Simulated Physiological Media Research Articles

Effect of nitrogen ion implantation dose on torsional fretting wear behavior of titanium and its alloy

Various doses of nitrogen ions were implanted into the surface of pure titanium, Ti6Al7Nb and Ti6Al4V, by plasma immersion ion implantation. Torsional fretting wear tests involving flat specimens of no-treated and treated titanium, as well as its alloys, against a ZrO2 ball contact were performed on a torsional fretting wear test rig using a simulated physiological medium of serum solution. The treated surfaces were characterized, and the effect of implantation dose on torsional fretting behavior was discussed in detail. The results showed that the torsional fretting running and damage behavior of titanium and its alloys were strongly dependent on the dose of the implanted nitrogen ions and the angular displacement amplitude. The torsional fretting running boundary moved to smaller angular displacement amplitude, and the central light damage zone decreased, as the ion dose increased. The wear mechanisms of titanium and its alloys were oxidative wear, abrasive wear and delamination, with abrasive wear as the most common mechanism of the ion implantation layers.

Effect of oxygen content on deformation mode and corrosion behavior in β-type Ti-Mo alloy

This study examined microstructural characteristics and mechanical properties in a β-type Ti-15Mo alloy (mass%) with different oxygen contents, and their corrosion behavior in simulated physiological media. With increasing oxygen content from 0.1–0.5%, lattice parameter of parent β-phase increased from X-ray diffraction profiles, and spots of athermal ω-phase became weak and diffuse through transmission electron microscopy observations. {332}<113> twin density decreased with an increase in oxygen content from 0.1–0.3% based on electron backscattered diffraction analyses, and it became almost zero when further increased oxygen content up to 0.5%. The solute oxygen atoms led to both a transition of {332}<113> twinning to dislocation slip and a suppression of β-phase to ω-phase transformation. Room-temperature tensile testing of this alloy with oxygen content ranging from 0.1–0.5%, revealed that yield strength ranged from 420MPa to 1180MPa and that uniform elongation ranged from 47–0.2%. The oxygen-added alloys kept a low elastic modulus obtained from stress-strain curves, and exhibited good corrosion resistance in Ringer's solution from open-circuit potential and potentiodynamic polarization measurements. A desirable balance between mechanical properties and corrosion resistance is obtainable in this alloy as biomaterials through utilizing oxygen to control the deformation mode.

Synthesis of Photo- and pH Dual-Sensitive Amphiphilic Copolymer PEG43-b-P(AA76-co-NBA35-co-tBA9) and Its Micellization as Leakage-Free Drug Delivery System for UV-Triggered Intracellular Delivery of Doxorubicin.

Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation, and simple esterification reaction and self-assembled into stimuli-regulated amphiphilic micelles in aqueous solution. On the basis of the optimization of the morphology and particle size of the micelles via modulating the number of the photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from PEG43-b-P(AA76-co-NBA35-co-tBA9) with an average hydrodynamic diameter (Dh) of 163 nm was selected as a potential drug delivery system (DDS) for UV-triggered delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX-loading. Most importantly, the DOX-loaded PEG43-b-P(AA76-co-NBA35-co-tBA9) micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated physiological medium within 6 days without UV-irradiation, indicating their potential as leakage-free DDS. As in the acidic media mimicking the tumor microenvironment, a high cumulative DOX release ratio of 74.70% was achieved within 6 days after UV-irradiation for 20 min, showing a sustained release behavior. Under UV-irradiation, the photolabile o-nitrobenzyl moieties were cleaved off, the amphiphilic copolymer transformed into a water-soluble polymer, favoring the metabolism of drug carriers, and the micelles were demicellized to accelerate the drug release in a triggered or on-demand manner.

PEGylated Oxidized Alginate-DOX Prodrug Conjugate Nanoparticles Cross-Linked with Fluorescent Carbon Dots for Tumor Theranostics.

Theranostic nanomedicine has recently emerged as an appealing approach for tumor chemotherapy. Here, for the first time, fluorescent carbon dots (Cdots) were used as cross-linker for tumor theranostic nanoparticles. Novel theranostic nanoparticles of approximately 27 nm with a doxorubicin (DOX) content of 0.2532 mg/mg (mPEG-OAL-DOX/Cdots) were designed by conjugating DOX onto mPEG-OAL/Cdots nanoparticles that were prepared by cross-linking the PEGylated oxidized alginate (mPEG-OAL) with Cdots. Due to the acid-labile Schiff base conjugating linkage, the theranostic prodrug nanoparticles showed low levels of DOX release in the simulated physiological media, which indicated premature drug leakage could be reduced during body circulation. Interestingly, the in vitro DOX release was triggered in the simulated tumor microenvironment without burst release. MTT assay and CLSM analysis showed that the mPEG-OAL/Cdots nanoparticles were noncytotoxic, but that the mPEG-OAL-DOX/Cdots theranostic nanoparticles exhibited high degrees of inhibition of cancer cells due to their nucleus-targeting DOX delivery. In addition, their cellular fluorescence characteristic demonstrated a potential application for imaging-guided drug delivery in tumor treatment.

Tribological behavior of a Ni-free Zr-based bulk metallic glass with potential for biomedical applications

In this study, the tribological behavior of a Ni-free Zr53Al16Co23·25Ag7.75 bulk metallic glass (BMG) was investigated in dry-sliding and simulated physiological media using ball-on-disk reciprocating friction. The effects of sliding load, speed, media and counterpart materials on the wear resistance of the Zr–Al–Co–Ag BMG were illustrated. Under dry-sliding in air, wear resistance of the Zr-based BMG decreases with increasing sliding load, and wear deterioration is controlled by oxidation and abrasive wear. With increasing sliding velocity, larger plastic deformation occurs on the surface of BMG due to the frictional heat. The BMG exhibits decreased wear resistance in 0.9% NaCl and phosphate buffer saline (PBS) solutions in comparison with that in air and deionized water, which is probably associated with tribocorrosion controlled by synergistic effects of abrasive and corrosive wear. The wear resistance of the Zr-based BMG against Si3N4 counterpart material is inferior to that against ZrO2, whereas the case is contrary to that against Al2O3. The effect of ceramic counterpart materials on the wear resistance of BMG is discussed based on their Young's modulus and fracture toughness.

Electrochemical behavior of titanium modified with TiO2 nanotubes

Event Abstract Back to Event Electrochemical behavior of titanium modified with TiO2 nanotubes Nilson Oliveira1 and Claudemiro Bolfarini1 1 Federal University of São Carlos – UFSCar, Department of Materials Engineering – DEMa, Brazil Introduction: It is know that the physicochemical properties of the biomaterial surface influence the biological response of an implant, and as Ti is considered a bioinert metal, it is necessary to use surface modification methods in order to improve its osseointegration [1]-[3]. It is important to develop materials and surfaces with adequate corrosion resistance, which is a necessary condition for the biocompatibility [4],[5]. Considering that nanotubes layers on the Ti surface can enhance the osseointegration [6],[7], the aim of the present work was to obtain nanotubes on the Ti surface and to study its electrochemical behavior in a simulated physiological media. Materials and Methods: Nanotubes were obtained on Ti (grade II) surface by anodic oxidation, using a two electrode system [8],[9]. The electrochemical anodization was performed applying 10V/1h, 20V/1h or 20V/2h, using as working electrolyte Glycerol / H2O / NaF [8]. The electrochemical analyses were carried out using a standard three-electrode cell, a saturated Ag/AgCl electrode as reference, and Ringer Physiological solution [8]-[10]. The open circuit potential values, Eoc, were monitored until 144h of immersion, and the polarization measurements were performed from -0.100 mV up to 1.5V (vs Eoc) at 1mV/s. Results and Discussion: After anodization, it was obtained well-defined nanotubes on the entire surface of all samples, with average diameter of 45nm for 10V and 90nm for 20V, and length of 1µm for 1h and 2 µm for 2h, consistent with previous work[8]. Exemplifing, in the Fig.1 are presented SEM micrographs for 10V and 20V for 1 h. Figure 1 - SEM micrographs of nanotubes layer formed at (a) 10V / 1h and (b) 20V / 1h. The Eoc profiles were similar (Fig.2a), indicating that the nanotubes films formed are not suffering spontaneous dissolution and also that the different diameters and lengths are not influencing their electrochemical properties. These values are higher than the values found by Oliveira & Guastaldi[5] for cp Ti polished after 360h immersion in Ringer's solution: -200mV (vs SCE). The voltammetric profiles are similar for all surfaces (Fig. 2b), with low current values​​, on the order of µA, without the occurrence of transpassivation in the potential range studied, indicating the presence of a barrier-type oxide film[5], that is probably related to the oxide layer at the bottom of the nanotubes. The shift of the corrosion potential from -600 mV (as polished surface) to -300mV (nanotubes surfaces) indicates that the presence of the nanotubes is improving the Ti corrosion resistance. The variation in diameter and length of the nanotubes did not influence their electrochemical behavior, confirming the results obtained in the Eoc measurements. Figure 2 – (a) Open-circuit potential measurements and (b) potentiodynamic polarization for Ti with nanotubes layer formed at 10V / 1h, 20V / 1h, and 20V / 2h. Conclusion: The nanostructured layers formed on pure Ti with different diameters and length of the nanotubes improved the electrochemical stability and corrosion resistance of the Ti. The authors are grateful to FAPESP for scholarships (proc. 2012/11350-0) and grants (2012/01652-9).

A Robust Infinite Zirconium Phenolate Building Unit to Enhance the Chemical Stability of Zr MOFs

AbstractA novel Zr‐chain based MOF, namely MIL‐163, was designed and successfully synthesized using a bis‐1,2,3‐trioxobenzene ligand. Endowed with large square‐shaped channels of 12 Å width, it shows remarkable water uptake (ca. 0.6 cm3 g−1 at saturating vapor pressure) and a remarkable stability in simulated physiological media, where archetypical Zr carboxylate MOFs readily degrade.

A Robust Infinite Zirconium Phenolate Building Unit to Enhance the Chemical Stability of Zr MOFs.

A novel Zr-chain based MOF, namely MIL-163, was designed and successfully synthesized using a bis-1,2,3-trioxobenzene ligand. Endowed with large square-shaped channels of 12 Å width, it shows remarkable water uptake (ca. 0.6 cm(3) g(-1) at saturating vapor pressure) and a remarkable stability in simulated physiological media, where archetypical Zr carboxylate MOFs readily degrade.

Cabozantinib Loaded DSPE-PEG2000 Micelles as Delivery System: Formulation, Characterization and Cytotoxicity Evaluation

Cabozantinib, a potent pan-tyrosine kinase inhibitor, has been reported to provide enhanced antitumor efficacy by simultaneously inhibiting both MET and VEGF pathways, which are critical to tumor angiogenesis, survival and migration. It's very poor water solubility prevents its administration by the intravenous route, which may be important in patients unable to take the drug orally. In this study, we developed an efficient PEG-lipid-based polymeric micelle formulation with enhanced drug solubility and stability for cabozantinib delivery. DSPE-PEG2000 micelles encapsulating cabozantinib were prepared by a thin-film rehydration method followed by a lyophilization process to generate the dry dosage form. The average hydrodynamic diameter of freshly prepared micelles was 11 nm with a narrow size distribution, and the dry micelle cake could be fully reconstituted by rehydration. Approximately 75% of the drug was encapsulated into the lyophilized cake, and a sustained drug release profile was observed in simulated normal physiological release medium. Compared with the free cabozantinib solution, the drug-loaded micelles displayed significantly enhanced intracellular accumulation and cytotoxicity in human glioblastoma cancer cells and non-small lung cancer cells. These results suggest that the micellar formulation of cabozantinib may serve as a promising nanocarrier in anticancer treatments.

Corrosion behavior of as-cast and hot rolled pure magnesium in simulated physiological media

Magnesium is a biodegradable metal that has significant potential advantages as an implant material. However, the fast degradation rate in the biological environment has limits the application. In this article, corrosion behaviors of as-cast and hot rolled pure magnesium in 0.9% NaCl, Ringer’s, and Tas-SBF solutions were studied. Potentiodynamic polarization and hydrogen evolution test were employed to assess the corrosion behaviors. The magnesium specimens were characterized using field emission scanning electron microscopy equipped with energy-dispersive X-ray analysis and X-ray diffraction. The as-cast specimens in 0.9% NaCl and Ringer’s solutions had lower corrosion potentials and corrosion rates than the hot rolled specimens. However, the as-cast specimen in the Tas-SBF solution had a higher corrosion potential and a lower corrosion rate than the hot rolled specimen. Only the specimens in the Tas-SBF solution showed passivation behavior due to the presence of HCO3 − ions. The hot rolled specimen could form apatite more easily on its surface than the as-cast specimen in Tas-SBF.

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.

Electrochemical Behavior of Novel Superelastic Biomedical Alloys in Simulated Physiological Media Under Cyclic Load

The aim of the present work was to study corrosion and electrochemical behavior of Ti-22Nb-6Ta and Ti-22Nb-6Zr (at.%) superelastic alloys under conditions which imitate the performance mode of target devices (bone implants), i.e., under cyclic load in simulated physiological solutions. Open circuit potential (OCP) measurements were carried out on wire specimens in Hank’s solution and artificial saliva at 37 °C with various strain values up to 1.5%. It is shown that at clinically relevant strain values (about 0.2%) the alloys exhibit OCP growth indicating their high stability and resistance to corrosion fatigue under these cycling conditions. At much higher strains (about 1%), fatigue crack initiation and propagation take place, however, the corresponding OCP variation indicates that the fracture process is significantly restrained by reversible martensitic transformation during cycling.

Electrochemical noise measurements of AISI 316L during wear in simulated physiological media

Electrochemical noise has been used to study the tribocorrosion behaviour of austenitic stainless steel AISI 316 in two different simulated body fluid solutions [phosphate buffer solution (PBS) and PBS plus bovine serum albumin). The analysis of potential and current transients permits not only the determination of the contribution of the aggressive medium to the total volume loss due to synergism between wear and corrosion but also the detection of changes in the mechanism produced by the mechanical/electrochemical attack.

Tribological properties of Zr61Ti2Cu25Al12 bulk metallic glass under simulated physiological conditions

In this work, wear resistance of a Zr61Ti2Cu25Al12 (ZT1) bulk metallic glass (BMG) in dry-sliding and simulated physiological media was investigated using ball-on-flat tribological approach and Si3N4 ball as counterpart. It was indicated that wear resistance of the BMG in air and deionized water is superior to Ti6Al4V alloy but inferior to 316L stainless steel (316L SS) and Co28Cr6Mo (CoCrMo) alloy. However, under simulated physiological media such as phosphate buffered solution (PBS) and Dulbecco's modified Eagle medium with 10vol.% fetal bovine serum (DMEM+FBS), the ZT1 BMG exhibits decreased wear resistance in comparison with the Ti6Al4V, 316L SS and CoCrMo. This is probably associated with its moderate pitting corrosion resistance in the medium containing chloride ions. The presence of protein in the solution has a significant effect to ruin pitting resistance of the BMG, then causing more severe wear damage. Under the dry-wear condition, abrasive wear is a predominant wear mechanism for the ZT1, whereas under deionized water, deterioration induced by abrasive wear can be mitigated. In simulated physiological media, wear deterioration is a typical tribocorrosion controlled by synergistic effects of the abrasive and corrosive wear. For the four investigated metals, wear resistance does not exhibit distinct correlation with hardness, whereas the material with high Young's modulus possesses better wear resistance.

Electrochemical behavior of (Ti1−xNbx)5Si3 nanocrystalline films in simulated physiological media

In this paper, (Ti1−xNbx)5Si3 nanocrystalline films were synthesized and their potential as highly corrosion-resistant coatings for the biomedical alloy Ti–6Al–4V was explored. To assess the electrochemical behavior of the as-deposited films, the samples were immersed in Ringer’s solution open to air at 37°C. The processes that govern the electrochemical reactions at the film surface were analyzed using a combination of complementary electrochemical measurement techniques such as potentiodynamic polarization, electrochemical impedance spectroscopy and Mott–Schottky analysis. The results show that the (Ti1−xNbx)5Si3 nanocrystalline films offer Ti–6Al–4V a strong shield from corrosive attack and the addition of Nb in the films greatly enhances their resistance to corrosion, and in so doing, minimizes metal ion release. Collectively, our data suggest that (Ti1−xNbx)5Si3 nanocrystalline films as supreme coatings with anti-corrosive properties have potential to improve the performance and extend the service life of orthopedic and cochlear implants.

Poly-l-asparagine nanocapsules as anticancer drug delivery vehicles

This work presents for the first time the development of novel poly-l-asparagine (PASN) nanocapsules and the in vitro evaluation of their potential as anticancer drug delivery systems. The design of PASN nanocapsules was inspired by the well-known avidity of cancer cells for the amino acid l-asparagine together with the expected ability of this hydrophilic polymer to escape to the mononuclear phagocytic system. Besides, these nanocapsules have an oily reservoir, which enables the efficient encapsulation of lipophilic drugs. PASN nanocapsules were obtained by an emulsification-polymer layer deposition process, which involves using a cationic surfactant as a bridge for the interaction of PASN with the lipid core. PASN nanocapsules showed sizes of around 170–200nm and negative zeta potential values (around −20mV to −40mV). The model anticancer drug docetaxel was efficiently encapsulated (around 75%) and retained within the nanocapsule’s structure upon dilution in a simulated physiological medium. Moreover, these nanocapsules exhibited the ability to interact with the NCI-H460 human cancer cells and to enhance the cellular toxicity of the anticancer drug. All these features together with their adequate stability profile render these nanocapsules a new attractive platform for anticancer intracellular drug delivery.

Surface Charge-Switchable Polymeric Magnetic Nanoparticles for the Controlled Release of Anticancer Drug

We develop paclitaxel (PTX) and magnetic nanoparticles (MNPs) coencapsulated, surface charge-switchable, thermosensitive poly(d,l-lactic-co-glycolic acid)-l-lysine-d-galactose (PTX-MNP-PLGA-Lys-Gal) NPs for the controlled release of the anticancer drug. The novel dual signal-responsive nanovehicle is formulated to shield off target at pH 7.4 but bind avidly to tumor cells in acidity, alleviating toxicity and side effects of the drug to normal tissues. The mechanism involves pH-sensitive NPs surface charge switching by the deblocking process of galactose molecules followed by protonation of ε-NH2 in lysine residue at acidic pH. Magnetic hyperthermia under near infrared (NIR) irradiation induced the contraction of PTX-MNP-PLGA-Lys-Gal NPs and, in turn, triggered burst release of PTX. Transmission electron microscopy (TEM), fluorescence microscope analyses, Fourier transform infrared (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), dynamic light scattering (DLS), and ξ-potential analyses were performed to characterize physicochemical properties of the as-prepared NPs. The size range of the globule PTX-MNP-PLGA-Lys-Gal NPs after being prescreened was from 130 to 150 nm under simulated physiological medium. The high encapsulation efficiencies of MNPs and PTX were obtained, reaching 85 and 78 wt % for PTX-MNP-PLGA-Lys-Gal NPs, respectively. The tumor inhibitory rate of 78.8% reflected that the resulting NPs could be promising to treat cancer by specific binding and targeting release drug to tumor.

Thermosensitive self‐assembly micelles from A2BA2‐type poly(N‐isopropyl acrylamide)2‐b‐Poly(lactic acid)‐b‐Poly(N‐isopropyl acrylamide)2 four‐armed star block copolymers and their applications as drug carriers

ABSTRACTA novel A2BA2‐type thermosensitive four‐armed star block copolymer, poly(N‐isopropyl acrylamide)2‐b‐poly(lactic acid)‐b‐poly(N‐isopropyl acrylamide)2, was synthesized by atom transfer radical polymerization and characterized by 1H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography. The copolymers can self‐assemble into nanoscale spherical core–shell micelles. Dynamic light scattering, surface tension, and ultraviolet–visible determination revealed that the micelles had hydrodynamic diameters (Dh) below 200 nm, critical micelle concentrations from 50 to 55 mg/L, ζ potentials from −7 to −19 mV, and cloud points (CPs) of 34–36°C, depending on the [Monomer]/[Macroinitiator] ratios. The CPs and ζ potential absolute values were slightly decreased in simulated physiological media, whereas Dh increased somewhat. The hydrophobic camptothecin (CPT) was entrapped in polymer micelles to investigate the thermo‐induced drug release. The stability of the CPT‐loaded micelles was evaluated by changes in the CPT contents loaded in the micelles and micellar sizes. The MTT cell viability was used to validate the biocompatibility of the developed copolymer micelle aggregates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4137–4146, 2013

Rationale of Drug Encapsulation and Release from Biocompatible Porous Metal–Organic Frameworks

A joint experimental and computational systematic exploration of the driving forces that govern (i) encapsulation of active ingredients (solvent, starting material dehydration, drug/material ratio, immersion time, and several consecutive impregnations) and (i) its kinetics of delivery (structure, polarity, ...) was performed using a series of porous biocompatible metal–organic frameworks (MOFs) that bear different topologies, connectivities, and chemical compositions. The liporeductor cosmetic caffeine was selected as the active molecule. Its encapsulation is a challenge for the cosmetic industry due to its high tendency to crystallize leading to poor loadings (<5 wt %) and uncontrolled releases with a subsequent low efficiency. It was evidenced that caffeine entrapping reaches exceptional payloads up to 50 wt %, while progressive release of this cosmetic agent upon immersion in the simulated physiological media (phosphate buffer solution pH = 7.4 or distilled water pH = 6.3, 37 °C) occurred mainly depend...

Investigation of Electrochemical Behavior of Novel Superelastic Biomedical Alloys in Simulated Physiological Media

This paper focuses on study of the kinetics and the mechanism of passive film formation on novel superelastic biomedical Ti-22Nb-6Ta and Ti-21.8Nb-6Zr (at.%) alloys in simulated physiological solutions using XPS and electrochemical techniques in comparison with commercially pure titanium and Nitinol. In vitro biocompatibility study of Ti-22Nb-6Ta alloy was carried out as well. Ti-22Nb-6Ta alloy manifests a strong trend to protective passive film formation during the first stage of oxidation in simulated physiological solutions. It is shown that Ti-22Nb-6Ta and Ti-21.8Nb-6Zr electrochemical characteristics are comparable to those of titanium and Nitinol, and the alloy can be recommended for use in implantology.