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: 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: 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: 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: 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: 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: The negative Poisson’s ratios can be described in terms of models based on the geometry of the system and the way this geometry changes due to applied loads. As the Poisson’s ratio does not depend on scale hence deformation can take place at the nano to macro level the only requirement is the right combination of the geometry. Our thrust in this paper is to combine our knowledge of tailored enhanced mechanical properties of the materials having negative Poisson’s ratio with the micromachining and electrospining technology to develop a novel stent carrying a drug delivery system. Therefore, the objective of this paper includes (i) fabrication of a micromachined metal sheet tailored with structure having negative Poisson’s ratio through rotating solid squares geometry using femtosecond laser ablation; (ii) rolling fabricated structure and welding to make a tubular structure (iii) wrapping it with nanofibers of biocompatible polymer PCL (polycaprolactone) for drug delivery (iv) analysis of the functional and mechanical performance of fabricated structure analytically and experimentally. Further, as the applications concerned, tubular structures have potential in biomedical for example hollow tubes called stents are placed inside to provide mechanical support to a damaged artery or diseased region and to open a blocked esophagus thus allowing feeding capacity and improving quality of life.
Abstract: The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.
Abstract: The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 Hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.
Abstract: Floating tablets of Marichyadi Vati were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using HPMC E50 LV act as Matrixing agent, Carbopol as floating enhancer, microcrystalline cellulose as binder, Sodium bi carbonate as effervescent agent with other excipients. The simplex lattice design was used for selection of variables for tablets formulation. Formulation was optimized on the basis of floating time and in vitro drug release. The results showed that the floating lag time for optimized formulation was found to be 61 second with about 97.32 % of total drug release within 3 hours. The vitro release profiles of drug from the formulation could be best expressed zero order with highest linearity r2 = 0.9943. It was concluded that the gastroretentive drug delivery system can be developed for Marichyadi Vati containing Piperine to increase the residence time of the drug in the stomach and thereby increasing bioavailability.
Abstract: The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O2 medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.
Abstract: This study presents design of a carbon silicon electrode
for iontophorsis treatment towards alopecia. The alopecia is a medical
description means loss of hair from the body. For solving this problem,
the drug need to be delivered into the scalp, therefore, the
iontophoresis was chosen to use in this treatment. However, almost
common electrodes of iontophoresis device are made with metal
material, the electrodes could give patients hurt when they using it, and
it is hard to avoid the hair for attaching the hair. For this reason, an
electrode is made with silicon material to decrease the hurt from the
electrodes, and the carbon material is mixed in it for increasing
conductance. The several cones with stainless material on the
electrode make the electrode is able to void hair to attach the affected
part. According to the results of a vivo-experiment, the carbon silicon
electrode showed a good performance and in treatment comfortably.
Abstract: A new and cost effective RP-HPLC method was
developed and validated for simultaneous analysis of non steroidal
anti inflammatory dugs Diclofenac sodium (DFS), Flurbiprofen
(FLP) and an opioid analgesic Tramadol (TMD) in advanced drug
delivery systems (Liposome and Microcapsules), marketed brands
and human plasma. Isocratic system was employed for the flow of
mobile phase consisting of 10 mM sodium dihydrogen phosphate
buffer and acetonitrile in molar ratio of 67: 33 with adjusted pH of
3.2. The stationary phase was hypersil ODS column (C18, 250×4.6
mm i.d., 5 μm) with controlled temperature of 30 C°. DFS in
liposomes, microcapsules and marketed drug products was
determined in range of 99.76-99.84%. FLP and TMD in
microcapsules and brands formulation were 99.78 - 99.94 % and
99.80 - 99.82 %, respectively. Single step liquid-liquid extraction
procedure using combination of acetonitrile and trichloroacetic acid
(TCA) as protein precipitating agent was employed. The detection
limits (at S/N ratio 3) of quality control solutions and plasma samples
were 10, 20, and 20 ng/ml for DFS, FLP and TMD, respectively.
The Assay was acceptable in linear dynamic range. All other
validation parameters were found in limits of FDA and ICH method
validation guidelines. The proposed method is sensitive, accurate and
precise and could be applicable for routine analysis in
pharmaceutical industry as well as in human plasma samples for
bioequivalence and pharmacokinetics studies.
Abstract: This article demonstrated development of
controlled release system of an NSAID drug, Diclofenac
sodium employing different ratios of Ethyl cellulose.
Diclofenac sodium and ethyl cellulose in different proportions
were processed by microencapsulation based on phase
separation technique to formulate microcapsules. The
prepared microcapsules were then compressed into tablets to
obtain controlled release oral formulations. In-vitro evaluation
was performed by dissolution test of each preparation was
conducted in 900 ml of phosphate buffer solution of pH 7.2
maintained at 37 ± 0.5 °C and stirred at 50 rpm. At predetermined
time intervals (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12,
16, 20 and 24 hrs). The drug concentration in the collected
samples was determined by UV spectrophotometer at 276 nm.
The physical characteristics of diclofenac sodium
microcapsules were according to accepted range. These were
off-white, free flowing and spherical in shape. The release
profile of diclofenac sodium from microcapsules was found to
be directly proportional to the proportion of ethylcellulose and
coat thickness. The in-vitro release pattern showed that with
ratio of 1:1 and 1:2 (drug: polymer), the percentage release of
drug at first hour was 16.91 and 11.52 %, respectively as
compared to 1:3 which is only 6.87 % with in this time. The
release mechanism followed higuchi model for its release
pattern. Tablet Formulation (F2) of present study was found
comparable in release profile the marketed brand Phlogin-SR,
microcapsules showed an extended release beyond 24 h.
Further, a good correlation was found between drug release
and proportion of ethylcellulose in the microcapsules.
Microencapsulation based on coacervation found as good
technique to control release of diclofenac sodium for making
the controlled release formulations.
Abstract: Most of the drugs used for pharmaceutical purposes
are poorly water-soluble drugs. About 40% of all newly discovered
drugs are lipophilic and the numbers of lipophilic drugs seem to
increase more and more. Drug delivery systems such as
nanoparticles, micelles or liposomes are applied to improve their
solubility and thus their bioavailability. Besides various techniques of
solubilization, oil-in-water emulsions are often used to incorporate
lipophilic drugs into the oil phase. To stabilize emulsions surface
active substances (surfactants) are generally used. An alternative
method to avoid the application of surfactants was of great interest.
One possibility is to develop O/W-emulsion without any addition of
surface active agents or the so called “surfactant-free emulsion or
SFE”. The aim of this study was to develop and characterize SFE as a
drug carrier by varying the production conditions. Lidocaine base
was used as a model drug. The injection method was developed.
Effects of ultrasound as well as of temperature on the properties of
the emulsion were studied. Particle sizes and release were
determined. The long-term stability up to 30 days was performed.
The results showed that the surfactant-free O/W emulsions with
pharmaceutical oil as drug carrier can be produced.
Abstract: In this article, we synthesize a novel chitosan -based
superabsorbent hydrogel via graft copolymerization of mixtures
acrylic acid (AA) and N-vinyl pyrollidon onto chitosan backbones.
The polymerization reaction was carried out in an aqueous medium
and in the presence of ammonium persulfate (APS) as an initiator and
N,N'-methylene bisacrylamide (MBA) as a crosslinker.The hydrogel
structures were confirmed by FTIR spectroscopy. The swelling
behavior of these absorbent polymers was also investigated in
various salt solutions. Results indicated that the swelling capacity
decreased with an increase in the ionic strength of the swelling
medium. Furthermore, the swelling of superabsorbing hydrogels was
examined in solutions with pH values ranging between 1.0 and 13.0.
It showed a reversible pH-responsive behavior at pHs 2.0 and 8.0.
This on-off switching behavior makes the synthesized hydrogels as
an excellent candidate for controlled delivery of bioactive agents.
Abstract: Herein, we report the different types of surface morphology due to the interaction between the pure protein Insulin (INS) and catanionic surfactant mixture of Sodium Dodecyl Sulfate (SDS) and Cetyl Trimethyl Ammonium Bromide (CTAB) at air/water interface obtained by the Langmuir-Blodgett (LB) technique. We characterized the aggregations by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) in LB films. We found that the INS adsorption increased in presence of catanionic surfactant at air/water interface. The presence of small amount of surfactant induces two-stage growth kinetics due to the pure protein absorption and protein-catanionic surface micelle interaction. The protein remains in native state in presence of small amount of surfactant mixture. Smaller amount of surfactant mixture with INS is producing surface micelle type structure. This may be considered for drug delivery system. On the other hand, INS becomes unfolded and fibrillated in presence of higher amount of surfactant mixture. In both the cases, the protein was successfully immobilized on a glass substrate by the LB technique. These results may find applications in the fundamental science of the physical chemistry of surfactant systems, as well as in the preparation of drug-delivery system.
Abstract: Carbon nanotubes (CNTs) with their high mechanical,
electrical, thermal and chemical properties are regarded as promising
materials for many different potential applications. Having unique
properties they can be used in a wide range of fields such as
electronic devices, electrodes, drug delivery systems, hydrogen
storage, textile etc. Catalytic chemical vapor deposition (CCVD) is a
common method for CNT production especially for mass production.
Catalysts impregnated on a suitable substrate are important for
production with chemical vapor deposition (CVD) method. Iron
catalyst and MgO substrate is one of most common catalyst-substrate
combination used for CNT. In this study, CNTs were produced by
CCVD of acetylene (C2H2) on magnesium oxide (MgO) powder
substrate impregnated by iron nitrate (Fe(NO3)3•9H2O) solution. The
CNT synthesis conditions were as follows: at synthesis temperatures
of 500 and 800°C multiwall and single wall CNTs were produced
respectively. Iron (Fe) catalysts were prepared by with Fe:MgO ratio
of 1:100, 5:100 and 10:100. The duration of syntheses were 30 and
60 minutes for all temperatures and catalyst percentages. The
synthesized materials were characterized by thermal gravimetric
analysis (TGA), transmission electron microscopy (TEM) and Raman
spectroscopy.