Abstract: The toxicity of bare zinc oxide nanoparticles used as drug carriers may be the result of releasing zinc ions. Thus, zinc oxide nanoparticles modified with galactose were obtained. The process of their formation was conducted in the microwave field. The physicochemical properties of the obtained products were studied. The size and electrokinetic potential were defined by using dynamic light scattering technique. The crystalline properties were assessed by X-ray diffractometry. In order to confirm the formation of the desired products, Fourier-transform infrared spectroscopy was used. Releasing of zinc ions from the prepared products when comparing to the bare oxide was analyzed. It was found out that modification of zinc oxide nanoparticles with galactose limits the releasing of zinc ions which are responsible for the toxic effect of the whole carrier-drug conjugate.
Abstract: The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO2 nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO2 nanoparticles was characterized from 30 nm to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.
Abstract: Handling life-critical systems complexity requires to be equipped with appropriate technology and the right human agents’ functions such as knowledge, experience, and competence in problem’s prevention and solving. Human agents are involved in the management and control of human-machine system’s performance. Documenting human agent’s situation awareness is crucial to support human-machine designers’ decision-making. Knowledge about risks, critical parameters and factors that can impact and threaten automation system’s performance should be collected using preventive and retrospective approaches. This paper aims to document operators’ situation awareness through the analysis of automated organizations’ feedback. The analysis of automated hospital pharmacies feedback helps identify and control critical parameters influencing human machine interaction in order to enhance system’s performance and security. Our human machine system evaluation approach has been deployed in Macon hospital center’s pharmacy which is equipped with automated drug dispensing systems since 2015. Automation’s specifications are related to technical aspects, human-machine interaction, and human aspects. The evaluation of drug delivery automation performance in Macon hospital center has shown that the performance of the automated activity depends on the performance of the automated solution chosen, and also on the control of systemic factors. In fact, 80.95% of automation specification related to the chosen Sinteco’s automated solution is met. The performance of the chosen automated solution is involved in 28.38% of automation specifications performance in Macon hospital center. The remaining systemic parameters involved in automation specifications performance need to be controlled.
Abstract: Ultrasound (US) is widely used in medical field for
a variety diagnostic techniques but, in recent years, it has also
been creating great interest for therapeutic aims. Regarding drug
delivery, the use of US as an activation source provides better
spatial delivery confinement and limits the undesired side effects.
However, at present there is no complete characterization
at a fundamental level of the different signals produced by
sono-activated nanocarriers. Therefore, the aim of this study
is to obtain a metrological characterization of the cavitation
phenomena induced by US through three parallel investigation
approaches. US was focused into a channel of a customized
phantom in which a solution with oxygen-loaded nanodroplets
(OLNDs) was led to flow and the cavitation activity was
monitored. Both quantitative and qualitative real-time analysis
were performed giving information about the dynamics of
bubble formation, oscillation and final implosion with respect
to the working acoustic pressure and the type of nanodroplets,
compared with pure water. From this analysis a possible
interpretation of the observed results is proposed.
Abstract: Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.
Abstract: Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.
Abstract: Nanotherapy is an actual newest mode of treatment numerous diseases using nanoparticles (NPs) loading with different pharmaceuticals. NPs of biodegradable polymeric micelles (PMs) are gaining increased attention for their numerous and attractive abilities to be used in a variety of applications in the various fields of medicine. The present paper deals with the synthesis of a class of biodegradable micelle-forming polymers, namely ABA triblock-copolymer in which A-blocks represent amino-poly(ethylene glycol) (H2N-PEG) and B-block is biodegradable amino acid-based poly(ester amide) constituted of α-amino acid – L-phenylalanine. The obtained copolymer formed micelles of 70±4 nm size at 10 mg/mL concentration.
Abstract: Flow control valves comprise a silicon flexible membrane that deflects against a substrate, usually made of glass, containing pillars, an outlet hole, and anti-stiction features. However, there is a strong interest in using silicon instead of glass as substrate material, as it would simplify the process flow by allowing the use of well controlled anisotropic etching. Moreover, specific devices demanding a bending of the substrate would also benefit from the inherent outstanding mechanical strength of monocrystalline silicon. Unfortunately, direct Si-Si bonding is not easily achieved with highly structured wafers since residual stress may prevent the good adhesion between wafers. Using a thermoplastic polymer, such as parylene, as intermediate layer is not well adapted to this design as the wafer-to-wafer alignment is critical. An alternative anodic bonding method using an intermediate borosilicate layer has been successfully tested. This layer has been deposited onto the silicon substrate. The bonding recipe has been adapted to account for the presence of the SOI buried oxide and intermediate glass layer in order not to exceed the breakdown voltage. Flow control valves dedicated to infusion of viscous fluids at very high pressure have been made and characterized. The results are compared to previous data obtained using the standard anodic bonding method.
Abstract: Recently, graphene has gained much attention because of its unique optical, mechanical, electrical, and thermal properties. Graphene has been used as a key material in the technological applications in various areas such as sensors, drug delivery, super capacitors, transparent conductor, and solar cell. It has a superior quenching efficiency for various fluorophores. Based on these unique properties, the optical sensors with graphene materials as the energy acceptors have demonstrated great success in recent years. During quenching, the emission of a fluorophore is perturbed by a quencher which can be a substrate or biomolecule, and due to this phenomenon, fluorophore-quencher has been used for selective detection of target molecules. Among fluorescence dyes, 1,8-naphthalimide is well known for its typical intramolecular charge transfer (ICT) and photo-induced charge transfer (PET) fluorophore, strong absorption and emission in the visible region, high photo stability, and large Stokes shift. Derivatives of 1,8-naphthalimides have found applications in some areas, especially fluorescence sensors. Herein, the fluorescence quenching of graphene oxide has been carried out on a naphthalimide dye as a fluorescent probe model. The quenching ability of graphene oxide on naphthalimide dye was studied by UV-VIS and fluorescence spectroscopy. This study showed that graphene is an efficient quencher for fluorescent dyes. Therefore, it can be used as a suitable candidate sensing platform. To the best of our knowledge, studies on the quenching and absorption of naphthalimide dyes by graphene oxide are rare.
Abstract: In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.
Abstract: Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.
Abstract: Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe3O4 nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.
Abstract: Liposomes and pegylated liposomes were widely used as drug delivery system in pharmaceutical field since a long time. However, in the former time, polyethylene glycol (PEG) was connected into phospholipid after the liposomes were already prepared. In this paper, we intend to study the possibility of applying phospholipids which already connected with PEG and then they were used to prepare liposomes. The model drug resveratrol was used because it can be applied against different diseases. Cholesterol was applied to stabilize the membrane of liposomes. The thin film technique in a laboratory scale was a preparation method. The liposomes were then characterized by nanoparticle tracking analysis (NTA), photon correlation spectroscopy (PCS) and light microscopic techniques. The stable liposomes can be produced and the particle sizes after filtration were in nanometers. The 2- and 3-chains-PEG-phospholipid (PL) caused in smaller particle size than the 4-chains-PEG-PL. Liposomes from PL 90G and cholesterol were stable during storage at 8 °C of 56 days because the particle sizes measured by PCS were almost not changed. There was almost no leakage of resveratrol from liposomes PL 90G with cholesterol after diffusion test in dialysis tube for 28 days. All liposomes showed the sustained release during measuring time of 270 min. The maximum release amount of 16-20% was detected with liposomes from 2- and 3-chains-PEG-PL. The other liposomes gave max. release amount of resveratrol only of 10%. The release kinetic can be explained by Korsmeyer-Peppas equation.
Abstract: Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO4) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.
Abstract: Various nanomaterials can be used as a drug delivery
vehicles in nanomedicine, called nanocarriers. They can either be
organic or inorganic, synthetic or natural-based. Although synthetic
nanocarriers are easier to produce, they can often be toxic for the
organism and thus not suitable for use in treatment. From naturalbased
nanocarriers, the most commonly used are protein cages or
viral capsids. In this work, virus bacteriophage λ was used for
delivery of different cytotoxic drugs (cisplatin, carboplatin,
oxaliplatin and doxorubicin). Large quantities of phage λ were
obtained from phage λ-producing strain of E. coli cultivated in
medium with 0.2% maltose. After killing of E. coli with chloroform
and its removal by centrifugation, the phage was concentrated by
ultracentrifugation at 130 000×g and 4°C for 3 h. The encapsulation
of the drugs was performed by infusion method and four different
concentrations of the drugs were encapsulated (200; 100; 50; 25
μg·mL-1). Free drug molecules were removed by filtration. The
encapsulation was verified using the absorbance for doxorubicin and
atomic absorption spectrometry for platinum cytostatics. The amount
of encapsulated drug linearly increased with the increasing
concentration of applied drug with the determination coefficient
R2=0.989 for doxorubicin; R2=0.967 for cisplatin; R2=0.989 for
carboplatin and R2=0.996 for oxaliplatin. The overall encapsulation
efficiency was calculated as 50% for doxorubicin; 8% for cisplatin;
6% for carboplatin and 10% for oxaliplatin.
Abstract: Targeted drug delivery is a method of delivering
medication to a patient in a manner that increases the concentration
of the medication in some parts of the body relative to others.
Targeted drug delivery seeks to concentrate the medication in the
tissues of interest while reducing the relative concentration of the
medication in the remaining tissues. This improves efficacy of the
while reducing side effects. In the present work, we investigate the
effect of magnetic field, flow rate and particle concentration on the
capturing of magnetic particles transported in a stent implanted
fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4)
nanoparticles were synthesized via co-precipitation method. The
synthesized Fe3O4 nanoparticles were added in the de-ionized (DI)
water to prepare the Fe3O4 magnetic particle suspended fluid. This
fluid is transported in a cylindrical tube of diameter 8 mm with help
of a peristaltic pump at different flow rate (25-40 ml/min). A
ferromagnetic coil of SS 430 has been implanted inside the
cylindrical tube to enhance the capturing of magnetic nanoparticles
under magnetic field. The capturing of magnetic nanoparticles was
observed at different magnetic magnetic field, flow rate and particle
concentration. It is observed that capture efficiency increases from
47-67% at magnetic field 2-5kG, respectively at particle
concentration 0.6mg/ml and at flow rate 30 ml/min. However, the
capture efficiency decreases from 65 to 44% by increasing the flow
rate from 25 to 40 ml/min, respectively. Furthermore, it is observed
that capture efficiency increases from 51 to 67% by increasing the
particle concentration from 0.3 to 0.6 mg/ml, respectively.
Abstract: Cancer is still one of the serious diseases threatening
the lives of human beings. How to have an early diagnosis and
effective treatment for tumors is a very important issue. The animal
carcinoma model can provide a simulation tool for the studies of
pathogenesis, biological characteristics, and therapeutic effects.
Recently, drug delivery systems have been rapidly developed to
effectively improve the therapeutic effects. Liposome plays an
increasingly important role in clinical diagnosis and therapy for
delivering a pharmaceutic or contrast agent to the targeted sites.
Liposome can be absorbed and excreted by the human body, and is
well known that no harm to the human body. This study aimed to
compare the therapeutic effects between encapsulated (doxorubicin
liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox)
anti-tumor drugs using magnetic resonance imaging (MRI).
Twenty-four New Zealand rabbits implanted with VX2 carcinoma at
left thighs were classified into three groups: control group (untreated),
Dox-treated group, and LipoDox-treated group, 8 rabbits for each
group. MRI scans were performed three days after tumor implantation.
A 1.5T GE Signa HDxt whole body MRI scanner with a high
resolution knee coil was used in this study. After a 3-plane localizer
scan was performed, three-dimensional (3D) fast spin echo (FSE)
T2-weighted Images (T2WI) was used for tumor volumetric
quantification. Afterwards, two-dimensional (2D) spoiled gradient
recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was
used for tumor perfusion evaluation. DCE-MRI was designed to
acquire four baseline images, followed by contrast agent Gd-DOTA
injection through the ear vein of rabbit. A series of 32 images were
acquired to observe the signals change over time in the tumor and
muscle. The MRI scanning was scheduled on a weekly basis for a
period of four weeks to observe the tumor progression longitudinally.
The Dox and LipoDox treatments were prescribed 3 times in the first
week immediately after the first MRI scan; i.e. 3 days after VX2 tumor
implantation. ImageJ was used to quantitate tumor volume and time
course signal enhancement on DCE images. The changes of tumor size
showed that the growth of VX2 tumors was effectively inhibited for
both LipoDox-treated and Dox-treated groups. Furthermore, the tumor
volume of LipoDox-treated group was significantly lower than that of
Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is
significantly lower than that of the other two groups, which implies
that targeted therapeutic drug remained in the tumor tissue. This study
provides a radiation-free and non-invasive MRI method for
therapeutic monitoring of targeted liposome on an animal tumor
model.
Abstract: It is the patient compliance and stability in
combination with controlled drug delivery and biocompatibility that
forms the core feature in present research and development of
sustained biodegradable patch formulation intended for wound
healing. The aim was to impart sustained degradation, sterile
formulation, significant folding endurance, elasticity,
biodegradability, bio-acceptability and strength. The optimized
formulation comprised of polymers including Hydroxypropyl methyl
cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric
acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric
mixture dissolved in geometric order in suitable medium through
continuous stirring under ambient conditions. With continued stirring
Curcumin was added with aid of DCM and Methanol in optimized
ratio to get homogenous dispersion. The dispersion was sonicated
with optimum frequency and for given time and later casted to form a
patch form. All steps were carried out under strict aseptic conditions.
The formulations obtained in the acceptable working range were
decided based on thickness, uniformity of drug content, smooth
texture and flexibility and brittleness. The patch kept on stability
using butter paper in sterile pack displayed folding endurance in
range of 20 to 23 times without any evidence of crack in an
optimized formulation at room temperature (RT) (24 ± 2°C). The
patch displayed acceptable parameters after stability study conducted
in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) up to 90
days. Further, no significant changes were observed in critical
parameters such as elasticity, biodegradability, drug release and drug
content during stability study conducted at RT 24±2°C for 45 and 90
days. The drug content was in range 95 to 102%, moisture content
didn’t exceeded 19.2% and patch passed the content uniformity test.
Percentage cumulative drug release was found to be 80% in 12h and
matched the biodegradation rate as drug release with correlation
factor R2>0.9. The biodegradable patch based formulation developed
shows promising results in terms of stability and release profiles.
Abstract: Cross-linked konjac glucomannan and kappa
carrageenan film were prepared by chemical crosslinking using
glutaraldehyde (GA) as the crosslinking agent. The effect
crosslinking on the swelling degree was investigated. Konjac
glucomannan and its mixture with kappa carrageenan film was
immersed in GA solution and then thermally cured. The obtained
cross-linked film was washed and soaked in the ethanol to remove
the unreacted GA. The obtained film was air dried at room
temperature to a constant weight. The infrared spectra and the value
of swelling degree of obtained crosslinked film showed that
glucomannan and kappa carrageenan was able to be cross-linked
using glutaraldehyde by film immersion and curing method without
catalyst. The cross-linked films were found to be pH sensitive,
indicating a potential to be used in drug delivery polymer system.
Abstract: Chitosan functionalized Fe3O4-Au core shell
nanoparticles have been prepared using a two-step wet chemical
approach using NaBH4 as reducing agent for formation of Au in
ethylene glycol. X-ray diffraction studies shows individual phases of
Fe3O4 and Au in the as prepared samples with crystallite size of 5.9
and 11.4 nm respectively. The functionalization of the core-shell
nanostructure with Chitosan has been confirmed using Fourier
transform infrared spectroscopy along with signatures of octahedral
and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer
spectroscopy shows decrease in particle-particle interaction in
presence of Au shell (72% sextet) than pure oleic coated Fe3O4
nanoparticles (88% sextet) at room temperature. At 80K, oleic acid
coated Fe3O4 shows only sextets whereas the Chitosan functionalized
Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show
presence of 5 and 11% doublet, respectively.