage which was connected with attenuation of hydrogen peroxide-mediated necrotic (PI staining, ADP/ATP ratio) and apoptotic (mitochondrial membrane potential, caspase-3 activation, AIF translocation) changes. Finally, we demonstrated that an inhibitor of PI3-K/Akt (LY294002) but not MAPK/ERK1/2 (U0126) pathway blocked the protection mediated by UDA in all tested models of SH-SY5Y cell injury. These in vitro data point to UDA as potentially effective neuroprotectant the utility of which should be further validated in animal studies.

Fast determination of multiple-reaction intermediates for long-chain dicarboxylic Acid biotransformation by gas chromatography-flame ionization detector.

For the analysis of multiple-reaction intermediates for long-chain dicarboxylic acid biotransformation, simple and reproducible methods of extraction and derivatization were developed on the basis of gas chromatography with flame ionization detector (GC-FID) instead of mass spectrometry. In the derivatization step, change of the ratio of pyridine to MSTFA from 1:3 to 9:1 resulted in higher peak intensity (p = 0.021) and reproducibility (0.6%CV) when analyzing 32 g/l ricinoleic acid (RA). Extraction of RA and ω-hydroxyundec- 9-enoic acid with water containing 100 mM Tween 80 showed 90.4-99.9% relative extraction efficiency and 2-7%CV compared with those with hydrophobic ethyl acetate. In conclusion, reduction of the pyridine content and change of the extraction solvent to water with Tween 80 provided compatible derivatization and extraction methods to GC-FID-based analysis of longchain carboxylic acids.

Validación de los métodos para control de calidad de los ingredientes activos en Fungirex crema / Validation of the quality control methods for active ingredients of Fungirex cream

INTRODUCCIÓN: Fungirex crema es un producto que contiene dos fármacos: ácido undecilénico y undecilenato de zinc en una base adecuada. Como se trata de un producto que no aparece en las monografías oficiales de las farmacopeas, se proponen métodos analíticos sencillos capaces de cuantificar los analitos de interés en la crema, útiles para la liberación de los lotes de crema recién elaborados. OBJETIVO: validar dos métodos volumétricos para control de calidad de los ingredientes activos presentes en Fungirex crema. MÉTODOS: se propuso una volumetría de neutralización directa para cuantificar ácido undecilénico previa extracción del analito y la complejometría con EDTA para undecilenato de zinc. Atendiendo a la clasificación de ambos métodos en la categoría I, se realizó la validación de ambos métodos a través de los parámetros: especificidad, linealidad, exactitud, precisión y rango. RESULTADOS: se corroboró la ausencia de interferencia de los restantes componentes de la matriz. Los criterios de aceptación establecidos para linealidad, exactitud y precisión se cumplieron satisfactoriamente para los dos métodos en estudio, por lo que fueron válidos en el rango de 50 a 150 por ciento (método por volumetría de neutralización: 25,6-76,8 mg/g y método por complejometría: 111,1-333,3 mg/g). CONCLUSIONES: los métodos volumétricos propuestos fueron lineales, precisos, exactos y específicos para realizar el control de calidad de Fungirex crema en base al contenido de ácido undecilénico y undecilenato de zinc(AU)

INTRODUCTION: Fungirex cream is a two-drug product, that is, undecylenic acid and zinc undecylenate over a suitable basis. Since this is a product not documented in the official monographs of the pharmacopeae, simple analytical methods were suggested for quantitation of analytes of interest in the cream, which are useful for release of newly prepared cream batches. OBJECTIVE: to validate two volumetric methods for the quality control of active ingredients in Fungirex cream. METHODS: a direct neutralization volumetric method was suggested to quantitate undecylenic acid after the analyte extraction and EDTA complexometry for zinc undecylenate . According to the classification of both methods in the category I, they were validated through the parameters specificity, linearity, accuracy, precision and range. RESULTS: the non-interference of the rest of the matrix components was corroborated. The set acceptance criteria for linearity, accuracy and precision were satisfactorily met for the two study methods, so they were valid in the 50-150 percent range (neutralization volumetry method: 25.6-76.8 mg/g and complexometry method 111.1-333,3 mg/g). CONCLUSIONS: the suggested volumetric methods were linear, specific, precise, and accurate for the quality control of Fungirex cream based on the undecylenic acid and zinc undecylenate content(AU)

ω-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells.

ω-Hydroxyundec-9-enoic acid (ω-HUA), a hydroxyl unsaturated fatty acid derivative, is involved in the antifungal activity of wild rice (Oryza officinalis). Here, we investigated the anti-cancer activity of ω-HUA on a non-small cell lung cancer (NSCLC) cell line. ω-HUA increased apoptosis and induced cleavages of caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP). ω-HUA treatment significantly induced endoplasmic reticulum (ER) stress response. Suppression of CHOP expression and inhibiting ER stress by 4-phenylbutyrate (4-PBA) significantly attenuated the ω-HUA treatment-induced activation of caspase-6, caspase-9, and PARP, and subsequent apoptotic cell death, indicating a role for ER stress in ω-HUA-induced apoptosis. In addition, cells subjected to ω-HUA exhibited significantly increased quantity of reactive oxygen species (ROS), and the ROS scavenger N-acetyl-L-cysteine (NAC) inhibited ω-HUA-induced apoptotic cell death and ER stress signals, indicating a role for ROS in ER stress-mediated apoptosis in ω-HUA-treated cells. Taken together, these results suggest that sequential ROS generation and ER stress activation are critical in ω-HUA treatment-induced apoptosis and that ω-HUA represents a promising candidate for NSCLC treatment.

Antimicrobial polyurethane thermosets based on undecylenic acid: synthesis and evaluation.

In the present study, plant oil-derived surface-modifiable polyurethane thermosets are presented. Polyol synthesis is carried out taking advantage of thiol-yne photopolymerization of undecylenic acid derivatives containing methyl ester or hydroxyl moieties. The prepared methyl ester-containing polyurethanes allow surface modification treatment to enhance their hydrophilicity and impart antimicrobial activity through the following two steps: i) grafting poly(propylene glycol) monoamine (Jeffamine M-600) via aminolysis and ii) Jeffamine M-600 layer complexation with iodine. The antimicrobial activity of the iodine-containing polyurethanes is demonstrated by its capacity to inhibit the growth of Staphylococcus aureus, and Candida albicans in agar media.

Enhancement of fatty acid-based polyurethanes cytocompatibility by non-covalent anchoring of chondroitin sulfate.

For tissue engineering purpose biopolymer chondroitin sulfate (CS), one of the major components of cartilage and bone extracellular matrix, was immobilized onto the surface of amino-functionalized polyurethane (PU) films derived from naturally occurring oleic and 10-undecenoic acids. The amino-functionalized PUs were prepared by aminolysis with 1,6-hexamethylenediamine of synthesized PUs containing methyl ester groups. FTIR-ATR, XPS, SEM, and water contact angle measurements were used to confirm the surface changes at each step of treatment, both in morphologies and chemical composition. Cytotoxicity and cell morphology analysis using osteoblast cell line MG63 showed that PU-CS films are suitable materials for cell growth, spreading, and differentiation.

Functionalized mesoporous silicon for targeted-drug-delivery.

The present work concerns a preliminary step in the production of anticancer drug loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful procedure for the covalent attachment of folic acid, polyethylene glycol (PEG) and doxorubicin to hydrophilic mesoporous silicon layers is presented. A systematic approach has been followed to obtain the optimal composition of the N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide (DMSO) solution for the surface activation process of the undecylenic acid (UD) grafted molecules to take place with minimal undesired byproduct formation. The effect of reactant concentration and kind of solvent (aqueous or DMSO) on the attachment of folic acid to the activated PSi layer has been investigated. The covalent attachment of the doxorubicin molecules to the PSi layer functionalized with folic acid and PEG is discussed. The drug release kinetics as a function of pH has been studied. The functionalized PSi particles show a high cytotoxicity compared to the equivalent amount of free drug. Cell toxicity tests show clearly that the incorporation of folate molecules increases substantially the toxicity of the loaded PSi particles. Accordingly this new functionalized PSi may be considered a proper candidate for targeted drug delivery.