Spectroscopic investigation on the sonodynamic activity of amsacrine (AMSA) to bovine serum albumin (BSA) damage

The sonodynamic damage of bovine serum albumin (BSA) under ultrasonic irradiation in the presence of amsacrine (AMSA) was studied by hyperchromic effect of UV-vis spectra and quenching effect of intrinsic fluorescence. In addition, several influencing factors such as ultrasonic irradiation time, AMSA concentration, system acidity and ionic strength about the damage of BSA molecules were reviewed. The results showed that the damage degree was obviously enhanced with the increase of ultrasonic irradiation time and AMSA concentration, but it was only slightly increased with the increase of solution pH value and ionic strength. Furthermore, the binding and damaging sites to BSA molecules were estimated by synchronous fluorescence spectra. The different chances to damage tryptophan (Trp) and tyrosine (Tyr) residues were found through the ratios of synchronous fluorescence quenching (R_SFQ). At last, the generation of reactive oxygen species (ROS) in sonodynamic process was estimated by the method of oxidation-extraction Spectrometry (OES). And then, several radical scavengers were used to determine the kind of ROS, which includes singlet oxygen (¹O₂) and hydroxyl radicals (·OH). Perhaps, the result would bring a certain guiding significance to use sonosensitive drugs in the fields of tumor treatment.     

Spectroscopic studies on the interaction and sonodynamic damage of neutral red (NR) to bovine serum albumin (BSA)

In this paper, the interaction of neutral red (NR) with bovine serum albumin (BSA) and the sonodynamic damage to BSA under ultrasonic irradiation was studied by means of ultraviolet-visible (UV-vis) and fluorescence spectra. The quenching constant (K_SV=5.749×10⁴ L/mol), binding constant (K_A=3.19×10⁴ L/mol) and binding site number (n=0.9462) were measured. The binding distance (r=2.47 nm) between NR and BSA was obtained according to Föster’s non-radiative energy transfer theory. The damage process of BSA molecules was detected by the hyperchromic effect of UV-vis spectra and quenching of intrinsic fluorescence spectra. In addition, the influencing factors such as ultrasonic irradiation time and NR concentration on the damage to BSA molecules were also considered. The results showed that the damage degree is enhanced with the increase of ultrasonic irradiation time and NR concentration. The possible mechanism of sonodynamic damage to BSA molecules was mainly mediated by singlet oxygen (¹O₂). Otherwise, the binding and damaging sites to BSA molecules were also estimated by synchronous fluorescence. The results indicated that the NR is more vicinal to tryptophan (Trp) residue than to tyrosine (Tyr) residue and the damage site is also mainly at Trp residues. The research result will bring a certain significance to use sonosensitive drugs in the fields of tumor treatment.     

Spectroscopic investigation on the sonodynamic activity of Safranine T to bovine serum albumin damage

In this paper, the Safranine T (ST) was used as sonosensitive compound to study the sonodynamic damage to bovine serum albumin (BSA) under ultrasonic irradiation using fluorescence and UV–vis spectroscopy. The experimental results revealed the obvious synergetic effect of Safranine T (ST) and ultrasonic irradiation during the damage of BSA molecules. In addition, some influencing factors such as ultrasonic irradiation time, Safranine T (ST) concentration, pH value and ionic strength on the sonodynamic damage of BSA molecules were also considered. Finally, the generation of reactive oxygen species (ROS) in sonodynamic process was estimated by the method of Oxidation-Extraction Photometry (OEP). Meanwhile, several radical scavengers were used to determine the kind of generated ROS. Experiments showed that under ultrasonic irradiation the Safranine T (ST) can generate several kinds of ROS at the same time, at least including singlet oxygen (¹O₂) and hydroxyl radicals (OH).     

Characterization of ultrasound-mediated destruction of drug-loaded microbubbles using an improved in vitro model

Introduction

Ultrasound mediated destruction of microbubbles (MBs) has become a promising tool for site specific drug and gene delivery. One of the most important properties of drug-loaded MBs is their destructibility by ultrasound. Therefore, the aim of this study was to establish a new in vitro model that allows evaluation of the kinetics of ultrasound-mediated MB destruction at near physiological conditions.In this work, a newly developed drug-loaded MB formulation was compared with unloaded MBs in order to assess the influence of drug-loading on their acoustic destructibility. Furthermore, drug-loaded MBs were compared to acoustically active lipospheres (AALs), comprising an additional layer of triacetin, as well as to a marketed MB contrast agent (SonoVue^®, Bracco Diagnostics, USA), used as standard.

Methods

MBs with phospholipid monolayer shells were produced by mechanical agitation of liposomal dispersions and octafluoropropane gas. AALs were accordingly produced by agitation of phospholipid-stabilized aqueous triacetin microemulsions with gas.The in vitro experimental setup for acoustic destructibility testing comprised a membrane cell, pressurized and brought to 37 °C in order to imitate human blood pressure and body temperature. The optimized egg-like cell shape provided optimal flow conditions and a minimized dead volume.Ultrasound with frequencies of 1 and 3 MHz and intensities, varying from 1 to 4 W/cm², was applied through a silicone membrane window to the cell. MB size distribution and concentration were measured by light blockage in equal time intervals during the sonication.

Results

The optimized in vitro setup demonstrated differences in the ultrasound destructibility of the MB formulations used. The fastest decay upon ultrasound exposure was found for SonoVue^®. Unloaded and drug-loaded MBs appeared to be comparably destructible to SonoVue^®. AALs were about 4.5-fold more stable than SonoVue^®. MB destructibility was also found to depend on particle diameter, corresponding to theoretical models described in the literature.

Conclusion

The optimized in vitro setup has rendered a fast and reliable laboratory tool for characterization of MB formulations.     

Quantitative analysis of oxidative DNA damage induced by high-voltage pulsed discharge with cavitation

Pulsed discharge is used for sterilization and disinfection, but the details of the molecular mechanisms remain largely unknown. Since pulsed discharge generates reactive oxygen species (ROS), we analyzed the oxidative DNA damages after pulsed discharge treatment to consider the involvement of ROS in the damaging process. We applied pulsed discharge with cavitation to plasmid DNA molecules and estimated the yields of the damages by agarose gel electrophoresis. The treated DNA contained various oxidative DNA damages, including single and double strand breaks and base lesions. The yields of the damages increased in response to the energy used for pulsed discharge. We also measured the yield of 8-hydroxyguanine (8-OH-G), one of the major oxidative base lesions, in the treated plasmid DNA by mass spectrometry quantitatively and found that the yield of the oxidative base lesion corresponded to the increment of the applied energy. In addition, we observed the involvement of mutM gene, which is responsible for repair of 8-OH-G, in the increased sensitivity of Escherichia coli to pulsed discharge. Therefore, ROS seem to mediate the sterilization ability of pulsed discharge.     

New insights on the role of ROS in the mechanisms of sonoporation-mediated gene delivery

Reactive oxygen species (ROS) are hypothesized to play a role in the sonoporation mechanisms. Nevertheless, the acoustical phenomenon behind the ROS production as well as the exact mechanisms of ROS action involved in the increased cell membrane permeability are still not fully understood. Therefore, we investigated the key processes occurring at the molecular level in and around microbubbles subjected to ultrasound using computational chemistry methods. To confirm the molecular simulation predictions, we measured the ROS production by exposing SonoVue® microbubbles (MBs) to ultrasound using biological assays. To investigate the role of ROS in cell membrane permeabilization, cells were subjected to ultrasound in presence of MBs and plasmid encoding reporter gene, and the transfection level was assessed using flow cytometry. The molecular simulations showed that under sonoporation conditions, ROS can form inside the MBs. These radicals could easily diffuse through the MB shell toward the surrounding aqueous phase and participate in the permeabilization of nearby cell membranes. Experimental data confirmed that MBs favor spontaneous formation of a host of free radicals where HO was the main ROS species after US exposure. The presence of ROS scavengers/inhibitors during the sonoporation process decreased both the production of ROS and the subsequent transfection level without significant loss of cell viability. In conclusion, the exposure of MBs to ultrasound might be the origin of chemical effects, which play a role in the cell membrane permeabilization and in the in vitro gene delivery when generated in its proximity.     

Enhanced production of hypocrellin A by ultrasound stimulation in submerged cultures of Shiraia bambusicola

Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28 W/cm² at 40 kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12 h to stimulate HA production of Shiraia bambusicola after 72 h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247.67 mg/L) on day 8. US could result in the decreased pellet diameter, the enhanced membrane permeability, the alternation of membrane compounds and reactive oxygen species (ROS) generation. Furthermore, the ultrasonic treatment up-regulated the expression of some HA biosynthetic genes including polyketide synthase gene (PKS), O-methyltransferase gene (Omef), O-methyltransferase/FAD-dependent monooxygenase (Mono) and FAD/FMN-dependent oxidoreductase gene (FAD), and activated major facilitator superfamily transporter gene (MFS) for HA exudation. The enhancement of HA production was mainly due to both the stimulated cellular biosynthesis and the enhanced fungal exudation of HA. These results provide a basis for understanding the US elicitation and a valuable strategy for enhancing HA production in submerged Shiraia cultures.     

Study on the surface bioactivity of novel magnetic A-W glass ceramic in vitro

Novel magnetic A-W glass ceramic (M GC) in the system MgO-CaO-SiO₂-P₂O₅-CaF₂-MnO-ZnO-Fe₂O₃ was synthesized by doping Mn-Zn ferrite to apatite-wollastonite glass ceramic. The phase composition was investigated by XRD. The magnetic property was measured by VSM. The in vitro bioactivity was tested by immersion in simulated body fluid. The result shows apatite, wollastonite, fluorapatite and Zn_0.75Mn_0.75Fe_1.5O₄ are the main phases of M GC. Under a magnetic field of 10,000 Oe, the saturation magnetization and coercive force of the material are 6 emu g⁻ and 180 Oe, respectively. After soaking in SBF for 14 days, the surface of M GC is coated by a hydroxycarbonate apatite layer.     

Carotid atherosclerotic plaque characterisation by measurement of ultrasound sound speed in vitro at high frequency, 20 MHz

This study aimed to utilise a tissue mimicking material (TMM) in order to embed in vitro carotid plaque tissue so that its acoustic properties could be assessed. Here, an International Electrotechnical Commission (IEC) agar-based TMM was adapted to a clear gel by removal of the particulates. This clear TMM was measured with sound speed at 1540 ms⁻¹ and an attenuation coefficient of 0.15 dB cm⁻¹ MHz⁻¹. Composite sound speed was then measured through the embedded material using a scanning acoustic microscope (SAM). Both broadband reflection and transmission techniques were performed on each plaque specimen in order to ensure the consistency of the measurement of sound speed, both at 21 °C and 37 °C. The plaque was measured at two temperatures to investigate any effect on the lipid content of the plaque. The contour maps from its associated attenuation plots were used to match the speed data to the photographic mask of the plaque outline. This physical matching was then used to derive the sound speed from the percentage composition seen in the histological data by solution of simultaneous equations. Individual speed values for five plaque components were derived; TMM, elastin, fibrous/collagen, calcification and lipid. The results for derived sound speed in the TMM were consistently close to the expected value of soft tissue, 1540 ms⁻¹. The fibrous tissue showed a mean value of 1584 ms⁻¹ at 37 °C. The derived sound speeds for elastic and lipid exhibited large inter-quartile ranges. The calcification had higher sound speed than the other plaque components at 1760–2000 ms⁻¹. The limitations here lay in the difficulties in the matching process caused by the inhomogeneity of the plaque material and shrinkage during the histological process. Future work may concentrate on more homogeneous material in order to derive sound speed data for separate components. Nevertheless, this study increases the known data ranges of the individual components within a plaque. This information may be used help to assess the mechanical properties and structural integrity and its associated vulnerability or risk of embolization in future diagnostic ultrasound techniques.     

Excitation of ultrasonic Lamb waves using a phased array system with two array probes: Phantom and in vitro bone studies

Long bones are good waveguides to support the propagation of ultrasonic guided waves. The low-order guided waves have been consistently observed in quantitative ultrasound bone studies. Selective excitation of these low-order guided modes requires oblique incidence of the ultrasound beam using a transducer-wedge system. It is generally assumed that an angle of incidence, θ_i, generates a specific phase velocity of interest, c_o, via Snell’s law, θ_i = sin⁻¹(v_w/c_o) where v_w is the velocity of the coupling medium. In this study, we investigated the excitation of guided waves within a 6.3-mm thick brass plate and a 6.5-mm thick bovine bone plate using an ultrasound phased array system with two 0.75-mm-pitch array probes. Arranging five elements as a group, the first group of a 16-element probe was used as a transmitter and a 64-element probe was a receiver array. The beam was steered for six angles (0°, 20°, 30°, 40°, 50°, and 60°) with a 1.6-MHz source signal. An adjoint Radon transform algorithm mapped the time-offset matrix into the frequency-phase velocity dispersion panels. The imaged Lamb plate modes were identified by the theoretical dispersion curves. The results show that the 0° excitation generated many modes with no modal discrimination and the oblique beam excited a spectrum of phase velocities spread asymmetrically about c_o. The width of the excitation region decreased as the steering angle increased, rendering modal selectivity at large angles. The phenomena were well predicted by the excitation function of the source influence theory. The low-order modes were better imaged at steering angle ?30° for both plates. The study has also demonstrated the feasibility of using the two-probe phased array system for future in vivo study.     

Spectroscopic study on the sonodynamic and sonocatalytic damage of anthraquinone derivants to bovine serum albumin under ultrasonic irradiation

In this work, three anthraquinone derivants (Alizarin: 1,2-dihydroxy-9, 10-anthraquinone, Alizarin–DA: 1,2-dihydroxy-9, 10-anthraquinone-3-aminomethyl-N, N-diacetic acid and Alizarin–DA–Fe: 1,2-dihydroxy-9, 10-anthraquinone-3-aminomethyl-N, N-diacetate-Ferrous(III)) were used to study the sonodynamic and sonocatalytic damage of bovine serum albumin (BSA) molecules according to the hyperchromic effect of UV–vis spectra and quenching effect of intrinsic fluorescence. Meanwhile, some influencing factors such as ultrasonic irradiation time, anthraquinone derivants concentration and ionic strength on the damage of BSA molecules were also considered. The results show that the synergetic effect of anthraquinone derivants and ultrasonic irradiation can efficiently damage the BSA molecules. Finally, some special radical scavengers were used to determine the kind of generated reactive oxygen species (ROS) in the presence of three anthraquinone derivants under ultrasonic irradiation. The results show that the ROS, at least, including singlet oxygen (¹O₂) and hydroxyl radicals (OH) are generated during the sonodynamic and sonocatalytic processes. It is wished that this paper could offer some valuable references for the application of anthraquinone derivants in sonodynamic therapy (SDT) and sonocatalytic therapy (SCT) for tumor treatment.     

Effects of high-energy ultrasound on the functional properties of proteins

In recent years, high-energy ultrasound has been used as an alternative to improve the functional properties of various proteins, such as from milk, eggs, soy and poultry. The benefits of implementing this technology depend on the inherent characteristics of the protein source and the intensity and amplitude of the ultrasound, as well as on the pH, temperature, ionic strength, time, and all of the variables that have an effect on the physicochemical properties of proteins. Therefore, it is necessary to establish the optimal conditions for each type of food. The use of ultrasound is a promising technique in food technology with a low impact on the environment, and it has thus become known as a green technology. Therefore, this review focuses on the application of high-energy ultrasound to food; its effects on the functional properties of proteins; and how different conditions such as the frequency, time, amplitude, temperature, and protein concentration affect the functional properties.     

碱性介质电催化体系活性氧的生成及其光谱学研究

亚熔盐液相氧化技术可在相对低温下实现难分解两性金属矿物的高效转化,基于此进一步提出了碱性介质电化学活性氧协同强化新方法。利用紫外-可见光光谱和电子自旋共振波谱等手段对电催化体系活性氧的生成与转化机理进行了系统解析。通过阴极电催化的作用,在电极表面定向进行两电子氧气还原反应,原位产生大量的活性氧组分。研究发现过渡金属离子与两电子氧气还原产物HO-₂之间的“自诱发”效应,可生成具有更高氧化活性的羟基自由基,大幅促进两性金属转化过程,实现了碱性介质电化学高级氧化过程。利用紫外-可见光光谱检测到电化学体系活性氧催化氧化低价两性金属氧化物(Cr₂O₃和V₂O₃)的转化过程。与此同时,根据标准自由能变化的热力学数据计算可知,V₂O₃比Cr₂O₃更易在活性氧存在的条件下发生溶出反应。采用电子自旋共振波谱(ESR)对电催化体系内的羟基自由基进行检测,结果表明由V₂O₃引发的电化学-类Fenton反应激发产生的羟基自由基ESR信号比Cr₂O₃信号强。利用猝灭剂实验验证了具有高氧化电位的羟基自由基可以对两性金属液相氧化起到促进作用。该研究为碱性介质电化学矿物溶出实际反应提供理论参考。     

光谱法结合分子动力学模拟研究臭氧对肌红蛋白结构的作用机制

臭氧(O₃)是一种具有强氧化性作用的杀菌消毒剂,因其安全无害等特点已被广泛用于肉制品生产加工的减菌处理,但O₃减菌处理对红肉色泽具有较强的负面作用,且其作用机制尚缺乏研究。针对肌红蛋白（Mb）存在状态是决定红色肉色泽关键因素的基础,通过紫外-可见吸收光谱法、荧光光谱法和圆二色光谱法（CD）研究O₃作用下Mb的光谱特性变化,结合蛋白质氧化特征指标分析和分子动力学模拟技术探究O₃对Mb分子的作用效果与机制。光谱研究结果表明,O₃处理可使Mb的紫外-可见光谱图在412 nm左右处的铁卟啉环特征峰及540和580 nm附近的氧合肌红蛋白（OMb）特征峰的强度减弱,其中铁卟啉环特征峰发生蓝移;利用固定激发波长280 nm下测定Mb内源性荧光和同步荧光光谱表明O₃会降低Mb的荧光强度,增大铁卟啉基团贡献的荧光峰强度和造成酪氨酸残基荧光光谱特征峰的蓝移;O₃作用使Mb三维荧光光谱特征峰强度的下降及光散射强度的增加。以上变化推断出O₃会促进Mb的氧化,造成其氨基酸残基疏水基团裸露,使Mb所处微环境及其蛋白构象改变;CD分析表明O₃与肌红蛋白接触时间越久,蛋白质二级结构变化越明显,造成α-螺旋的含量下降,无规则卷曲增加。辅以检测不同强度O₃处理Mb的含量及性质的变化,可知O₃处理使OMb含量下降,高铁肌红蛋白（MMb）含量增加,同时O₃处理Mb的羰基含量增加和巯基含量下降,这也进一步证实O₃作用促进了Mb的氧化,此外,O₃处理Mb表面疏水性的增强,说明O₃造成Mb体系微环境的极性变化。分子动力学模拟结果显示O₃会提高Mb肽链的RMSD值,影响Mb肽链的稳定性,减弱铁卟啉环与Mb肽链的相互作用;RMSF结果表明Mb活性口袋附近氨基酸残基的变化较大;蛋白质二级结构分析与光谱学试验研究结果一致,Mb的α-螺旋的含量下降,无规则卷曲增加。总而言之,O₃可作用于Mb的氨基酸残基,导致蛋白质二级结构和疏水性改变,并发生蛋白氧化及铁卟啉环暴露,进而引起红色肉色泽发生改变。该研究可为生鲜红肉护色技术制定等提供一定理论依据。     

Effect of surface micro-topography of titanium material on the behaviors of rabbit osteoblast in vitro

To study interactions of osteoblast on different topography surfaces of titanium material through in vitro systems, four kinds of micro-topography surfaces on novel titanium material were investigated. They were laser-scanned surface (LS), sandblasted surface (SS), machine-tooled surface (MS) and polished surface (PS). The titanium samples were seeded with osteoblast and maintained for a period of 1-12 days. Adhesion in 24 h, proliferation in 12 days and ALP activity in 11 days were assessed. The cell morphologies were observed by scanning electron microscopy and fluorescence microscopy. The investigation showed better cell proliferation and best cell osteogenic differentiation on the micro-grooved surface (LS) at the cell scale (50 μm). Furthermore, osteoblast on the micro-grooved surfaces also displayed a more similar morphology to osteoblast in vivo. It was shown that surface micro-texture at the cell scale have a better effect on cell responses than rough surface and surface texture above the cell scale (>100 μm). The regular micro-grooved titanium surface at the cell scale can offer a better cell growth environment compared with the other titanium surfaces.     

Investigation on biological properties of tacrolimus-loaded poly(1,3-trimethylene carbonate) in vitro

The drug-eluting stents have been regarded as a milestone in inhibiting the restenosis of coronary arteries. However, adverse reactions caused by bare-metal stents and non-biodegradable polymer coatings may result in some clinical problems. In this study, a new tacrolimus-eluting stent coated with biodegradable poly(1,3-trimethylene carbonate) (PTMC) is developed. The structures are characterized by Fourier transform infrared (FTIR) analysis, and the wettability is measured by contact angle assay. The biological behaviors are evaluated by the in vitro platelets adhesion test, APTT test, the human umbilical cord artery smooth muscle cells (HUCASMCs), 4′,6-diamidine-2-phenylindole (DAPI) and actin immunofluorescence staining, MTT colorimetric assay. These results show that after blending tacrolimus into PTMC, the anticoagulant behavior is improved, and the adhesion and proliferation of HUCASMCs on samples are inhibited. This work aims to find one kind of surface erosion biodegradable polymers that can be applied as drug-eluting stent coatings.     

Spectroscopic analyses on interaction of bovine serum albumin (BSA) with toluidine blue (TB) and its sonodynamic damage under ultrasonic irradiation

In this paper, the toluidine blue (TB) with tricyclic quinone imide plane structure is used as sonosensitizer to study the interaction and sonodynamic damage to bovine serum albumin (BSA) by UV-vis and fluorescence spectroscopy. The results show that the TB can bind to BSA molecules, obviously, and the synergetic effects of TB and ultrasonic irradiation can efficiently damage the BSA molecules. Otherwise, some influencing factors such as ultrasonic irradiation time, TB concentration, pH value and ionic strength on the damage of BSA molecules were also considered by the numbers. Synchronous fluorescence spectroscopy indicates that the tyrosine (Tyr) residues of BSA molecules are damaged more seriously than the tryptophan (Trp) residues under ultrasonic irradiation.     

Influence of surface topography and pore architecture of alkali-treated titanium on in vitro apatite deposition

Alkali-treated titanium surfaces have earlier shown to induce bone-like apatite deposition. In the present study, the effect of surface topography of two-dimensional and pore architecture of three-dimensional alkali-treated titanium substrates on the in vitro bioactivity was investigated. Titanium plates with a surface roughness of R_a = 0.13 μm, 0.56 μm, 0.83 μm, and 3.63 μm were prepared by Al₂O₃ grit-blasting. Simple tetragonal and face-centered Ti6Al4V scaffolds with spatial gaps of 450-1100 μm and 200-700 μm, respectively, were fabricated by a three-dimensional fiber deposition (3DFD) technique. After alkali treatment, the titanium plates with a surface roughness of R_a = 0.56 μm were completely covered with hydroxyapatite globules after 7 days in simulated body fluid (SBF), while the coverage of the samples with other surface roughness values remained incomplete. Similarly, face-centered Ti₆Al₄ scaffolds with spatial gaps of 200-700 μm exhibited a full surface coverage after 21 days in SBF, while simple tetragonal scaffolds with spatial gaps of 450-1100 μm were only covered for 45-65%. This indicates the importance of surface topography and pore architecture for in vitro bioactivity.     

Influence of ultrasound pretreatment on the subsequent glycation of dietary proteins

The influence of ultrasound treatment on the subsequent glycation process of proteins is controversial. Glycation behaviors of bovine serum albumin (BSA), β-lactoglobulin (β-Lg) and β-casein (β-CN) after ultrasound pretreatment (UP) were compared by both evaluating glycation kinetics and analyzing structural changes of proteins. UP resulted in both unfolding and aggregation behavior in protein samples, which altered the accessibility of the Lys and Arg. Five cycles of UP up-regulated the glycation degree of BSA and β-Lg, possibly due to the unfolding behavior induced by UP, which exposed additional glycation sites. In contrast, 30 cycles of UP induced a dramatic increase (by 97.9 nm) in particle size of BSA, thus burying portions of glycation sites and suppressing the glycation process. Notably, UP had minimal influence on glycation kinetics of β-CN, due to its intrinsic disordered structure. Based on proteomics analysis, the preference of Lys and Arg during glycation was found to be changed by UP in BSA and β-Lg. Four, 3 and 3 unique carboxyethylated lysine residues were identified in glycated BSA after 0, 5 and 30 cycles of UP, respectively. This study suggests that the protein glycation can be affected by UP, depending on the ultrasonication duration and native structure of the protein.     

An in vitro controlled release study of valproic acid encapsulated in a titania ceramic matrix

Despite the therapeutic efficacy of valproic acid towards numerous diseases, its poor bioavailability and systemic side effects pose significant barriers to long term treatment. In order to take advantage of controlled release implants of valproic acid, the drug was encapsulated into titania ceramic matrices via a sol-gel process. The integrity and structure of valproic acid-containing matrices were characterized through the use of FESEM, TEM, and BET analyses. In vitro controlled release studies and kinetic analyses were performed under ambient conditions (25 °C, atmospheric pressure) and controlled release behaviors were studied using a GC-MS method. Results showed first order dependence in the rate of valproic acid release as a function of drug concentrations in the titania ceramic device. A marked dependence on the surface area and pore size distribution with drug loading was also observed. This research opens new possibilities for the design of novel time-delayed controlled release systems for valproic acid encapsulates.