Simultaneous Grafting Polymerization of Acrylic Acid and Silver Aggregates Formation by Direct Reduction Using γ Radiation onto Silicone Surface and Their Antimicrobial Activity and Biocompatibility.

The modification of medical devices is an area that has attracted a lot of attention in recent years; particularly, those developments which search to modify existing devices to render them antimicrobial. Most of these modifications involve at least two stages (modification of the base material with a polymer graft and immobilization of an antimicrobial agent) which are both time-consuming and complicate synthetic procedures; therefore, as an improvement, this project sought to produce antimicrobial silicone (PDMS) in a single step. Using gamma radiation as both an energy source for polymerization initiation and as a source of reducing agents in solution, PDMS was simultaneously grafted with acrylic acid and ethylene glycol dimethacrylate (AAc:EGDMA) while producing antimicrobial silver nanoparticles (AgNPs) onto the surface of the material. To obtain reproducible materials, experimental variables such as the effect of the dose, the intensity of radiation, and the concentration of the silver salt were evaluated, finding the optimal reaction conditions to obtain materials with valuable properties. The characterization of the material was performed using electronic microscopy and spectroscopic techniques such as 13C-CPMAS-SS-NMR and FTIR. Finally, these materials demonstrated good antimicrobial activity against S. aureus while retaining good cell viabilities (above 90%) for fibroblasts BALB/3T3.

Physicochemical stability of bioadhesive thermoresponsive platforms for methylene blue and hypericin delivery in photodynamic therapy.

Hypericin (Hyp), a natural hydrophobic and photoactive pigment, and methylene blue (MB), a hydrophilic cationic dye, are utilized as photosensitizer (PS) for photodynamic therapy of cancer. Bioadhesive and thermoresponsive polymeric systems can improve the drug availability by increasing the contact time between the system and the mucosa and also controlling the drug release. In this work, an accelerated physicochemical stability study of binary polymeric systems composed of poloxamer 407 (Polox) and Carbopol 934 P (Carb) for MB or Hyp release was performed. Formulations were prepared containing Polox (20%, w/w), Carb (0.15%, w/w) and MB (0.25%, w/w) or Hyp (0.01%, W/W) and submitted to different stress conditions (5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C with relative humidity of 75 ± 5%) during 180 days. The samples were analyzed as macroscopic characteristics, photosensitizer content and mechanical properties by texture profile analysis. Both systems displayed decrease of photosensitizer content less than 5% during 180 days. MB-system showed an undefined reaction model, while Hyp-system displayed PS decay following a pseudo first-order reaction. Systems also displayed stable mechanical characteristics. The pharmaceutical analyses showed the good physicochemical stability of the bioadhesive platform for delivery Hyp and MB in photodynamic therapy.

Effect of the combination of a crosslinking agent and a thiourethane additive on the properties of acrylic denture bases processed with microwave energy.

Thiourethane (TU) additives and difunctional, polymerizable crosslinking agents have been demonstrated to increase toughness in methacrylate-based materials. The aim of this study was to evaluate the potential reinforcement of acrylic denture bases by combining thiourethane additives and 1,6 hexanediol dimethacrylate (HDDMA) as an additional crosslinking agent. One commercial acrylic resin (Nature-Cryl MC; GC America) was tested by adding 0 (control) or 10 wt% TU, each of them combined with 0 (control), 10, 20 and 30 wt% HDDMA, for a total of 8 experimental groups. Materials were processed using microwave energy (500 W for 3 min) using microwave-safe molds and flasks. Flexural strength, modulus and toughness were obtained in 3-point bending (ISO 4049) using bars measuring 2 × 2x25 mm (n = 6). Dynamic mechanical analysis was used to determine glass transition temperature (Tg), breadth of tan delta (as a measure of polymer heterogeneity) and crosslinking density in 1 × 3x15 mm bars (n = 6) tested in tension, using a 3 °C/min heating rate (-30 to 180 °C). Viscosity samples were evaluated in a parallel plate reometer. Data were analyzed by two-way ANOVA and Tukey's test (α = 0.05). Results showed that on the samples not containing TU, HDDMA up to 20 wt% increased the flexural strength and thoughness (and up to 30 wt% HDDMA increased the modulus). The addition of TU did not affect those properties (except for the increase in elastic modulus), but the combination TU + HDDMA led to decreased properties overall. The addition of HDDMA decreased the viscosity for all materials, and the presence of TU did not affect viscosity. The Tg increased linearly with the concentration of HDDMA, except in the groups containing TU - in general, the addition of TU reduced Tg. The crosslinking density increased with the addition of HDDMA for all materials, regardless of the presence of TU. The addition of TU significantly decreased crosslinking density. The breadth of tan delta was not affected by the addition of HDDMA, but significantly increased with the addition of TU. In conclusion, the chain-breaking effect of TU on polymerizing methacrylates was deleterious in the case of methyl methacrylate, since it forms a linear polymer. The addition of HDDMA up to 20 wt% and not combined with TU significantly improved the tested properties.

Evaluation of the Antimicrobial Activity of Cationic Peptides Loaded in Surface-Modified Nanoliposomes against Foodborne Bacteria.

Bacteria are a common group of foodborne pathogens presenting public health issues with a large economic burden for the food industry. Our work focused on a solution to this problem by evaluating antibiotic activity against two bacteria (Listeria monocytogenes and Escherichia coli) of relevance in the field of foodstuffs. We used two approaches: (i) structural modification of the antimicrobial peptides and (ii) nano-vehiculisation of the modified peptides into polymer-coated liposomes. To achieve this, two antimicrobial peptides, herein named 'peptide +2' and 'peptide +5' were synthesised using the solid phase method. The physicochemical characterisation of the peptides was carried out using measurements of surface tension and dynamic light scattering. Additionally, nanoliposomes were elaborated by the ethanol injection method and coated with a cationic polymer (Eudragit E-100) through the layer-by-layer process. Liposome characterisation, in terms of size, polydispersity and zeta potential, was undertaken using dynamic light scattering. The results show that the degree of hydrophilic modification in the peptide leads to different characteristics of amphipathicity and subsequently to different physicochemical behaviour. On the other hand, antibacterial activity against both bacteria was slightly altered after modifying peptide sequence. Nonetheless, after the encapsulation of the peptides into polymer-coated nano-liposomes, the antibacterial activity increased approximately 2000-fold against that of L. monocytogenes.

Polysaccharide-based hydrogels for the immobilization and controlled release of bovine serum albumin.

Arabic gum-based and chitosan-based hydrogels were synthesized through chemical crosslinking for the immobilization and controlled release of bovine serum albumin (BSA) and characterized by Fourier-transform infrared spectrometry, scanning electron microscopy and swelling assays. The degrees of swelling of the Arabic gum-based hydrogel were 13.22 and 22.95 g water per g dried hydrogel at pH 4.5 and 7.0, respectively, whereas the degrees of swelling of the chitosan-based hydrogel were 15.32 and 36.10 g water per g dried hydrogel, respectively. The water absorption mechanism in both hydrogels was non-Fickian, which involves diffusion through pores and macromolecular relaxation of the hydrophilic three-dimensional polymer network. BSA immobilization capacities of the Arabic gum-based and chitosan-based hydrogels after 240 min at pH 4.5 were 71.0 and 175.6 mg protein per g dried hydrogel, respectively. BSA immobilization capacities after 240 min at pH 7.0 were 62.5 and 154.2 mg protein per g dried hydrogel, respectively. The controlled release of BSA from the Arabic gum-based hydrogel was slightly more efficient than that of the chitosan-based hydrogel due to its more porous structure and weaker physiochemical interactions between the polymer network and protein molecule. Both hydrogels could be employed as carriers of proteins and as capsules for food supplements.

Antimicrobial peptide-loaded liquid crystalline precursor bioadhesive system for the prevention of dental caries.

BACKGROUND: Anticaries agents must interfere with the adhesion of Streptococcus mutans and its proliferation in dental biofilm, without causing host toxicity and bacterial resistance. Natural substances, including cationic antimicrobial peptides (CAMPs) and their fragments, such as ß-defensin-3 peptide fragment (D1-23), have been widely studied. However, the chemical and physical stability of CAMPs may be compromised by external factors, such as temperature and pH, reducing the period of antimicrobial activity. METHODS: To overcome the aforementioned disadvantage, this study developed and character-ized a drug delivery system and evaluated the cytotoxicity and effect against S. mutans biofilm of a D1-23-loaded bioadhesive liquid crystalline system (LCS). LCS was composed of oleic acid, polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, Carbopol® 974P and Carbopol® 971P. LCS was analyzed by polarized light microscopy (PLM), rheology (viscoelasticity and flow properties) and in vitro bioadhesion. The viability of epithelial cells was evaluated. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against S. mutans were determined for D1-23 for further evaluation of the effect against S. mutans biofilm after 4 and 24 h of exposure to treatments. RESULTS: PLM, rheology, and in vitro bioadhesion tests showed that both viscosity and bioadhesion of LCS increased after it was diluted with artificial saliva. D1-23-loaded LCS system presented better activity against S. mutans biofilm after 24 h when compared to 4 h of treatment, showing a cumulative effect. Neither LCS nor D1-23-loaded LCS presented toxicity on human epithelial cells. CONCLUSION: D1-23-loaded LCS is a promising drug delivery system for the prevention of dental caries.

Optimization of antimalarial, and anticancer activities of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate.

Chemically modified versions of bioactive substances, are particularly useful in overcoming barriers associated with drug formulation, drug delivery and poor pharmacokinetic properties. In this study, a series of fourteen (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (2-15) were prepared by using a one step synthesis from 1 previously described by us as potential antimalarial and antitumor agent. Molecules were evaluated as inhibitors of ß-hematin formation, where most of them showed a significant inhibition value (% > 70). The best inhibitors were tested in vivo as potential antimalarials in mice infected with P. berghei ANKA, chloroquine susceptible strain. Three of them (5, 6, and 15) displayed antimalarial activity comparable to that of chloroquine. Also, molecules were evaluated for their cytotoxic activity against two human cancer cell lines (Jurkat E6.1 and HL60) and primary culture of human lymphocytes. Most of the synthesized compounds, except for analogs 2-6, 8, and 10-12, displayed cytotoxicity against cancer cell lines without affecting normal cells. The potency of the compounds was 15 ≫ 1, and 14 > 7, 9, and 13. Flow cytometry analysis demonstrated an increase in apoptotic cell death after 24 h. The compounds may affect tumor cell autophagy and consequently increase cell apoptosis.

Synthesis and characterization of poly(N-vinylcaprolactam)-based spray-dried microparticles exhibiting temperature and pH-sensitive properties for controlled release of ketoprofen.

Poly(N-vinylcaprolactam) (PNVCL) and poly(N-vinylcaprolactam-co-acrylic acid) (poly(NVCL-co-AA)) were synthesized by solution-free radical polymerization and displayed thermo-responsive behavior, with lower critical solution temperatures (LCSTs) of 35 °C and 39 °C, respectively. The incorporation of AA unities made the poly(NVCL-co-AA) sensitive to both pH and temperature. They were exploited in this work in preparing microparticles loaded with ketoprofen via spray-drying to modulate the drug release rate by changing pH or temperature. The interaction between polymer and drug was studied using X-ray diffractometry, Raman spectrometry and scanning electron microscopy (SEM). The biocompatibility of pure polymers, free ketoprofen as well as the spray-dried particles was demonstrated in vitro by low cytotoxicity and a lack of nitric oxide production in macrophages at concentrations as high as 100 µg/ml. The release profile of ketoprofen was evaluated by in vitro assays at different temperatures and pH values. Drug diffusion out of PNVCL's hydrated polymer network is increased at temperatures below the LCST. However, when poly(NVCL-co-AA) was used as the matrix, the release of ketoprofen was primarily controlled by the pH of the medium. These results indicated that PNVCL and the novel poly(NVCL-co-AA) could be promising candidates for pH and temperature-responsive drug delivery systems.

Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease.

A novel series of feruloyl-donepezil hybrid compounds were designed, synthesized and evaluated as multitarget drug candidates for the treatment of Alzheimer's Disease (AD). In vitro results revealed potent acetylcholinesterase (AChE) inhibitory activity for some of these compounds and all of them showed moderate antioxidant properties. Compounds 12a, 12b and 12c were the most potent AChE inhibitors, highlighting 12a with IC50 = 0.46 µM. In addition, these three most promising compounds exhibited significant in vivo anti-inflammatory activity in the mice paw edema, pleurisy and formalin-induced hyperalgesy models, in vitro metal chelator activity for Cu2+ and Fe2+, and neuroprotection of human neuronal cells against oxidative damage. Molecular docking studies corroborated the in vitro inhibitory mode of interaction of these active compounds on AChE. Based on these data, compound 12a was identified as a novel promising drug prototype candidate for the treatment of AD with innovative structural feature and multitarget effects.

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita-Baylis-Hillman Adducts: In Vitro Screening against Leishmania donovani.

Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita-Baylis-Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/antiinflammatory tetrahydropyrans derivatives and Morita-Baylis-Hillman adducts. First, acrylates were synthesized from analgesic/anti-inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70-75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60-95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC50), 50% hemolysis concentration (HC50), selectivity index (HC50/IC50,), and comparing to Amphotericin B, chosen as the anti-leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SIrb > 180.19), compared with the highly-toxic reference drug (SIrb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies.

Synthesis and In Vitro Anti Leishmania amazonensis Biological Screening of Morita-Baylis-Hillman Adducts Prepared from Eugenol, Thymol and Carvacrol.

Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC50 values in the range of 22.30-4.71 µM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime® (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism.

Selective solid-phase extraction using molecularly imprinted polymers for analysis of venlafaxine, O-desmethylvenlafaxine, and N-desmethylvenlafaxine in plasma samples by liquid chromatography-tandem mass spectrometry.

This paper focuses on the development of a novel miniaturized molecularly imprinted solid-phase extraction (MISPE) and ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine venlafaxine (VEN), O-desmethylvenlafaxine (ODV), and N-desmethylvenlafaxine (NDV) in plasma samples. The molecularly imprinted polymer (MIP) was prepared by the precipitation polymerization approach; VEN, metacrylic acid, ethylene glycol dimethacrylate, 2,2-azobisisobutyronitrile, and toluene were used as template, monomer, crosslinker, initiator, and porogen solvent, respectively. MIP and of the non-imprinted control polymer (NIP) sorbents were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. MIP phase presented higher extraction efficiency (MISPE, using plasma samples spiked with VEN) than the NIP phase (84 and 49% recovery rates, respectively). Analysis of other antidepressants with different chemical structures by MISPE-UHPLC-MS/MS attested to the selectivity of the developed MIP. The developed method presented precision assays with coefficients of variation (CV) smaller than 15%; accuracy assays with relative standard error (RSE%) values ranging from -12 to 16%, and linear ranges from 3 to 700ngmL(-1) for VEN, from 5 to 700ngmL(-1) for ODV, and from 3 to 500ngmL(-1) for NDV. The coefficients of determination (r(2)) were higher than 0.995. The lack-of-fit test also attested to the linearity of this method. This method was successfully applied to determine VEN, NDV, and ODV in plasma samples from depressed patients undergoing therapy with VEN.

Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies.

Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect.

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3µm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects.

Formulation and Evaluation of a Mucoadhesive Thermoresponsive System Containing Brazilian Green Propolis for the Treatment of Lesions Caused by Herpes Simplex Type I.

The aim of the present work was to develop a topical delivery system that contains Brazilian green propolis extract (PE-8) to increase efficiency and convenience when applied to herpetic lesions. The cytotoxicity and antiherpetic activity was determined in vitro and in vivo. The PE-8 was added to a system that contained poloxamer 407 and carbopol 934P. The in vitro characterization of the system included rheological studies, texture profile analysis, and mucoadhesion analysis. The PE-8 inhibited the virus during the phase of viral infection, induced virion damage, and exhibited an ability to protect cells from viral infection. The system had advantageous mucoadhesive properties, including a suitable gelation temperature of approximately 25°C for topical delivery, a desirable textural profile, and pseudoplastic behavior. The in vitro release study showed a rapid initial release of the PE-8 in the first 3 h, and the rate of drug release remained constant for up to 24 h. The system appeared to be macroscopically and microscopically innocuous to skin tissue. Therefore, the mucoadhesive thermoresponsive system that contained the PE-8 appears to be promising for increasing bioavailability and achieving prolonged release of the PE-8 when applied to skin lesions caused by herpes simplex virus type 1.

Effect of denture-coating composite on Candida albicans biofilm and surface degradation after disinfection protocol.

INTRODUCTION: Denture stomatitis is the most common pathology affecting denture wearers and its main cause is colonisation of dentures with Candida albicans. OBJECTIVE: This study investigated the effectiveness of two commercial composite surface sealants (Biscover(®) LV and Surface Coat(®)) to reduce C. albicans biofilm colonisation on denture resin, as well as their surface integrity after disinfection cycles with 1% sodium hypochlorite solution. METHODS: Heat-cured acrylic resin specimens were manufactured (10 mm × 10 mm × 1 mm). The specimen surfaces were mechanically polished to simulate rough or smooth denture surfaces. Four surface-treatment groups were tested: smooth surfaces [0.3 µm of mean roughness (Ra)]; rough surfaces (3 µm of Ra); rough surfaces treated with Biscover(®) LV; and rough surfaces treated with Surface Coat(®). Specimens of each group were randomly divided to undergo immersion in distilled water or 1% sodium hypochlorite for 30 or 90 cycles each. Specimens of all groups in each immersion solution were tested using a crystal violet (CV) staining assay for biofilm quantification and by scanning electron microscopy for visual analyses of surface integrity and biofilm structure. CV assay data were analysed using one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test (P < 0.05). RESULTS: The effectiveness and surface integrity of Biscover(®) LV-treated surfaces were similar to those of smooth surfaces, whereas Surface Coat(®) -treated surfaces presented a similar performance to rough surfaces in all solutions and cycles. CONCLUSION: These results suggest the possibility of clinical use of Biscover(®) LV for denture coating on surfaces in which mechanical polish is not indicated, such as the fitting surface.

Screening and In Vitro Evaluation of Mucoadhesive Thermoresponsive System Containing Methylene Blue for Local Photodynamic Therapy of Colorectal Cancer.

PURPOSE: Photodynamic therapy (PDT) with methylene blue (MB) constitutes a potentially useful modality for colorectal cancer treatment. The limitations of the formulations containing MB are problems of administration and the inability to get the closeness contact at the site during the appropriate residence time. Present study aimed to develop and characterize mucoadhesive thermoresponsive system containing MB designed as platform for colorectal cancer therapy. METHODS: Formulations composed of different amounts of poloxamer 407 (Polox), Carbopol 934P (Carb), and MB were developed and characterized as rheological, compressional, mucoadhesive and syringeability properties, toxicity, photodynamic action, in vitro MB release profile, and ex vivo MB intestinal permeation. RESULTS: The different compositions resulted in formulations with distinctive macroscopic characteristics and wide range of gelation temperatures. The compressional flow, mucoadhesive, syringeability, and rheological properties were significantly influenced by temperature and/or composition. The MB release from formulation was governed by anomalous transport. In addition, it was observed that MB permeated the intestinal membrane; the formulation possesses photodynamic activity and low toxicity. CONCLUSIONS: The data obtained from the system composed of 20% Polox, 0.15% Carb, and 0.25% MB indicated a potentially functional role in PDT of the colorectal cancer and suggest it is worthy of clinical evaluation.

Oleanolic acid acrylate elicits antidepressant-like effect mediated by 5-HT1A receptor.

The development of new drugs for the treatment of depression is strategic to achieving clinical needs of patients. This study evaluates antidepressant-like effect and neural mechanisms of four oleanolic acid derivatives i.e. acrylate (D1), methacrylate (D2), methyl fumarate (D3) and ethyl fumarate (D4). All derivatives were obtained by simple one-step esterification of oleanolic acid prior to pharmacological screening in the forced swimming (FS) and open field (OF) tests. Pharmacological tools like α-methyl-p-tyrosine (AMPT, catecholamine depletor), p-chlorophenylalanine (serotonin depletor), prazosin (PRAZ, selective α1-receptor antagonist), WAY-100635 (selective serotonin 5-HT1A receptor antagonist) as well as monoamine oxidase (MAO) and functional binding assays were conducted to investigate possible neural mechanisms. In the FS test, D1 showed the most promising antidepressant-like effect without eliciting locomotor incoordination. Unlike group of mice pretreated with AMPT 100 mg/kg, PCPA 100 mg/kg or PRAZ 1 mg/kg, the effect of D1 was attenuated by WAY-100635 0.3 mg/kg pretreatment. D1 demonstrated moderate inhibition of MAO-A (IC50 = 48.848 ± 1.935 µM), potency (pEC50 = 6.1 ± 0.1) and intrinsic activity (E max = 26 ± 2.0%) on 5-HT1A receptor. In conclusion, our findings showed antidepressant-like effect of D1 and possible involvement of 5-HT1A receptor.

Singly and binary grafted poly(vinyl chloride) urinary catheters that elute ciprofloxacin and prevent bacteria adhesion.

Acrylic acid (AAc) and poly(ethylene glycol) methacrylate (PEGMA) were singly and dually grafted onto poly(vinyl chloride) (PVC) urinary catheters with the aim of preventing biofouling by endowing the catheters with the ability to load and release antimicrobial agents and to avoid bacteria adhesion. The polymers were grafted applying an oxidative pre-irradiation ((60)Co source) method in two steps. Grafting percentage and kinetics were evaluated by varying the absorbed pre-irradiation dose, reaction time, monomer concentration, and reaction temperature. Catheters with grafting percentages ranging from 8 to 207% were characterized regarding thermal stability, surface hydrophilicity, mechanical properties, swelling, and lubricity. The modified catheters proved to have better compatibility with fibroblast cells than PVC after long exposure times. Furthermore, grafted catheters were able to load ciprofloxacin and sustained its release in urine medium for several hours. Ciprofloxacin-loaded catheters inhibited the growth of Escherichia coli and Staphylococcus aureus in the catheter surroundings and prevented bacteria adhesion.

Novel poly(NIPA-co-AAc) functional hydrogels with potential application in drug controlled release.

The synthesis, characterization and properties of pH/thermosensitive hydrogels based on acrylic acid (AAc) and N-isopropylacrylamide (NIPA) using (+)-N,N'-diallyltartramide (DAT) as cross-linking agent and water as solvent, are presented in this article. Subsequently, the incorporation of ofloxacin (OFL) as model drug to evaluate the drug load capacity of hydrogels and the in vitro release from OFL-polymer conjugate are presented in order to define potential pharmaceutical applications. Interestingly, the incorporation of AAc diversified the properties of NIPA-based hydrogels allowing ionic interaction of these new materials with drugs of opposite charge and produced different release profiles at pH 1.2 and 6.8 simulated physiological media.