Liliana Tartau

Exposure to silver nanoparticles induces oxidative stress and memory deficits in laboratory rats

Currently most of the applications of silver nanoparticles are in antibacterial/antifungal agents in medicine and biotechnology, textile engineering, water treatment and silver-based consumer products. However, the effects of silver nanoparticles on human body, especially on the central nervous system, are still unclear. To study the mechanisms underlying the effects of silverpoly(amidehydroxyurethane) coated silver nanoparticles on brain functions, we subjected male Wistar rats to chronic treatments with silver-29 nm (5 µg/kg and 10 µg/kg) and silver-23 nm (5 µg/kg and 10 µg/kg) nanoparticles for 7 days. We evaluated the effects of nanoparticles size and structure on rat memory function. Memory processes were studied by means of two cognitive tasks (Y-maze and radial arm-maze). Exposure to silver nanoparticles significantly decreased spontaneous alternation in the Y-maze task and working memory functions in the radial arm-maze task, suggesting that nanoparticles have effects on short-term memory. We found no effects on long-term memory, which we assessed by reference memory trials in the radial arm-maze task. We found that memory deficits were significantly correlated with oxidative stress generation only in the Y-maze task. Our findings suggest that silver nanoparticles may induce an impairment of memory functions by increasing oxidative stress in the brain. The use of silver nanoparticles for medical purposes therefore requires careful consideration, particularlyif it involves exposure of the human brain.

Attenuated effects of chitosan-capped gold nanoparticles on LPS-induced toxicity in laboratory rats

The impact of nanoparticles in medicine and biology has increased rapidly in recent years. Gold nanoparticles (AuNP) have advantageous properties such as chemical stability, high electron density and affinity to biomolecules. However, the effects of AuNP on human body after repeated administration are still unclear. Therefore, the purpose of the present study was to evaluate the effects of gold-11.68 nm (AuNP1, 9.8 μg) and gold-22.22 nm (AuNP2, 19.7 μg) nanoparticles capped with chitosan on brain and liver tissue reactivity in male Wistar rats exposed to lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, 250 μg) upon 8 daily sessions of intraperitoneal administration. Our results suggest that the smaller size of chitosan-capped AuNP shows the protective effects against LPS-induced toxicity, suggesting a very high potential for biomedical applications.

Upon synthesis of a polymeric matrix with pH and temperature responsiveness and antioxidant bioactivity based on poly(maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5] undecane) derivatives.

Poly(maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5] undecane), acquired through radical polymerization, was synthesized with the aim to prepare an alternant copolymer with precise placement of functional groups along the polymer backbones. The new structure owing to the suitable and specific functionalities is anticipated to be used as reactive polymer to link bioactive compounds via maleic anhydride moiety. The copolymer was improved in its functionality by maleic anhydride ring opening with different amounts of erythritol in order to confer antioxidant characteristics to the polymeric structure. The chemical structure of the new prepared polymers was confirmed by FTIR and (1)H NMR spectra, and the polymers were also characterized from the viewpoint of their thermal stability. The dual sensitivity of the polymeric structure, at temperature and pH, was evaluated by determining the hydrodynamic radius and zeta potential in interdependence with the environment conditions. The polymer morphology was investigated by SEM. The antioxidant character was evaluated measuring the scavenger properties of the functionalized copolymer with erythritol against the 2,2-diphenyl-1-picrylhydrazyl radicals. The acute toxicity investigation, realized in vivo for the copolymer and the derivatives, allows the inclusion of the compounds into the group of moderately toxic accordingly to Hodge and Sterner toxicity scale owing to the lethal dose 50 determined values.

Indomethacin uptake into poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2, 4,8,10-tetraoxaspiro (5.5)-undecane) network: In vitro and in vivo controlled release study

Networks based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane), synthesized through radical dispersion polymerization, were used as template for indomethacin (INN) as model drug. The copolymers were characterized by swelling studies at three pH values (2.4, 5.5 and 7.4) and two temperatures (room temperature 24 °C and physiological temperature 37 °C). Fourier transform infrared (FTIR) spectroscopic analysis was used to sustain the copolymer structures. Scanning electron microscopy (SEM) and thermogravimetric (TG) investigations were used to examine microstructure and appreciate the thermal stability of the polymer samples. The studies of the INN drug release from the copolymer networks were in vitro performed. The in vivo study results (biocompatibility tests, somatic nociceptive experimental model (tail flick test) and visceral nociceptive experimental model (writhing test)) are also reported in this paper.

Upon some multi-membrane hydrogels based on poly( N , N -dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) Undecane): preparation, characterization and in vivo tests

The study presents the possibility of preparation of multi-membrane gel systems with different morphologies and properties, based on poly(N,N-dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) copolymer and crosslinked with N,N′-methylene-bis-acrylamide. The basic copolymer has dual thermo- and pH sensitive character. After the core hydrogel is realized, the preformed gel is immersed in the aqueous solutions of ammonia, sodium chloride and sodium citrate for further edge constructing of the supramolecular assemblies. Then, the new layers by adding new sets of gelifying components are realized. The new multi-membrane gel systems are intended to be used as matrix for bioactive substances embedding. In this context the systems were loaded with norfloxacin as drug model. The in vivo tests show good biocompatibility for the implants based on multi-membrane gel structures loaded with drug.

Semi-imprinting Quercetin into Poly[N,N-Dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-Tetraoxaspiro (5.5) Undecane] Network: Evaluation of the Antioxidant Character

A responsive antioxidant system constituted from quercetin inserted into poly[N,N-dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane] through a semi-imprinted procedure was evaluated. A continuous magnetic field (MF) was used during supramolecular structure preparation. The strength of coupling quercetin was evaluated based on the template release from the polymeric matrices, as well as to what extent quercetin reloaded into the polymer matrix in prescribed conditions--with or without the MF presence--shows antioxidant properties. The antioxidant activity of the complex was investigated by radical inhibitor activity method using 2, 2-diphenyl-l-picrylhydrazyl. The evaluation of the homogeneity distribution of the quercetin inside the polymeric network was made by near-infrared chemical imaging and correspondingly statistical analysis. For in vivo biocompatibility investigation, granuloma test in rats was performed correlated with the activity of enzymes involved in oxidative stress as well as immunologic effects of tested supramolecular complexes that include quercetin as therapeutic agent.

Evaluation of the controlled release ability from the poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane) polymer network synthesized in the presence of β-cyclodextrin

The study presents the possibility to use the 2-hydroxyethyl methacrylate—HEMA copolymer with a comonomer with spiroacetal moiety, 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane)-U, as polymer network for loading the indomethacin—INN as drug model, and also, the controlled release evaluation of the prepared bioactive system. The macromolecular compounds were prepared by radical dispersion polymerization in the presence of a pair of surfactants. The use of cyclodextrin as surfactant allowed the building of the host–guest complexes by inclusion of hydrophobic molecules. Also, the cyclodextrin supplemented the hydrogen bonds and the hydrophobic interactions responsible for the stability of the achieved complexes. The copolymers composition and the INN inclusion onto the polymeric matrix were confirmed by FTIR analysis. The porous structure of the lyophilized P(HEMA-U) samples was illustrated by SEM images. The swelling studies evidenced the interdependence between P(HEMA-U) network properties and the spiroacetal moiety amount. Thus, the copolymers presented the increase of the equilibrium swelling degree with pH and temperature. Also, the polymeric matrices manifested dual sensitivity with pH and temperature. The in vitro release of the INN drug from the polymeric network as well as the in vivo experimental studies evidenced the benefit consequence of the spiroacetal compound presence. The clinical observation of the experimental groups does not show any behavioral modifications to suggest a possible toxic effect of these polymeric formulations with and without INN.

Self-linked polymer gels [based on hyaluronic acid and poly (itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro [5.5] undecane)] as potential drug delivery networks

The study is devoted to the development of a new gel system, based on a copolymer between itaconic anhydride and 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane (PITAU) and hyaluronic acid, used as a potential platform for drug delivery. PITAU is characterized by good capacity of gel network formation, and good biocompatibility, while hyaluronic acid, a polysaccharide present in the human body, plays an important role in a variety of biological processes and has been exploited in preclinical and clinical use for over thirty years. The formation of gels from these two interpenetrated polymeric systems was evidenced by SEM microscopy, rheological and swelling measurements. The use of the new polymeric suprastructure as a drug carrier system was tested through in vivo and in vitro investigations by using indomethacin as a model active substance. The samples showed good biocompatibility and an antinociceptive effect in tail flick test. The controlled drug release was also evaluated by in vitro dissolution studies.

Synergic Effects of Pregabalin-Acetaminophen Combination in Somatic and Visceral Nociceptive Reactivity

Background/Aims: The present study investigates the effects of pregabalin (PGB), acetaminophen (ACET) and tenoxicam (TNX) administration in somatic and visceral nociception, using the tail flick test and the writhing test in mice. Methods: In the tail flick test, the substances were administered orally and the latency time response was recorded 15, 30, 60, 90 and 120 min after administration. In the writhing test, pain responses were scored every 5 min during a 30-min period after intraperitoneal injection of diluted acetic acid. Results: Our study demonstrated that oral administration of the combination PGB-ACET resulted in a stronger increase of latency reaction - statistically significant after 15 min compared to TNX and after 30 min compared to PGB in tail flick test. In the writhing test, the combination PGB-ACET, but also PGB-TNX, resulted in a stronger decrease of writhe numbers - statistically significant compared to the effects of the separate administration of each substance. This decrease was more intense in animals treated with the combination PGB-ACET than with PGB-TNX. Conclusion: These results suggest an antinociceptive activity which may be a consequence of the synergic action of the substances.

Nitrosalicyl-imine-chitosan hydrogels based drug delivery systems for long term sustained release in local therapy

The paper focuses on the synthesis and characterization of new drug delivery systems for local therapy. They were prepared by in situ hydrogelation of chitosan biopolymer with nitrosalicylaldehyde in the presence of a model drug, varying the crosslinking density. The structural, supramolecular and morphological characteristics of the systems were studied by FTIR spectroscopy, X-ray diffraction and, POM and SEM microscopy. In vitro release of the drug has been explored in simulated physiological conditions and in vivo release was investigated by the somatic pain model on rats. Information on the biodegradation of the systems was gain by simulating experiments of enzymatic degradation. The systems were biodegradable and showed a prolonged drug release, assuring an in vivo efficient therapeutic effect over 5 days, with no systemic toxicity. All these findings demonstrated that the new hydrogels based on nitrosalicyl-imine-chitosan provides a practical approach for sustained drug delivery for local chemotherapy.